<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01661595</url>
  </required_header>
  <id_info>
    <org_study_id>12-153</org_study_id>
    <nct_id>NCT01661595</nct_id>
  </id_info>
  <brief_title>The Effect of Sildenafil and Tadalafil on Skeletal Muscle and Perceptual Fatigue</brief_title>
  <official_title>The Effect of Sildenafil and Tadalafil on Skeletal Muscle and Perceptual Fatigue.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Texas Medical Branch, Galveston</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Texas Medical Branch, Galveston</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is funded by the Moody Endowment. In this project, we will investigate the&#xD;
      potential effect of skeletal muscle nitric oxide (NO) production on skeletal muscle&#xD;
      anabolism, muscle strength, physical function, and body composition in older individuals.&#xD;
      Further, we will determine whether augmentation of NO-mediated signaling reduces fatigue and&#xD;
      fatigability.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The Investigators hypothesize that upregulation of skeletal muscle NO-cGMP mediated responses&#xD;
      through phosphodiesterase (PDE) inhibition by sildenafil or tadalafil causes an acute&#xD;
      anabolic response of skeletal muscle protein synthesis. NO is well-known to elicit&#xD;
      vasodilation through stimulation of cGMP signaling, and NO-mediated changes in muscle&#xD;
      perfusion may influence both skeletal muscle anabolism and perceptual fatigue. To measure&#xD;
      skeletal muscle protein synthesis, we will infuse a stable isotope tracer of phenylalanine&#xD;
      and measure its incorporation into skeletal muscle proteins following a dose of sildenafil,&#xD;
      tadalafil, or placebo. The Investigators will also determine whether differences exist&#xD;
      between men and women in response to PDE inhibition. As skeletal muscle NO-cGMP signaling has&#xD;
      been implicated in fatigue responses, we will assess the acute effect of sildenafil and&#xD;
      tadalafil on fatigue. Fatigue can be manifested both as a performance deficit at a local&#xD;
      level (e.g., a reduced ability of skeletal muscle to produce power or force) as well as a&#xD;
      subjective experience of lacking physical or mental energy. Accordingly, we will use more&#xD;
      than one means (skeletal muscle performance, fatigue questionnaires, accelerometers) to study&#xD;
      fatigue. The Investigators hypothesize that sildenafil or tadalafil will acutely reduce&#xD;
      exercise-associated fatigability and skeletal muscle fatigue development&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Subjects were assigned to one of 4 arms:&#xD;
Sildenafil (50mg/day) for weeks 0-4. Placebo for weeks 5-8.&#xD;
Tadalafil (10mg/day) for weeks 0-4. Placebo for weeks 5-8.&#xD;
Placebo for weeks 0-4. Sildenafil (50mg/day) for weeks 5-8.&#xD;
Placebo for weeks 0-4. Tadalafil (10mg/day) for weeks 5-8.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Skeletal Muscle Fatigue as Measured by Biodex 4 Pro After 4 Weeks of Placebo</measure>
    <time_frame>after 4 weeks of placebo</time_frame>
    <description>Isokinetic Fatigue Measure (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 50 contractions were performed at 100% force, one contraction every second. Isokinetic fatigue will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug. Data is presented as mean maximum force over all 50 kicks.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Skeletal Muscle Fatigue as Measured by Biodex 4 Pro After 4 Weeks of Active Drug</measure>
    <time_frame>after 4 weeks of active drug</time_frame>
    <description>Isokinetic Fatigue Measure (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 50 contractions were performed at 100% force, one contraction every second. Isokinetic fatigue will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug. Data is presented as mean maximum force over all 50 kicks.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Exercised Induced Fatigability as Measured by Fatigue Rating Scale After 4 Weeks of Placebo</measure>
    <time_frame>after 4 weeks of placebo</time_frame>
    <description>The fatigue rating scale is a scale from 0 to 10 with 0 being no fatigue at all and 10 being the worst fatigue the subject can imagine. The subject is asked to rate their level of fatigue in their leg. This test was performed before and immedicately after the Biodex leg fatigue test after 4 weeks of placebo. Data is presented as change in scale from pre fatigue test to post fatigue test, with a higher score indicating a greater level of fatigue.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Exercised Induced Fatigability as Measured by Fatigue Rating Scale After 4 Weeks of Active Drug</measure>
    <time_frame>after 4 weeks of active drug</time_frame>
    <description>The fatigue rating scale is a scale from 0 to 10 with 0 being no fatigue at all and 10 being the worst fatigue the subject can imagine. The subject is asked to rate their level of fatigue in their leg. This test was performed before and immedicately after the Biodex leg fatigue test. Data is presented as change in scale from pre fatigue test to post fatigue test, with a higher score indicating a greater level of fatigue.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Placebo</measure>
    <time_frame>after 4 weeks of placebo</time_frame>
    <description>Peak isometric strength is measured on a Biodex System 4 Pro. This test is isolated to the quadricep muscle of one leg. Isometric test is performed at 90 degrees with 5 seconds of force production for each contraction and 15 seconds of rest. 1 set of 3 contractions at 100% force performed. Isometric strength was measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Active Drug.</measure>
    <time_frame>after 4 weeks of active drug</time_frame>
    <description>Peak isometric strength is measured on a Biodex System 4 Pro. This test is isolated to the quadricep muscle of one leg. Isometric test is performed at 90 degrees with 5 seconds of force production for each contraction and 15 seconds of rest. 1 set of 3 contractions at 100% force performed. Isometric strength was measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Placebo.</measure>
    <time_frame>after 4 weeks of placebo</time_frame>
    <description>Isokinetic strength (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 1 set of 3 contractions were performed at 100% force. Isokinetic strength will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Active Drug</measure>
    <time_frame>after 4 weeks of active drug</time_frame>
    <description>Isokinetic strength (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 1 set of 3 contractions were performed at 100% force. Isokinetic strength will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 0.</measure>
    <time_frame>week 0</time_frame>
    <description>Lean Body Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 4.</measure>
    <time_frame>week 4</time_frame>
    <description>Lean Body Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 8.</measure>
    <time_frame>week 8</time_frame>
    <description>Lean Body Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 0.</measure>
    <time_frame>week 0</time_frame>
    <description>Fat Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 4.</measure>
    <time_frame>week 4</time_frame>
    <description>Fat Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 8.</measure>
    <time_frame>week 8</time_frame>
    <description>Fat Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Walking Distance at 100% Effort as Measured by Walking Test After 4 Weeks of Placebo</measure>
    <time_frame>after 4 weeks of placebo</time_frame>
    <description>Walking performance will be assessed during 2 minutes of walking in long corridor hallways. Subjects will be asked to walk at 100% effort (as quickly as they can safely walk without running) for 2 minutes. Distance traveled for the 2 minutes will be recorded. The walking test will be completed at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Walking Distance at 100% Effort as Measured by Walking Test After 4 Weeks of Active Drug</measure>
    <time_frame>after 4 weeks of active drug</time_frame>
    <description>Walking performance will be assessed during 2 minutes of walking in long corridor hallways. Subjects will be asked to walk at 100% effort (as quickly as they can safely walk without running) for 2 minutes. Distance traveled for the 2 minutes will be recorded. The walking test will be completed at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 0</measure>
    <time_frame>Week 0</time_frame>
    <description>Fatigue symptoms will be measured using the 30-item Multidimensional Fatigue Symptom Inventory - Short Form, a validated measure that yields one overall score of total fatigue calculated using five sub scales (general, physical, emotional, mental, vigor). With the exception of the vigor sub scale, higher scores indicate greater fatigue. Total fatigue score is calculated by summing the sub categories (general, physical, emotional and mental) and subtracting vigor. Total scores range from -24 to 96, with a higher score indicating more fatigue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 4</measure>
    <time_frame>week 4</time_frame>
    <description>Fatigue symptoms will be measured using the 30-item Multidimensional Fatigue Symptom Inventory - Short Form, a validated measure that yields one overall score of total fatigue calculated using five sub scales (general, physical, emotional, mental, vigor). With the exception of the vigor sub scale, higher scores indicate greater fatigue. Total fatigue score is calculated by summing the sub categories (general, physical, emotional and mental) and subtracting vigor. Total scores range from -24 to 96, with a higher score indicating more fatigue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 8</measure>
    <time_frame>week 8</time_frame>
    <description>Fatigue symptoms will be measured using the 30-item Multidimensional Fatigue Symptom Inventory - Short Form, a validated measure that yields one overall score of total fatigue calculated using five sub scales (general, physical, emotional, mental, vigor). With the exception of the vigor sub scale, higher scores indicate greater fatigue. Total fatigue score is calculated by summing the sub categories (general, physical, emotional and mental) and subtracting vigor. Total scores range from -24 to 96, with a higher score indicating more fatigue.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Hemoglobin Level at Week 0</measure>
    <time_frame>week 0</time_frame>
    <description>Hemoglobin was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 11.6 - 15.0 g/dL.</description>
  </other_outcome>
  <other_outcome>
    <measure>Hemoglobin Level Measured at Week 4</measure>
    <time_frame>week 4</time_frame>
    <description>Hemoglobin was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 11.6 - 15.0 g/dL.</description>
  </other_outcome>
  <other_outcome>
    <measure>Hemoglobin Level Measured at Week 8</measure>
    <time_frame>week 8</time_frame>
    <description>Hemoglobin was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 11.6 - 15.0 g/dL.</description>
  </other_outcome>
  <other_outcome>
    <measure>Hematocrit Level Measured at Week 0</measure>
    <time_frame>week 0</time_frame>
    <description>Hematocrit was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 35.7 - 45.2%.</description>
  </other_outcome>
  <other_outcome>
    <measure>Hematocrit Level Was Measured at 4 Weeks</measure>
    <time_frame>4 weeks</time_frame>
    <description>Hematocrit was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 35.7 - 45.2%.</description>
  </other_outcome>
  <other_outcome>
    <measure>Hematocrit Level Measured at Week 8</measure>
    <time_frame>week 8</time_frame>
    <description>Hematocrit was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 35.7 - 45.2%.</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Fatigue</condition>
  <arm_group>
    <arm_group_label>Sildenafil / Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 0-4. Placebo for weeks 5-8.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tadalafil / Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 0-4. Placebo for weeks 5-8.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo / Sildenafil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Placebo for weeks 0-4. 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 5-8.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo / Tadalafil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Placebo for weeks 0-4. 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 5-8.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sildenafil</intervention_name>
    <description>50 mg/day for 4 weeks</description>
    <arm_group_label>Placebo / Sildenafil</arm_group_label>
    <arm_group_label>Sildenafil / Placebo</arm_group_label>
    <other_name>Viagra</other_name>
    <other_name>Revatio</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>tadalafil</intervention_name>
    <description>10 mg/day for 4 weeks.</description>
    <arm_group_label>Placebo / Tadalafil</arm_group_label>
    <arm_group_label>Tadalafil / Placebo</arm_group_label>
    <other_name>Cialis</other_name>
    <other_name>Adcirca</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo 1 capsule per day for four weeks.</description>
    <arm_group_label>Placebo / Sildenafil</arm_group_label>
    <arm_group_label>Placebo / Tadalafil</arm_group_label>
    <arm_group_label>Sildenafil / Placebo</arm_group_label>
    <arm_group_label>Tadalafil / Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 50-60 years of age&#xD;
&#xD;
          2. Ability to sign consent form (score&gt;23 on the 30-item Mini Mental Status examination,&#xD;
             MMSE)&#xD;
&#xD;
          3. Stable body weight for at least three months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Physical dependence or frailty (impairment in any of the Activities of Daily Living&#xD;
             (ADL), history of falls (&gt;2/year) or significant weight loss in the past year).&#xD;
&#xD;
          2. Pregnancy&#xD;
&#xD;
          3. Significant heart, liver, kidney, blood or respiratory disease.&#xD;
&#xD;
          4. Peripheral vascular disease.&#xD;
&#xD;
          5. Diabetes mellitus or other untreated endocrine disease.&#xD;
&#xD;
          6. Active cancer&#xD;
&#xD;
          7. Use of nitrates.&#xD;
&#xD;
          8. Recent (within 6 months) treatment with anabolic steroids, or corticosteroids.&#xD;
&#xD;
          9. Alcohol or drug abuse.&#xD;
&#xD;
         10. Severe depression (&gt;5 on the 15-item Geriatric Depression Scale, GDS).&#xD;
&#xD;
         11. Cardiac abnormalities such as cardiac shunt or previously diagnosed pulmonary&#xD;
             hypertension.&#xD;
&#xD;
         12. Systolic blood pressure &lt;100 or&gt;150, diastolic blood pressure &lt;60 or 90&gt;. This range&#xD;
             is smaller than the acceptable range stated in the prescribing information for&#xD;
             sildenafil/tadalafil (90/50 and &lt;170/110).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Melinda Sheffield-Moore, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas Medical Branch, Galveston</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas Medical Branch</name>
      <address>
        <city>Galveston</city>
        <state>Texas</state>
        <zip>77555-0361</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <results_first_submitted>April 24, 2018</results_first_submitted>
  <results_first_submitted_qc>June 19, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">July 17, 2018</results_first_posted>
  <last_update_submitted>June 19, 2018</last_update_submitted>
  <last_update_submitted_qc>June 19, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fatigue</keyword>
  <keyword>Fatigability</keyword>
  <keyword>Surface Electromyography (sEMG)</keyword>
  <keyword>cyclic guanosine monophosphate (cGMP)</keyword>
  <keyword>Nitric Oxide (NO)</keyword>
  <keyword>NO-cGMP</keyword>
  <keyword>Phosphodiesterase (PDE)</keyword>
  <keyword>Sildenafil</keyword>
  <keyword>Tadalafil</keyword>
  <keyword>Isotope</keyword>
  <keyword>Infusion</keyword>
  <keyword>Anabolism</keyword>
  <keyword>Upregulation</keyword>
  <keyword>Accelerometer</keyword>
  <keyword>Placebo</keyword>
  <keyword>Nitrosylation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fatigue</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sildenafil Citrate</mesh_term>
    <mesh_term>Tadalafil</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited from the community via flyers and local postings.</recruitment_details>
      <pre_assignment_details>30 subjects enrolled in this study. 6 subjects failed the screening and were withdrawn. 6 subjects chose to withdraw participation before the study began. 18 subjects began the study. 2 subjects were withdrawn during the study. 16 subjects completed the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Sildenafil, Then Placebo</title>
          <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
        </group>
        <group group_id="P2">
          <title>Tadalfil, Then Placebo</title>
          <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
        </group>
        <group group_id="P3">
          <title>Placebo, Then Sildenafil</title>
          <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
        </group>
        <group group_id="P4">
          <title>Placebo, Then Tadalafil</title>
          <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Phase 1: Week 0-4</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Phase 2: Week 5-8.</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>30 subjects enrolled in this study. 6 subjects failed the screening and were withdrawn. 6 subjects chose to withdraw participation before the study began. 18 subjects began the study. 2 subjects were withdrawn during the study. 16 subjects completed the study.</population>
      <group_list>
        <group group_id="B1">
          <title>Sildenafil, Then Placebo</title>
          <description>Sildenafil (50mg/day) daily for weeks 0-4, then Placebo daily weeks 5-8.</description>
        </group>
        <group group_id="B2">
          <title>Tadalfil, Then Placebo</title>
          <description>Tadalafil (10mg/day) daily for weeks 0-4, then Placebo daily for weeks 5-8.</description>
        </group>
        <group group_id="B3">
          <title>Placebo, Then Sildenafil</title>
          <description>Placebo daily for weeks 0-4, then Sildenafil (50mg/day) daily for weeks 5-8.</description>
        </group>
        <group group_id="B4">
          <title>Placebo, Then Tadalafil</title>
          <description>Placebo daily for weeks 0-4, then Tadalafil (10mg/day) daily for weeks 5-8.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="5"/>
            <count group_id="B4" value="4"/>
            <count group_id="B5" value="18"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53.6" spread="4.16"/>
                    <measurement group_id="B2" value="56" spread="1.41"/>
                    <measurement group_id="B3" value="52.4" spread="1.51"/>
                    <measurement group_id="B4" value="57.25" spread="2.99"/>
                    <measurement group_id="B5" value="54.6" spread="3.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Skeletal Muscle Fatigue as Measured by Biodex 4 Pro After 4 Weeks of Placebo</title>
        <description>Isokinetic Fatigue Measure (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 50 contractions were performed at 100% force, one contraction every second. Isokinetic fatigue will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug. Data is presented as mean maximum force over all 50 kicks.</description>
        <time_frame>after 4 weeks of placebo</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 0-4. Placebo for weeks 5-8.&#xD;
Sildenafil: 50 mg/day for 4 weeks&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tadalafil, Then Placebo</title>
            <description>10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 0-4. Placebo for weeks 5-8.&#xD;
tadalafil: 10 mg/day for 4 weeks.&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo for weeks 0-4. 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 5-8.&#xD;
Sildenafil: 50 mg/day for 4 weeks&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for weeks 0-4. 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 5-8.&#xD;
tadalafil: 10 mg/day for 4 weeks.&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Skeletal Muscle Fatigue as Measured by Biodex 4 Pro After 4 Weeks of Placebo</title>
          <description>Isokinetic Fatigue Measure (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 50 contractions were performed at 100% force, one contraction every second. Isokinetic fatigue will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug. Data is presented as mean maximum force over all 50 kicks.</description>
          <units>Newton-Meters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.69" spread="33.71"/>
                    <measurement group_id="O2" value="42.07" spread="5.19"/>
                    <measurement group_id="O3" value="67.17" spread="26.87"/>
                    <measurement group_id="O4" value="63.24" spread="8.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Skeletal Muscle Fatigue as Measured by Biodex 4 Pro After 4 Weeks of Active Drug</title>
        <description>Isokinetic Fatigue Measure (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 50 contractions were performed at 100% force, one contraction every second. Isokinetic fatigue will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug. Data is presented as mean maximum force over all 50 kicks.</description>
        <time_frame>after 4 weeks of active drug</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil / Placebo</title>
            <description>50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 0-4. Placebo for weeks 5-8.&#xD;
Sildenafil: 50 mg/day for 4 weeks&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tadalafil / Placebo</title>
            <description>10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 0-4. Placebo for weeks 5-8.&#xD;
tadalafil: 10 mg/day for 4 weeks.&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
          <group group_id="O3">
            <title>Placebo / Sildenafil</title>
            <description>Placebo for weeks 0-4. 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 5-8.&#xD;
Sildenafil: 50 mg/day for 4 weeks&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo / Tadalafil</title>
            <description>Placebo for weeks 0-4. 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 5-8.&#xD;
tadalafil: 10 mg/day for 4 weeks.&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Skeletal Muscle Fatigue as Measured by Biodex 4 Pro After 4 Weeks of Active Drug</title>
          <description>Isokinetic Fatigue Measure (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 50 contractions were performed at 100% force, one contraction every second. Isokinetic fatigue will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug. Data is presented as mean maximum force over all 50 kicks.</description>
          <units>Newton-Meters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.90" spread="35.60"/>
                    <measurement group_id="O2" value="42.48" spread="6.30"/>
                    <measurement group_id="O3" value="62.68" spread="24.88"/>
                    <measurement group_id="O4" value="63.25" spread="15.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Exercised Induced Fatigability as Measured by Fatigue Rating Scale After 4 Weeks of Placebo</title>
        <description>The fatigue rating scale is a scale from 0 to 10 with 0 being no fatigue at all and 10 being the worst fatigue the subject can imagine. The subject is asked to rate their level of fatigue in their leg. This test was performed before and immedicately after the Biodex leg fatigue test after 4 weeks of placebo. Data is presented as change in scale from pre fatigue test to post fatigue test, with a higher score indicating a greater level of fatigue.</description>
        <time_frame>after 4 weeks of placebo</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil / Placebo</title>
            <description>50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 0-4. Placebo for weeks 5-8.&#xD;
Sildenafil: 50 mg/day for 4 weeks&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tadalafil / Placebo</title>
            <description>10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 0-4. Placebo for weeks 5-8.&#xD;
tadalafil: 10 mg/day for 4 weeks.&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
          <group group_id="O3">
            <title>Placebo / Sildenafil</title>
            <description>Placebo for weeks 0-4. 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 5-8.&#xD;
Sildenafil: 50 mg/day for 4 weeks&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo / Tadalafil</title>
            <description>Placebo for weeks 0-4. 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 5-8.&#xD;
tadalafil: 10 mg/day for 4 weeks.&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Exercised Induced Fatigability as Measured by Fatigue Rating Scale After 4 Weeks of Placebo</title>
          <description>The fatigue rating scale is a scale from 0 to 10 with 0 being no fatigue at all and 10 being the worst fatigue the subject can imagine. The subject is asked to rate their level of fatigue in their leg. This test was performed before and immedicately after the Biodex leg fatigue test after 4 weeks of placebo. Data is presented as change in scale from pre fatigue test to post fatigue test, with a higher score indicating a greater level of fatigue.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.33" spread="1.53"/>
                    <measurement group_id="O2" value="2.5" spread="0.58"/>
                    <measurement group_id="O3" value="7.0" spread="1.83"/>
                    <measurement group_id="O4" value="4.75" spread="0.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Exercised Induced Fatigability as Measured by Fatigue Rating Scale After 4 Weeks of Active Drug</title>
        <description>The fatigue rating scale is a scale from 0 to 10 with 0 being no fatigue at all and 10 being the worst fatigue the subject can imagine. The subject is asked to rate their level of fatigue in their leg. This test was performed before and immedicately after the Biodex leg fatigue test. Data is presented as change in scale from pre fatigue test to post fatigue test, with a higher score indicating a greater level of fatigue.</description>
        <time_frame>after 4 weeks of active drug</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil / Placebo</title>
            <description>50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 0-4. Placebo for weeks 5-8.&#xD;
Sildenafil: 50 mg/day for 4 weeks&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tadalafil / Placebo</title>
            <description>10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 0-4. Placebo for weeks 5-8.&#xD;
tadalafil: 10 mg/day for 4 weeks.&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
          <group group_id="O3">
            <title>Placebo / Sildenafil</title>
            <description>Placebo for weeks 0-4. 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 5-8.&#xD;
Sildenafil: 50 mg/day for 4 weeks&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo / Tadalafil</title>
            <description>Placebo for weeks 0-4. 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 5-8.&#xD;
tadalafil: 10 mg/day for 4 weeks.&#xD;
Placebo: Placebo 1 capsule per day for four weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Exercised Induced Fatigability as Measured by Fatigue Rating Scale After 4 Weeks of Active Drug</title>
          <description>The fatigue rating scale is a scale from 0 to 10 with 0 being no fatigue at all and 10 being the worst fatigue the subject can imagine. The subject is asked to rate their level of fatigue in their leg. This test was performed before and immedicately after the Biodex leg fatigue test. Data is presented as change in scale from pre fatigue test to post fatigue test, with a higher score indicating a greater level of fatigue.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" spread="2.38"/>
                    <measurement group_id="O2" value="3.5" spread="1.73"/>
                    <measurement group_id="O3" value="5.25" spread="4.27"/>
                    <measurement group_id="O4" value="6.0" spread="1.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Placebo</title>
        <description>Peak isometric strength is measured on a Biodex System 4 Pro. This test is isolated to the quadricep muscle of one leg. Isometric test is performed at 90 degrees with 5 seconds of force production for each contraction and 15 seconds of rest. 1 set of 3 contractions at 100% force performed. Isometric strength was measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
        <time_frame>after 4 weeks of placebo</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Placebo</title>
          <description>Peak isometric strength is measured on a Biodex System 4 Pro. This test is isolated to the quadricep muscle of one leg. Isometric test is performed at 90 degrees with 5 seconds of force production for each contraction and 15 seconds of rest. 1 set of 3 contractions at 100% force performed. Isometric strength was measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
          <units>Newton-Meters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="145.86" spread="97.73"/>
                    <measurement group_id="O2" value="104.17" spread="23.66"/>
                    <measurement group_id="O3" value="149.14" spread="62.67"/>
                    <measurement group_id="O4" value="148.34" spread="47.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Active Drug.</title>
        <description>Peak isometric strength is measured on a Biodex System 4 Pro. This test is isolated to the quadricep muscle of one leg. Isometric test is performed at 90 degrees with 5 seconds of force production for each contraction and 15 seconds of rest. 1 set of 3 contractions at 100% force performed. Isometric strength was measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
        <time_frame>after 4 weeks of active drug</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Active Drug.</title>
          <description>Peak isometric strength is measured on a Biodex System 4 Pro. This test is isolated to the quadricep muscle of one leg. Isometric test is performed at 90 degrees with 5 seconds of force production for each contraction and 15 seconds of rest. 1 set of 3 contractions at 100% force performed. Isometric strength was measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
          <units>Newton-Meters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="140.09" spread="82.29"/>
                    <measurement group_id="O2" value="110.39" spread="21.26"/>
                    <measurement group_id="O3" value="133.81" spread="58.04"/>
                    <measurement group_id="O4" value="139.96" spread="50.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Placebo.</title>
        <description>Isokinetic strength (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 1 set of 3 contractions were performed at 100% force. Isokinetic strength will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
        <time_frame>after 4 weeks of placebo</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Placebo.</title>
          <description>Isokinetic strength (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 1 set of 3 contractions were performed at 100% force. Isokinetic strength will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
          <units>Newton-Meters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="105.15" spread="49.46"/>
                    <measurement group_id="O2" value="78.59" spread="10.25"/>
                    <measurement group_id="O3" value="117.71" spread="39.86"/>
                    <measurement group_id="O4" value="111.67" spread="23.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Active Drug</title>
        <description>Isokinetic strength (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 1 set of 3 contractions were performed at 100% force. Isokinetic strength will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
        <time_frame>after 4 weeks of active drug</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Active Drug</title>
          <description>Isokinetic strength (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 1 set of 3 contractions were performed at 100% force. Isokinetic strength will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
          <units>Newton-Meters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="106.79" spread="49.69"/>
                    <measurement group_id="O2" value="79.33" spread="11.69"/>
                    <measurement group_id="O3" value="116.48" spread="37.83"/>
                    <measurement group_id="O4" value="114.75" spread="36.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 0.</title>
        <description>Lean Body Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
        <time_frame>week 0</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 0.</title>
          <description>Lean Body Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
          <units>kilograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.60" spread="11.62"/>
                    <measurement group_id="O2" value="41.43" spread="4.72"/>
                    <measurement group_id="O3" value="49.93" spread="10.63"/>
                    <measurement group_id="O4" value="54.45" spread="14.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 4.</title>
        <description>Lean Body Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
        <time_frame>week 4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 4.</title>
          <description>Lean Body Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
          <units>kilograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.29" spread="14.40"/>
                    <measurement group_id="O2" value="41.02" spread="4.05"/>
                    <measurement group_id="O3" value="50.61" spread="10.67"/>
                    <measurement group_id="O4" value="54.85" spread="14.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 8.</title>
        <description>Lean Body Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
        <time_frame>week 8</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 8.</title>
          <description>Lean Body Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
          <units>kilograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.22" spread="14.68"/>
                    <measurement group_id="O2" value="40.76" spread="4.38"/>
                    <measurement group_id="O3" value="52.09" spread="10.03"/>
                    <measurement group_id="O4" value="55.10" spread="14.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 0.</title>
        <description>Fat Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
        <time_frame>week 0</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 0.</title>
          <description>Fat Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
          <units>kilograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.35" spread="11.40"/>
                    <measurement group_id="O2" value="37.21" spread="6.81"/>
                    <measurement group_id="O3" value="32.72" spread="5.92"/>
                    <measurement group_id="O4" value="32.10" spread="6.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 4.</title>
        <description>Fat Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
        <time_frame>week 4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 4.</title>
          <description>Fat Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
          <units>kilograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.16" spread="12.42"/>
                    <measurement group_id="O2" value="37.12" spread="6.35"/>
                    <measurement group_id="O3" value="32.30" spread="5.55"/>
                    <measurement group_id="O4" value="32.47" spread="7.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 8.</title>
        <description>Fat Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
        <time_frame>week 8</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 8.</title>
          <description>Fat Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.</description>
          <units>kilograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.60" spread="12.51"/>
                    <measurement group_id="O2" value="37.02" spread="6.21"/>
                    <measurement group_id="O3" value="32.40" spread="5.83"/>
                    <measurement group_id="O4" value="32.79" spread="7.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Walking Distance at 100% Effort as Measured by Walking Test After 4 Weeks of Placebo</title>
        <description>Walking performance will be assessed during 2 minutes of walking in long corridor hallways. Subjects will be asked to walk at 100% effort (as quickly as they can safely walk without running) for 2 minutes. Distance traveled for the 2 minutes will be recorded. The walking test will be completed at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
        <time_frame>after 4 weeks of placebo</time_frame>
        <population>1 subject did not complete the walking test</population>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Walking Distance at 100% Effort as Measured by Walking Test After 4 Weeks of Placebo</title>
          <description>Walking performance will be assessed during 2 minutes of walking in long corridor hallways. Subjects will be asked to walk at 100% effort (as quickly as they can safely walk without running) for 2 minutes. Distance traveled for the 2 minutes will be recorded. The walking test will be completed at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
          <population>1 subject did not complete the walking test</population>
          <units>meters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="203.82" spread="30.51"/>
                    <measurement group_id="O2" value="189.79" spread="38.12"/>
                    <measurement group_id="O3" value="198.41" spread="14.04"/>
                    <measurement group_id="O4" value="202.80" spread="37.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Walking Distance at 100% Effort as Measured by Walking Test After 4 Weeks of Active Drug</title>
        <description>Walking performance will be assessed during 2 minutes of walking in long corridor hallways. Subjects will be asked to walk at 100% effort (as quickly as they can safely walk without running) for 2 minutes. Distance traveled for the 2 minutes will be recorded. The walking test will be completed at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
        <time_frame>after 4 weeks of active drug</time_frame>
        <population>1 subject did not complete the walking test.</population>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Walking Distance at 100% Effort as Measured by Walking Test After 4 Weeks of Active Drug</title>
          <description>Walking performance will be assessed during 2 minutes of walking in long corridor hallways. Subjects will be asked to walk at 100% effort (as quickly as they can safely walk without running) for 2 minutes. Distance traveled for the 2 minutes will be recorded. The walking test will be completed at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.</description>
          <population>1 subject did not complete the walking test.</population>
          <units>meter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="197.01" spread="32.72"/>
                    <measurement group_id="O2" value="178.56" spread="17.84"/>
                    <measurement group_id="O3" value="200.19" spread="13.99"/>
                    <measurement group_id="O4" value="203.46" spread="31.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 0</title>
        <description>Fatigue symptoms will be measured using the 30-item Multidimensional Fatigue Symptom Inventory - Short Form, a validated measure that yields one overall score of total fatigue calculated using five sub scales (general, physical, emotional, mental, vigor). With the exception of the vigor sub scale, higher scores indicate greater fatigue. Total fatigue score is calculated by summing the sub categories (general, physical, emotional and mental) and subtracting vigor. Total scores range from -24 to 96, with a higher score indicating more fatigue.</description>
        <time_frame>Week 0</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 0</title>
          <description>Fatigue symptoms will be measured using the 30-item Multidimensional Fatigue Symptom Inventory - Short Form, a validated measure that yields one overall score of total fatigue calculated using five sub scales (general, physical, emotional, mental, vigor). With the exception of the vigor sub scale, higher scores indicate greater fatigue. Total fatigue score is calculated by summing the sub categories (general, physical, emotional and mental) and subtracting vigor. Total scores range from -24 to 96, with a higher score indicating more fatigue.</description>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.66" spread="19.55"/>
                    <measurement group_id="O2" value="-7.5" spread="5.45"/>
                    <measurement group_id="O3" value="-8" spread="3.61"/>
                    <measurement group_id="O4" value="-3.75" spread="9.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 4</title>
        <description>Fatigue symptoms will be measured using the 30-item Multidimensional Fatigue Symptom Inventory - Short Form, a validated measure that yields one overall score of total fatigue calculated using five sub scales (general, physical, emotional, mental, vigor). With the exception of the vigor sub scale, higher scores indicate greater fatigue. Total fatigue score is calculated by summing the sub categories (general, physical, emotional and mental) and subtracting vigor. Total scores range from -24 to 96, with a higher score indicating more fatigue.</description>
        <time_frame>week 4</time_frame>
        <population>1 subject did not complete the week 4 MFSI questionnaire</population>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 4</title>
          <description>Fatigue symptoms will be measured using the 30-item Multidimensional Fatigue Symptom Inventory - Short Form, a validated measure that yields one overall score of total fatigue calculated using five sub scales (general, physical, emotional, mental, vigor). With the exception of the vigor sub scale, higher scores indicate greater fatigue. Total fatigue score is calculated by summing the sub categories (general, physical, emotional and mental) and subtracting vigor. Total scores range from -24 to 96, with a higher score indicating more fatigue.</description>
          <population>1 subject did not complete the week 4 MFSI questionnaire</population>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.33" spread="26.08"/>
                    <measurement group_id="O2" value="-3.33" spread="10.97"/>
                    <measurement group_id="O3" value="-6.33" spread="2.31"/>
                    <measurement group_id="O4" value="-3.5" spread="12.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 8</title>
        <description>Fatigue symptoms will be measured using the 30-item Multidimensional Fatigue Symptom Inventory - Short Form, a validated measure that yields one overall score of total fatigue calculated using five sub scales (general, physical, emotional, mental, vigor). With the exception of the vigor sub scale, higher scores indicate greater fatigue. Total fatigue score is calculated by summing the sub categories (general, physical, emotional and mental) and subtracting vigor. Total scores range from -24 to 96, with a higher score indicating more fatigue.</description>
        <time_frame>week 8</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 8</title>
          <description>Fatigue symptoms will be measured using the 30-item Multidimensional Fatigue Symptom Inventory - Short Form, a validated measure that yields one overall score of total fatigue calculated using five sub scales (general, physical, emotional, mental, vigor). With the exception of the vigor sub scale, higher scores indicate greater fatigue. Total fatigue score is calculated by summing the sub categories (general, physical, emotional and mental) and subtracting vigor. Total scores range from -24 to 96, with a higher score indicating more fatigue.</description>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.67" spread="19.09"/>
                    <measurement group_id="O2" value="3.25" spread="27.54"/>
                    <measurement group_id="O3" value="-9.67" spread="6.81"/>
                    <measurement group_id="O4" value="-9.25" spread="1.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Hemoglobin Level at Week 0</title>
        <description>Hemoglobin was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 11.6 - 15.0 g/dL.</description>
        <time_frame>week 0</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Hemoglobin Level at Week 0</title>
          <description>Hemoglobin was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 11.6 - 15.0 g/dL.</description>
          <units>g/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.42" spread="0.97"/>
                    <measurement group_id="O2" value="12.78" spread="0.71"/>
                    <measurement group_id="O3" value="12.4" spread="0.53"/>
                    <measurement group_id="O4" value="13.05" spread="0.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Hemoglobin Level Measured at Week 4</title>
        <description>Hemoglobin was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 11.6 - 15.0 g/dL.</description>
        <time_frame>week 4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Hemoglobin Level Measured at Week 4</title>
          <description>Hemoglobin was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 11.6 - 15.0 g/dL.</description>
          <units>g/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.05" spread="0.49"/>
                    <measurement group_id="O2" value="12.03" spread="0.43"/>
                    <measurement group_id="O3" value="12.6" spread="0.37"/>
                    <measurement group_id="O4" value="13.2" spread="0.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Hemoglobin Level Measured at Week 8</title>
        <description>Hemoglobin was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 11.6 - 15.0 g/dL.</description>
        <time_frame>week 8</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Hemoglobin Level Measured at Week 8</title>
          <description>Hemoglobin was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 11.6 - 15.0 g/dL.</description>
          <units>g/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.55" spread="0.35"/>
                    <measurement group_id="O2" value="11.97" spread="0.76"/>
                    <measurement group_id="O3" value="12.5" spread="0.08"/>
                    <measurement group_id="O4" value="12.95" spread="1.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Hematocrit Level Measured at Week 0</title>
        <description>Hematocrit was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 35.7 - 45.2%.</description>
        <time_frame>week 0</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Hematocrit Level Measured at Week 0</title>
          <description>Hematocrit was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 35.7 - 45.2%.</description>
          <units>percent of red blood cells</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.53" spread="2.16"/>
                    <measurement group_id="O2" value="38.55" spread="1.42"/>
                    <measurement group_id="O3" value="37.25" spread="2.07"/>
                    <measurement group_id="O4" value="31.88" spread="13.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Hematocrit Level Was Measured at 4 Weeks</title>
        <description>Hematocrit was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 35.7 - 45.2%.</description>
        <time_frame>4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Hematocrit Level Was Measured at 4 Weeks</title>
          <description>Hematocrit was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 35.7 - 45.2%.</description>
          <units>percent of red blood cells</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.08" spread="0.84"/>
                    <measurement group_id="O2" value="37.38" spread="0.82"/>
                    <measurement group_id="O3" value="38.13" spread="0.77"/>
                    <measurement group_id="O4" value="39.1" spread="1.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Hematocrit Level Measured at Week 8</title>
        <description>Hematocrit was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 35.7 - 45.2%.</description>
        <time_frame>week 8</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil, Then Placebo</title>
            <description>Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.</description>
          </group>
          <group group_id="O2">
            <title>Tadalfil, Then Placebo</title>
            <description>Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.</description>
          </group>
          <group group_id="O3">
            <title>Placebo, Then Sildenafil</title>
            <description>Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.</description>
          </group>
          <group group_id="O4">
            <title>Placebo, Then Tadalafil</title>
            <description>Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.</description>
          </group>
        </group_list>
        <measure>
          <title>Hematocrit Level Measured at Week 8</title>
          <description>Hematocrit was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 35.7 - 45.2%.</description>
          <units>percent of red blood cells</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.38" spread="0.44"/>
                    <measurement group_id="O2" value="36.6" spread="1.94"/>
                    <measurement group_id="O3" value="38.1" spread="1.19"/>
                    <measurement group_id="O4" value="38.4" spread="3.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Sildenafil</title>
          <description>Sildenafil (50mg/day) daily for 4 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Tadalfil</title>
          <description>Tadalafil (10mg/day) daily for 4 weeks.</description>
        </group>
        <group group_id="E3">
          <title>Placebo</title>
          <description>Placebo daily for week 4 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <description>Syncope following administration of Sildenafil 50mg.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Redness at site of muscle biopsy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Melinda Sheffield-Moore</name_or_title>
      <organization>University of Texas Medical Branch</organization>
      <phone>409-772-8707</phone>
      <email>melmoore@utmb.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01661595
org study id: 12-153
nct id: NCT01661595
lead sponsor: 
has dmc: Yes
This study is funded by the Moody Endowment. In this project, we will investigate the
      potential effect of skeletal muscle nitric oxide (NO) production on skeletal muscle
      anabolism, muscle strength, physical function, and body composition in older individuals.
      Further, we will determine whether augmentation of NO-mediated signaling reduces fatigue and
      fatigability.
The Investigators hypothesize that upregulation of skeletal muscle NO-cGMP mediated responses
      through phosphodiesterase (PDE) inhibition by sildenafil or tadalafil causes an acute
      anabolic response of skeletal muscle protein synthesis. NO is well-known to elicit
      vasodilation through stimulation of cGMP signaling, and NO-mediated changes in muscle
      perfusion may influence both skeletal muscle anabolism and perceptual fatigue. To measure
      skeletal muscle protein synthesis, we will infuse a stable isotope tracer of phenylalanine
      and measure its incorporation into skeletal muscle proteins following a dose of sildenafil,
      tadalafil, or placebo. The Investigators will also determine whether differences exist
      between men and women in response to PDE inhibition. As skeletal muscle NO-cGMP signaling has
      been implicated in fatigue responses, we will assess the acute effect of sildenafil and
      tadalafil on fatigue. Fatigue can be manifested both as a performance deficit at a local
      level (e.g., a reduced ability of skeletal muscle to produce power or force) as well as a
      subjective experience of lacking physical or mental energy. Accordingly, we will use more
      than one means (skeletal muscle performance, fatigue questionnaires, accelerometers) to study
      fatigue. The Investigators hypothesize that sildenafil or tadalafil will acutely reduce
      exercise-associated fatigability and skeletal muscle fatigue development
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Subjects were assigned to one of 4 arms:
Sildenafil (50mg/day) for weeks 0-4. Placebo for weeks 5-8.
Tadalafil (10mg/day) for weeks 0-4. Placebo for weeks 5-8.
Placebo for weeks 0-4. Sildenafil (50mg/day) for weeks 5-8.
Placebo for weeks 0-4. Tadalafil (10mg/day) for weeks 5-8.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Skeletal Muscle Fatigue as Measured by Biodex 4 Pro After 4 Weeks of Placebo
time frame: after 4 weeks of placebo
description: Isokinetic Fatigue Measure (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 50 contractions were performed at 100% force, one contraction every second. Isokinetic fatigue will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug. Data is presented as mean maximum force over all 50 kicks.
measure: Skeletal Muscle Fatigue as Measured by Biodex 4 Pro After 4 Weeks of Active Drug
time frame: after 4 weeks of active drug
description: Isokinetic Fatigue Measure (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 50 contractions were performed at 100% force, one contraction every second. Isokinetic fatigue will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug. Data is presented as mean maximum force over all 50 kicks.
measure: Exercised Induced Fatigability as Measured by Fatigue Rating Scale After 4 Weeks of Placebo
time frame: after 4 weeks of placebo
description: The fatigue rating scale is a scale from 0 to 10 with 0 being no fatigue at all and 10 being the worst fatigue the subject can imagine. The subject is asked to rate their level of fatigue in their leg. This test was performed before and immedicately after the Biodex leg fatigue test after 4 weeks of placebo. Data is presented as change in scale from pre fatigue test to post fatigue test, with a higher score indicating a greater level of fatigue.
measure: Exercised Induced Fatigability as Measured by Fatigue Rating Scale After 4 Weeks of Active Drug
time frame: after 4 weeks of active drug
description: The fatigue rating scale is a scale from 0 to 10 with 0 being no fatigue at all and 10 being the worst fatigue the subject can imagine. The subject is asked to rate their level of fatigue in their leg. This test was performed before and immedicately after the Biodex leg fatigue test. Data is presented as change in scale from pre fatigue test to post fatigue test, with a higher score indicating a greater level of fatigue.
measure: Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Placebo
time frame: after 4 weeks of placebo
description: Peak isometric strength is measured on a Biodex System 4 Pro. This test is isolated to the quadricep muscle of one leg. Isometric test is performed at 90 degrees with 5 seconds of force production for each contraction and 15 seconds of rest. 1 set of 3 contractions at 100% force performed. Isometric strength was measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.
measure: Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Active Drug.
time frame: after 4 weeks of active drug
description: Peak isometric strength is measured on a Biodex System 4 Pro. This test is isolated to the quadricep muscle of one leg. Isometric test is performed at 90 degrees with 5 seconds of force production for each contraction and 15 seconds of rest. 1 set of 3 contractions at 100% force performed. Isometric strength was measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.
measure: Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Placebo.
time frame: after 4 weeks of placebo
description: Isokinetic strength (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 1 set of 3 contractions were performed at 100% force. Isokinetic strength will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.
measure: Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Active Drug
time frame: after 4 weeks of active drug
description: Isokinetic strength (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 1 set of 3 contractions were performed at 100% force. Isokinetic strength will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.
measure: Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 0.
time frame: week 0
description: Lean Body Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.
measure: Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 4.
time frame: week 4
description: Lean Body Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.
measure: Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 8.
time frame: week 8
description: Lean Body Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.
measure: Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 0.
time frame: week 0
description: Fat Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.
measure: Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 4.
time frame: week 4
description: Fat Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.
measure: Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 8.
time frame: week 8
description: Fat Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.
measure: Walking Distance at 100% Effort as Measured by Walking Test After 4 Weeks of Placebo
time frame: after 4 weeks of placebo
description: Walking performance will be assessed during 2 minutes of walking in long corridor hallways. Subjects will be asked to walk at 100% effort (as quickly as they can safely walk without running) for 2 minutes. Distance traveled for the 2 minutes will be recorded. The walking test will be completed at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.
measure: Walking Distance at 100% Effort as Measured by Walking Test After 4 Weeks of Active Drug
time frame: after 4 weeks of active drug
description: Walking performance will be assessed during 2 minutes of walking in long corridor hallways. Subjects will be asked to walk at 100% effort (as quickly as they can safely walk without running) for 2 minutes. Distance traveled for the 2 minutes will be recorded. The walking test will be completed at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug.
measure: Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 0
time frame: Week 0
description: Fatigue symptoms will be measured using the 30-item Multidimensional Fatigue Symptom Inventory - Short Form, a validated measure that yields one overall score of total fatigue calculated using five sub scales (general, physical, emotional, mental, vigor). With the exception of the vigor sub scale, higher scores indicate greater fatigue. Total fatigue score is calculated by summing the sub categories (general, physical, emotional and mental) and subtracting vigor. Total scores range from -24 to 96, with a higher score indicating more fatigue.
measure: Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 4
time frame: week 4
description: Fatigue symptoms will be measured using the 30-item Multidimensional Fatigue Symptom Inventory - Short Form, a validated measure that yields one overall score of total fatigue calculated using five sub scales (general, physical, emotional, mental, vigor). With the exception of the vigor sub scale, higher scores indicate greater fatigue. Total fatigue score is calculated by summing the sub categories (general, physical, emotional and mental) and subtracting vigor. Total scores range from -24 to 96, with a higher score indicating more fatigue.
measure: Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 8
time frame: week 8
description: Fatigue symptoms will be measured using the 30-item Multidimensional Fatigue Symptom Inventory - Short Form, a validated measure that yields one overall score of total fatigue calculated using five sub scales (general, physical, emotional, mental, vigor). With the exception of the vigor sub scale, higher scores indicate greater fatigue. Total fatigue score is calculated by summing the sub categories (general, physical, emotional and mental) and subtracting vigor. Total scores range from -24 to 96, with a higher score indicating more fatigue.
measure: Hemoglobin Level at Week 0
time frame: week 0
description: Hemoglobin was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 11.6 - 15.0 g/dL.
measure: Hemoglobin Level Measured at Week 4
time frame: week 4
description: Hemoglobin was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 11.6 - 15.0 g/dL.
measure: Hemoglobin Level Measured at Week 8
time frame: week 8
description: Hemoglobin was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 11.6 - 15.0 g/dL.
measure: Hematocrit Level Measured at Week 0
time frame: week 0
description: Hematocrit was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 35.7 - 45.2%.
measure: Hematocrit Level Was Measured at 4 Weeks
time frame: 4 weeks
description: Hematocrit was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 35.7 - 45.2%.
measure: Hematocrit Level Measured at Week 8
time frame: week 8
description: Hematocrit was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 35.7 - 45.2%.
arm group label: Sildenafil / Placebo
arm group type: Active Comparator
description: 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 0-4. Placebo for weeks 5-8.
arm group label: Tadalafil / Placebo
arm group type: Active Comparator
description: 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 0-4. Placebo for weeks 5-8.
arm group label: Placebo / Sildenafil
arm group type: Active Comparator
description: Placebo for weeks 0-4. 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 5-8.
arm group label: Placebo / Tadalafil
arm group type: Active Comparator
description: Placebo for weeks 0-4. 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 5-8.
intervention type: Drug
intervention name: Sildenafil
description: 50 mg/day for 4 weeks
arm group label: Placebo / Sildenafil
arm group label: Sildenafil / Placebo
other name: Viagra
other name: Revatio
intervention type: Drug
intervention name: tadalafil
description: 10 mg/day for 4 weeks.
arm group label: Placebo / Tadalafil
arm group label: Tadalafil / Placebo
other name: Cialis
other name: Adcirca
intervention type: Drug
intervention name: Placebo
description: Placebo 1 capsule per day for four weeks.
arm group label: Placebo / Sildenafil
arm group label: Placebo / Tadalafil
arm group label: Sildenafil / Placebo
arm group label: Tadalafil / Placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Melinda Sheffield-Moore, PhD
role: Principal Investigator
affiliation: University of Texas Medical Branch, Galveston
facility: 
country: United States
responsible party type: Sponsor
mesh term: Fatigue
mesh term: Sildenafil Citrate
mesh term: Tadalafil
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 