<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/NCT02248701</url>
  </required_header>
  <id_info>
    <org_study_id>B1449-R</org_study_id>
    <secondary_id>1I01RX001449-01A1</secondary_id>
    <nct_id>NCT02248701</nct_id>
  </id_info>
  <brief_title>Testosterone Plus Finasteride Treatment After Spinal Cord Injury</brief_title>
  <official_title>Higher-Than-Replacement Testosterone Plus Finasteride Treatment After SCI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether testosterone plus finasteride treatment&#xD;
      will improve musculoskeletal health, neuromuscular function, body composition, and metabolic&#xD;
      health in hypogonadal men who have experienced ambulatory dysfunction subsequent to&#xD;
      incomplete spinal cord injury. The investigators hypothesize that this treatment will improve&#xD;
      bone mineral density, enhance muscle size and muscle function, and improve body composition,&#xD;
      without causing prostate enlargement.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Men with spinal cord injury (SCI) experience a high prevalence of hypogonadism which&#xD;
      influences the neural, muscular, skeletal, and body composition deficits that occur after&#xD;
      injury. It remains unknown whether testosterone administration improves bone mineral density,&#xD;
      muscle mass and muscle function, and body composition / metabolic health in hypogonadal men&#xD;
      who have experienced ambulatory dysfunction subsequent to incomplete spinal cord injury. In&#xD;
      addition, it is unknown whether testosterone or the 5-alpha reduced metabolite&#xD;
      dihydrotestosterone (an endogenous metabolite of testosterone) mediate effects in these and&#xD;
      other tissues.&#xD;
&#xD;
      For this study hypogonadal men with motor incomplete spinal cord injury who present with&#xD;
      ambulatory dysfunction will be randomized to receive testosterone plus the 5-alpha reductase&#xD;
      inhibitor finasteride or a placebo treatment for 12 months. Testosterone or placebo injection&#xD;
      will be administered weekly; finasteride or placebo will be administered daily. Participants&#xD;
      will be assessed at study entry and at 1-6 month intervals thereafter. Assessments will&#xD;
      include measurements such as a dual energy x-ray absorptiometry (DEXA) scan, MRI scan, and&#xD;
      muscle performance tests. Participants will also have several safety tests, including&#xD;
      electrocardiogram (EKG) for cardiac electrophysiology, prostate digital rectal exam and&#xD;
      prostate ultrasound sizing for prostate health, and blood tests to assess hematocrit, liver&#xD;
      enzymes (AST and ALT), prostate specific antigen (PSA), cholesterol, and other health&#xD;
      markers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Enrollment difficulties&#xD;
  </why_stopped>
  <start_date type="Actual">January 16, 2017</start_date>
  <completion_date type="Actual">August 13, 2021</completion_date>
  <primary_completion_date type="Actual">August 13, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Hip Bone Mineral Density</measure>
    <time_frame>Baseline, 6 months, 12 months</time_frame>
    <description>Change in hip bone mineral density assessed via dual-energy X-ray absorptiometry (DXA)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in Muscle Cross-Sectional Area</measure>
    <time_frame>Baseline, 6 months, 12 months</time_frame>
    <description>Change in thigh muscle cross-sectional area assessed via MRI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Total Body Fat</measure>
    <time_frame>Baseline, 6 months, 12 months</time_frame>
    <description>Change in total body fat assessed via DXA</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Walking Speed</measure>
    <time_frame>Baseline, 6 months, 12 months</time_frame>
    <description>Change in 10 m walking speed</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Neuromuscular Function</measure>
    <time_frame>Baseline, 6 months, 12 months</time_frame>
    <description>Change in thigh muscle force production assessed via dynamometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Visceral Fat</measure>
    <time_frame>Baseline, 6 months, 12 months</time_frame>
    <description>Change in visceral fat mass assessed via DXA</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Spinal Cord Injury</condition>
  <condition>Spinal Cord Injuries</condition>
  <condition>Trauma, Nervous System</condition>
  <condition>Wounds and Injuries</condition>
  <condition>Central Nervous System Diseases</condition>
  <condition>Nervous System Diseases</condition>
  <condition>Spinal Cord Diseases</condition>
  <condition>Gonadal Disorders</condition>
  <condition>Endocrine System Diseases</condition>
  <condition>Hypogonadism</condition>
  <condition>Genital Diseases, Male</condition>
  <arm_group>
    <arm_group_label>testosterone enanthate, finasteride</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Testosterone enanthate via i.m. injection (125 mg/week) and finasteride orally (5 mg/day)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo treatment</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo via i.m. injection (once weekly) and placebo pill orally (daily)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Testosterone Enanthate</intervention_name>
    <description>Subjects receive testosterone (125 mg/week) by intramuscular injection</description>
    <arm_group_label>testosterone enanthate, finasteride</arm_group_label>
    <other_name>delatestryl</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Finasteride</intervention_name>
    <description>Subjects receive finasteride (5 mg/day) orally</description>
    <arm_group_label>testosterone enanthate, finasteride</arm_group_label>
    <other_name>proscar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo injection</intervention_name>
    <description>Subjects receive placebo (weekly) by intramuscular injection</description>
    <arm_group_label>placebo treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo pill</intervention_name>
    <description>Subjects receive placebo pill (daily) orally</description>
    <arm_group_label>placebo treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male &gt; 18 years of age&#xD;
&#xD;
          -  Traumatic, vascular, or orthopedic spinal cord injury between C2-L3 &gt;12 months prior&#xD;
             to enrollment&#xD;
&#xD;
          -  Motor incomplete spinal cord (AIS C/D)&#xD;
&#xD;
          -  Ambulatory dysfunction&#xD;
&#xD;
          -  Medically stable condition that is asymptomatic for bladder infection, decubiti,&#xD;
             cardiopulmonary disease, or other significant medical conditions&#xD;
&#xD;
          -  Serum total testosterone (&lt;325 ng/dL) or bioavailable testosterone (&lt;70 ng/dL)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Currently participating in another research protocol that may influence study outcomes&#xD;
&#xD;
          -  Life expectancy &lt;1 year&#xD;
&#xD;
          -  History of or current congenital spinal cord injury or other degenerative spinal&#xD;
             disorder&#xD;
&#xD;
          -  Diagnosis of multiple sclerosis, amyotrophic lateral sclerosis, or other neurologic&#xD;
             impairment/injury&#xD;
&#xD;
          -  History of venous thromboembolism within the last 6 months, specifically deep venous&#xD;
             thromboembolism and pulmonary embolism, history of recurrent venous thromboembolism or&#xD;
             know hereditary thrombophilia&#xD;
&#xD;
          -  Poorly compensated or uncontrolled cardiovascular disease&#xD;
&#xD;
          -  Any major cardiovascular event within the last 12 months (defined as a history of&#xD;
             acute myocardial infarction, any cardiac revascularization procedure including&#xD;
             angioplasty, stenting, or coronary artery bypass grafting, hospitalization due to&#xD;
             unstable angina, transient ischemic attack, or stroke)&#xD;
&#xD;
          -  Any angina that is not controlled on a current medical regimen (Canadian class II,&#xD;
             III, or IV)&#xD;
&#xD;
          -  New York Heart Association (NYHA) class III or IV congestive heart failure&#xD;
&#xD;
          -  Systolic blood pressure &gt;160 mmHg or diastolic blood pressure &gt;100 mm Hg&#xD;
&#xD;
          -  Poorly controlled arrhythmia&#xD;
&#xD;
          -  Severe valvular disease&#xD;
&#xD;
          -  LDL cholesterol &gt;160 mg/dl with known history of any major cardiovascular event, as&#xD;
             defined above, within the last 12 months&#xD;
&#xD;
          -  Baseline EKG findings (e.g. left bundle branch block) or marked EKG abnormalities that&#xD;
             would preclude serial screening for occult ischemic events&#xD;
&#xD;
          -  Current prostate, breast, or other organ cancer&#xD;
&#xD;
          -  History of prostate, breast, or other organ cancer, with the exceptions of completely&#xD;
             resolved basal or squamous cell carcinoma for a duration of &gt;24 months or completely&#xD;
             resolved melanoma for a duration of &gt;24 months&#xD;
&#xD;
          -  Serum prostate-specific antigen (PSA) &gt;3.0 ng/ml&#xD;
&#xD;
          -  History of benign prostate enlargement (BPE) &gt;40cc, evaluated via TRUS&#xD;
&#xD;
          -  Hematocrit &gt;47%&#xD;
&#xD;
          -  Liver enzymes (AST / ALT) above normal upper limit&#xD;
&#xD;
          -  Creatinine &gt;1.4 mg/dL&#xD;
&#xD;
          -  Serum calcium &gt;10.5 mg/dL&#xD;
&#xD;
          -  Gynecomastia&#xD;
&#xD;
          -  Mental state that precludes understanding of the protocol&#xD;
&#xD;
          -  Diagnosed, but untreated moderate or severe sleep apnea&#xD;
&#xD;
          -  Spinal nutrition screening tool score &gt;15&#xD;
&#xD;
          -  Severe claustrophobia that precludes MRI testing&#xD;
&#xD;
          -  Current anticoagulant therapy&#xD;
&#xD;
          -  Use of any of the following pharmacologic agents in the previous 3 months&#xD;
             (testosterone, leuprolide, androgenic hormones, growth hormone, oral androgen&#xD;
             precursors, 5-alpha reductase or aromatase inhibitors)&#xD;
&#xD;
          -  Use of anti-resorptive or bone anabolic drug therapy in the previous 6 months&#xD;
&#xD;
          -  Known allergy to sesame oil&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Participants must be male</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joshua F Yarrow, PhD MS BS</last_name>
    <role>Principal Investigator</role>
    <affiliation>North Florida/South Georgia Veterans Health System, Gainesville, FL</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>James A. Haley Veterans' Hospital, Tampa, FL</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Florida/South Georgia Veterans Health System, Gainesville, FL</name>
      <address>
        <city>Gainesville</city>
        <state>Georgia</state>
        <zip>32608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>September 22, 2014</study_first_submitted>
  <study_first_submitted_qc>September 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <disposition_first_submitted>July 20, 2022</disposition_first_submitted>
  <disposition_first_submitted_qc>July 20, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">July 28, 2022</disposition_first_posted>
  <last_update_submitted>July 28, 2022</last_update_submitted>
  <last_update_submitted_qc>July 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Testosterone</keyword>
  <keyword>Testosterone enanthate</keyword>
  <keyword>Testosterone undecanoate</keyword>
  <keyword>Testosterone 17 beta-cypionate</keyword>
  <keyword>Methyltestosterone</keyword>
  <keyword>Androgens</keyword>
  <keyword>Hormones</keyword>
  <keyword>Hormone Substitutes, and Hormone Antagonists</keyword>
  <keyword>Physiologic Effects of Drugs</keyword>
  <keyword>Pharmacologic Actions</keyword>
  <keyword>Antineoplastic Agents, Hormonal</keyword>
  <keyword>Antineoplastic Agents</keyword>
  <keyword>Therapeutic Uses</keyword>
  <keyword>Anabolic Agents</keyword>
  <keyword>Testosterone Replacement Therapy</keyword>
  <keyword>Dual Energy X ray Absorptiometry</keyword>
  <keyword>Lean Tissue Mass</keyword>
  <keyword>Body Composition</keyword>
  <keyword>Lipid and Glucose profile</keyword>
  <keyword>Muscle Strength</keyword>
  <keyword>5-alpha Reductase</keyword>
  <keyword>Muscle Mass</keyword>
  <keyword>Bone Mineral Density</keyword>
  <keyword>Adipose Tissue</keyword>
  <keyword>Body Fat</keyword>
  <keyword>Density, Bone</keyword>
  <keyword>Bone Formation</keyword>
  <keyword>Bone Resorption</keyword>
  <keyword>Bone Density Conservation Agents</keyword>
  <keyword>Magnetic Resonance Imaging</keyword>
  <keyword>Muscle, Skeletal</keyword>
  <keyword>Bone and Bones</keyword>
  <keyword>Gait</keyword>
  <keyword>Walking</keyword>
  <keyword>Locomotion</keyword>
  <keyword>Motor Activity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Cord Injuries</mesh_term>
    <mesh_term>Nervous System Diseases</mesh_term>
    <mesh_term>Central Nervous System Diseases</mesh_term>
    <mesh_term>Spinal Cord Diseases</mesh_term>
    <mesh_term>Trauma, Nervous System</mesh_term>
    <mesh_term>Genital Diseases</mesh_term>
    <mesh_term>Genital Diseases, Male</mesh_term>
    <mesh_term>Hypogonadism</mesh_term>
    <mesh_term>Endocrine System Diseases</mesh_term>
    <mesh_term>Gonadal Disorders</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methyltestosterone</mesh_term>
    <mesh_term>Finasteride</mesh_term>
    <mesh_term>Testosterone</mesh_term>
    <mesh_term>Testosterone undecanoate</mesh_term>
    <mesh_term>Testosterone enanthate</mesh_term>
    <mesh_term>Testosterone 17 beta-cypionate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data will be shared according to the requirements described by the Department of Veterans Affairs, Office of Research &amp; Development.</ipd_description>
    <ipd_time_frame>Data will be shared according to the requirements described by the Department of Veterans Affairs, Office of Research &amp; Development.</ipd_time_frame>
    <ipd_access_criteria>Data will be shared according to the requirements described by the Department of Veterans Affairs, Office of Research &amp; Development.</ipd_access_criteria>
  </patient_data>
  <pending_results>
    <submitted>August 29, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT02248701
org study id: B1449-R
secondary id: 1I01RX001449-01A1
nct id: NCT02248701
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to determine whether testosterone plus finasteride treatment
      will improve musculoskeletal health, neuromuscular function, body composition, and metabolic
      health in hypogonadal men who have experienced ambulatory dysfunction subsequent to
      incomplete spinal cord injury. The investigators hypothesize that this treatment will improve
      bone mineral density, enhance muscle size and muscle function, and improve body composition,
      without causing prostate enlargement.
Men with spinal cord injury (SCI) experience a high prevalence of hypogonadism which
      influences the neural, muscular, skeletal, and body composition deficits that occur after
      injury. It remains unknown whether testosterone administration improves bone mineral density,
      muscle mass and muscle function, and body composition / metabolic health in hypogonadal men
      who have experienced ambulatory dysfunction subsequent to incomplete spinal cord injury. In
      addition, it is unknown whether testosterone or the 5-alpha reduced metabolite
      dihydrotestosterone (an endogenous metabolite of testosterone) mediate effects in these and
      other tissues.

      For this study hypogonadal men with motor incomplete spinal cord injury who present with
      ambulatory dysfunction will be randomized to receive testosterone plus the 5-alpha reductase
      inhibitor finasteride or a placebo treatment for 12 months. Testosterone or placebo injection
      will be administered weekly; finasteride or placebo will be administered daily. Participants
      will be assessed at study entry and at 1-6 month intervals thereafter. Assessments will
      include measurements such as a dual energy x-ray absorptiometry (DEXA) scan, MRI scan, and
      muscle performance tests. Participants will also have several safety tests, including
      electrocardiogram (EKG) for cardiac electrophysiology, prostate digital rectal exam and
      prostate ultrasound sizing for prostate health, and blood tests to assess hematocrit, liver
      enzymes (AST and ALT), prostate specific antigen (PSA), cholesterol, and other health
      markers.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Hip Bone Mineral Density
time frame: Baseline, 6 months, 12 months
description: Change in hip bone mineral density assessed via dual-energy X-ray absorptiometry (DXA)
measure: Changes in Muscle Cross-Sectional Area
time frame: Baseline, 6 months, 12 months
description: Change in thigh muscle cross-sectional area assessed via MRI
measure: Change in Total Body Fat
time frame: Baseline, 6 months, 12 months
description: Change in total body fat assessed via DXA
measure: Change in Walking Speed
time frame: Baseline, 6 months, 12 months
description: Change in 10 m walking speed
measure: Change in Neuromuscular Function
time frame: Baseline, 6 months, 12 months
description: Change in thigh muscle force production assessed via dynamometry
measure: Change in Visceral Fat
time frame: Baseline, 6 months, 12 months
description: Change in visceral fat mass assessed via DXA
arm group label: testosterone enanthate, finasteride
arm group type: Experimental
description: Testosterone enanthate via i.m. injection (125 mg/week) and finasteride orally (5 mg/day)
arm group label: placebo treatment
arm group type: Placebo Comparator
description: Placebo via i.m. injection (once weekly) and placebo pill orally (daily)
intervention type: Drug
intervention name: Testosterone Enanthate
description: Subjects receive testosterone (125 mg/week) by intramuscular injection
arm group label: testosterone enanthate, finasteride
other name: delatestryl
intervention type: Drug
intervention name: Finasteride
description: Subjects receive finasteride (5 mg/day) orally
arm group label: testosterone enanthate, finasteride
other name: proscar
intervention type: Drug
intervention name: Placebo injection
description: Subjects receive placebo (weekly) by intramuscular injection
arm group label: placebo treatment
intervention type: Drug
intervention name: Placebo pill
description: Subjects receive placebo pill (daily) orally
arm group label: placebo treatment
criteria: 
gender: Male
gender based: Yes
gender description: Participants must be male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Joshua F Yarrow, PhD MS BS
role: Principal Investigator
affiliation: North Florida/South Georgia Veterans Health System, Gainesville, FL
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Spinal Cord Injuries
mesh term: Nervous System Diseases
mesh term: Central Nervous System Diseases
mesh term: Spinal Cord Diseases
mesh term: Trauma, Nervous System
mesh term: Genital Diseases
mesh term: Genital Diseases, Male
mesh term: Hypogonadism
mesh term: Endocrine System Diseases
mesh term: Gonadal Disorders
mesh term: Wounds and Injuries
mesh term: Methyltestosterone
mesh term: Finasteride
mesh term: Testosterone
mesh term: Testosterone undecanoate
mesh term: Testosterone enanthate
mesh term: Testosterone 17 beta-cypionate
sharing ipd: Yes
ipd description: Data will be shared according to the requirements described by the Department of Veterans Affairs, Office of Research & Development.
ipd time frame: Data will be shared according to the requirements described by the Department of Veterans Affairs, Office of Research & Development.
ipd access criteria: Data will be shared according to the requirements described by the Department of Veterans Affairs, Office of Research & Development.
submitted: August 29, 2023