<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/NCT04405180</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY20110334</org_study_id>
    <secondary_id>R01AG058883</secondary_id>
    <nct_id>NCT04405180</nct_id>
  </id_info>
  <brief_title>Nitrites, Skeletal Muscle Mitochondrial Bioenergetics, and Physical Activity in Old Age</brief_title>
  <acronym>Nitrite</acronym>
  <official_title>Nitrites, Skeletal Muscle Mitochondrial Bioenergetics, and Physical Activity in Old Age</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gladwin, Mark, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute on Aging (NIA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</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>
      This 2-site randomized double blinded controlled trial is to confirm and more definitively&#xD;
      clarify the impact of a 12-week course of nitrite versus placebo on mitochondrial&#xD;
      bioenergetics in older sedentary adults. This investigator will take an integrative&#xD;
      physiology approach to determine the effect of nitrite therapy on a comprehensive assessment&#xD;
      of mitochondrial energetics, skeletal muscle vascular function, and whole body physical&#xD;
      function (cardiorespiratory function, exercise endurance, strength, balance, and physical&#xD;
      activity) and fatigability.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Old age is associated with declining skeletal muscle mitochondrial bioenergetics with related&#xD;
      decrements in cardiorespiratory fitness (CRF) and physical function that predispose to&#xD;
      frailty, disability, and diminished quality of life. While exercise training may moderate and&#xD;
      possibly even reverse declines in mitochondrial bioenergetics, potential for such benefit is&#xD;
      typically confounded by exercise intolerance with early fatigability that results from the&#xD;
      same age-related mitochondrial declines. Consequently, sedentariness is endemic and insidious&#xD;
      among the growing population of older adults. This trial is to study the utility of inorganic&#xD;
      nitrite salts as a novel means to modify this detrimental pattern. Classic studies&#xD;
      demonstrate that nitrite facilitates hypoxic vasodilation in muscle. This investigator's&#xD;
      preliminary data suggests that nitrite treatment also augments skeletal muscle mitochondrial&#xD;
      bioenergetics in older adults. This investigator proposes improving mitochondrial function&#xD;
      will also be reflected in clinical parameters, including CRF as well as broader functional&#xD;
      attributes (endurance, strength, and balance) that enable physical activity (PA) and&#xD;
      opportunity to mitigate frailty and disability. As such, this application is in line with the&#xD;
      National Institute on Aging's mission to develop targeted interventions to prevent and treat&#xD;
      age-associated conditions. This multi-disciplinary team has published seminal work indicating&#xD;
      that mitochondrial bioenergetics and CRF are significant determinants of physical function in&#xD;
      older adults. In parallel efforts, this investigative team showed efficacy of chronic nitrite&#xD;
      therapy to improve mitochondrial bioenergetics in older sedentary adults. Only one month of&#xD;
      nitrite therapy significantly improved ex vivo assessments of mitochondrial energetics in&#xD;
      skeletal muscle biopsies, concomitant with increased skeletal muscle sirtuin-3 expression, a&#xD;
      nicotinamide adenine dinucleotide (NAD) dependent lysine deacetylase and key regulator of&#xD;
      mitochondrial metabolism. These key data reinforce the premise that nitrite enhances vital&#xD;
      mitochondrial metabolism in older adults. Moreover, improvement in muscle energetics in&#xD;
      nitrite-treated older adults was linked with increased exercise efficiency as evidenced by&#xD;
      reduced oxygen consumption (VO2) during submaximal steady-state walking. This data supports&#xD;
      the hypothesis that nitrite will make physical function easier such that physical activity&#xD;
      will increase.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 23, 2021</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</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>
    <intervention_model_description>Parallel assignment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Quadruple: Participant, Care Provider, Investigator, Outcome Assessor</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Skeletal muscle mitochondrial respiration State 3, Baseline to 12-week change</measure>
    <time_frame>12-week course of study drug supplementation, up to 16 weeks total</time_frame>
    <description>We will use high resolution respirometry via Oroboros Oxygraph 2k to assess the effects of 12 weeks of inorganic nitrite vs placebo on skeletal muscle mitochondrial respiration from samples obtained via vastus lateralis muscle biopsy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Skeletal Muscle adenosine triphosphate (ATP) production, Baseline to 12-week change</measure>
    <time_frame>12-week course of study drug supplementation, up to 16 weeks total</time_frame>
    <description>Using phosphorus-magnetic resonance spectroscopy, we will measure ATP production and how it will change after 12 weeks (up to 16 weeks) of inorganic nitrite supplementation vs placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cross-sectional area for each fiber type by skeletal muscle microscopy, Baseline to 12-week change</measure>
    <time_frame>12-week course of study drug supplementation, up to 16 weeks total</time_frame>
    <description>Using microscopy and immmunofluorescence, we will measure the cross-sectional area for each fiber type, relative fiber type number, and relative area composition of each muscle fiber type and mitochondrial content (area/section) after 12 weeks of inorganic nitrite supplementation vs placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in relative fiber type number by skeletal muscle microscopy, Baseline to 12-week change</measure>
    <time_frame>12-week course of study drug supplementation, up to 16 weeks total</time_frame>
    <description>Using microscopy and immmunofluorescence, we will measure the cross-sectional area for each fiber type, relative fiber type number, and relative area composition of each muscle fiber type and mitochondrial content (area/section) after 12 weeks of inorganic nitrite supplementation vs placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in relative area composition of each muscle fiber type by skeletal muscle microscopy, Baseline to 12-week change</measure>
    <time_frame>12-week course of study drug supplementation, up to 16 weeks total</time_frame>
    <description>Using microscopy and immmunofluorescence, we will measure the cross-sectional area for each fiber type, relative fiber type number, and relative area composition of each muscle fiber type and mitochondrial content (area/section) after 12 weeks of inorganic nitrite supplementation vs placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in mitochondrial content (area/section) by skeletal muscle microscopy, Baseline to 12-week change</measure>
    <time_frame>12-week course of study drug supplementation, up to 16 weeks total</time_frame>
    <description>Using microscopy and immmunofluorescence, we will measure the cross-sectional area for each fiber type, relative fiber type number, and relative area composition of each muscle fiber type and mitochondrial content (area/section) after 12 weeks of inorganic nitrite supplementation vs placebo.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Baseline to 12-week change in Peak oxygen uptake (VO2) achieved during progressive resistance exercise testing</measure>
    <time_frame>12-week course of study drug supplementation, up to 16 weeks total</time_frame>
    <description>We will measure changes in cardiorespiratory fitness including Peak oxygen uptake (VO2) achieved during progressive resistance exercise testing (Increased VO2 notes increased oxygen uptake).&#xD;
These will be assessed before and after 12 weeks (16 weeks total) of oral inorganic nitrite supplementation vs placebo.</description>
  </other_outcome>
  <other_outcome>
    <measure>Baseline to 12-week change in VO2 during steady state exercise</measure>
    <time_frame>12-week course of study drug supplementation, up to 16 weeks total</time_frame>
    <description>We will measure changes in cardiorespiratory fitness including VO2 during steady state exercise (Increased VO2 notes increased oxygen uptake).&#xD;
These will be assessed before and after 12 weeks (16 weeks total) of oral inorganic nitrite supplementation vs placebo.</description>
  </other_outcome>
  <other_outcome>
    <measure>Baseline to 12-week change in duration of constant work rate exercise</measure>
    <time_frame>12-week course of study drug supplementation, up to 16 weeks total</time_frame>
    <description>We will measure changes in cardiorespiratory fitness including duration of constant work rate exercise (longer times denote increased exercise capacity).&#xD;
These will be assessed before and after 12 weeks (16 weeks total) of oral inorganic nitrite supplementation vs placebo.</description>
  </other_outcome>
  <other_outcome>
    <measure>Baseline to 12-week change in time of 400 m corridor walking</measure>
    <time_frame>12-week course of study drug supplementation, up to 16 weeks total</time_frame>
    <description>We will measure changes in cardiorespiratory fitness including time of 400 m corridor walking (decreased time denote increased exercise capacity).&#xD;
These will be assessed before and after 12 weeks (16 weeks total) of oral inorganic nitrite supplementation vs placebo.</description>
  </other_outcome>
  <other_outcome>
    <measure>Baseline to 12-week change in fatiguability during Steady State walking</measure>
    <time_frame>12-week course of study drug supplementation, up to 16 weeks total</time_frame>
    <description>Using the Borg Rating of Perceived Exertion (units 6-20), we will measure how much fatiguing the steady-state walking test (at 1.5 mph) is to the participant. We will compare this to the RPE of this test again after 12-weeks (up to 16-weeks) of inorganic nitrite supplementation vs placebo. Lower RPE notes improvement.</description>
  </other_outcome>
  <other_outcome>
    <measure>Short Physical Performance Battery, Baseline to 12-week change</measure>
    <time_frame>12-week course of study drug supplementation, up to 16 weeks total</time_frame>
    <description>Will assess SPPB Score and its change after 12-weeks (up to 16-weeks) of inorganic nitrite supplementation vs placebo. Higher score shows improvement.</description>
  </other_outcome>
  <other_outcome>
    <measure>Handgrip Strength, Baseline to 12-week change</measure>
    <time_frame>12-week course of study drug supplementation, up to 16 weeks total</time_frame>
    <description>Will assess handgrip strength in the dominant hand, and its change after 12-weeks (up to 16-weeks) of inorganic nitrite supplementation vs placebo. Higher score shows improvement.</description>
  </other_outcome>
  <other_outcome>
    <measure>Steps - Physical activity (accelerometry)</measure>
    <time_frame>12-week course of study drug supplementation, up to 16 weeks total</time_frame>
    <description>Using an Actigraph accelerometry device on the participant's wrist, will assess daily steps and its change with 12-weeks (up to 16-weeks) of inorganic nitrite supplementation vs placebo. Higher number of steps note improvement.</description>
  </other_outcome>
  <other_outcome>
    <measure>Vector Magnitude Counts - Physical activity (accelerometry)</measure>
    <time_frame>12-week course of study drug supplementation, up to 16 weeks total</time_frame>
    <description>Using an Actigraph accelerometry device on the participant's wrist, will assess daily vector magnitude counts and its change with 12-weeks (up to 16-weeks) of inorganic nitrite supplementation vs placebo. Higher number of counts note improvement.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Aging</condition>
  <condition>Sedentary Lifestyle</condition>
  <condition>Frailty</condition>
  <arm_group>
    <arm_group_label>20 mg Sodium Nitrite TID Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject is to receive active study drug three times per day during treatment (12 weeks +/- 5 days) period and then after the treatment period (up to 16 weeks total).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Control Arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subject is to receive placebo three times per day during treatment period (12 weeks +/- 5 days) and then after the treatment testing period (up to 16 weeks total).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>Oral placebo capsule at a dose of 20 mg administered three times per day, during the day.</description>
    <arm_group_label>Placebo Control Arm</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>20mg sodium nitrite tid</intervention_name>
    <description>Oral, inorganic sodium nitrite capsule at a dose of 20 mg administered three times per day, during the day.</description>
    <arm_group_label>20 mg Sodium Nitrite TID Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥70 years&#xD;
&#xD;
          -  Sedentary (&lt;1 hour/week of volitional exercise activity)&#xD;
&#xD;
          -  Clinically stable (euvolemic; baseline HR &lt;100 bpm) and without hospitalization or&#xD;
             invasive cardiac procedure for 6 weeks&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Blood pressure &lt;110 or &gt;160/95 mmHg&#xD;
&#xD;
          -  Orthopedic or other chronic condition which limits physical activity or exercise&#xD;
             testing assessments&#xD;
&#xD;
          -  If valve replacement has been performed, patient may not be enrolled for 12 months&#xD;
             after this procedure&#xD;
&#xD;
          -  Severe peripheral or pulmonary artery disease&#xD;
&#xD;
          -  Anemia: Hgb &lt;11.0 (♂),10.0 (♀) gm/dl&#xD;
&#xD;
          -  Participants with diabetes whose HgbA1c &gt;10.0%&#xD;
&#xD;
          -  Chronic alcohol (&gt;14 drinks ETOH a week) or drug (any cocaine, methamphetamine, and&#xD;
             cannabis ≥4 x week) dependency&#xD;
&#xD;
          -  Allergy to lidocaine and red dye&#xD;
&#xD;
          -  Chronic use of oral corticosteroids or other medications that affect muscle function&#xD;
&#xD;
          -  Current use of organic nitrates or phosphodiesterase type 5 (PDE5) inhibitors&#xD;
&#xD;
          -  Unable to hold warfarin, direct-acting oral anticoagulants (DOACs), non-steroidal&#xD;
             anti-inflammatory medications (NSAIDs) or aspirin for 3 days prior to muscle biopsy,&#xD;
             or to hold thienopyridine medications for 5 days prior to muscle biopsy. Participants&#xD;
             unable or unwilling to hold will follow the modified ASA hold plan&#xD;
&#xD;
          -  Any bleeding disorder that would contraindicate biopsy such as history of clinically&#xD;
             significant bleeding diathesis (e.g., Hemophilia A or B, Von Willebrand's Disease or&#xD;
             congenital Factor VII deficiency)&#xD;
&#xD;
          -  Unstable psychiatric diagnosis that would affect adherence and ability to complete the&#xD;
             protocol&#xD;
&#xD;
          -  Dementia or inability to give informed consent or follow study protocol&#xD;
&#xD;
          -  End-stage disease&#xD;
&#xD;
          -  Other chronic unstable disease such as active neoplasm, end stage chronic kidney,&#xD;
             liver or other organ disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>70 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Tara S Stakich, RN</last_name>
    <phone>412-864-2082</phone>
    <email>TSS54@pitt.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Daniel E Forman, MD</last_name>
    <phone>412-864-2507</phone>
    <email>Formand@pitt.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tara Stakich</last_name>
      <phone>412-864-2082</phone>
      <email>tss54@pitt.edu</email>
    </contact>
    <contact_backup>
      <last_name>Tara Stakich</last_name>
      <phone>4128642082</phone>
      <email>tss54@pitt.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Daniel E Forman, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>April 15, 2019</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>March 29, 2023</last_update_submitted>
  <last_update_submitted_qc>March 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Daniel Forman, MD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>70 and Older</keyword>
  <keyword>Bioenergetics</keyword>
  <keyword>Frailty</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Frailty</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-Identified data may be shared with other future investigators as research questions arise.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>A limit in time frame of sharing has not been defined.</ipd_time_frame>
    <ipd_access_criteria>Only de-identified data approved for sharing by PI.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04405180
org study id: STUDY20110334
secondary id: R01AG058883
nct id: NCT04405180
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This 2-site randomized double blinded controlled trial is to confirm and more definitively
      clarify the impact of a 12-week course of nitrite versus placebo on mitochondrial
      bioenergetics in older sedentary adults. This investigator will take an integrative
      physiology approach to determine the effect of nitrite therapy on a comprehensive assessment
      of mitochondrial energetics, skeletal muscle vascular function, and whole body physical
      function (cardiorespiratory function, exercise endurance, strength, balance, and physical
      activity) and fatigability.
Old age is associated with declining skeletal muscle mitochondrial bioenergetics with related
      decrements in cardiorespiratory fitness (CRF) and physical function that predispose to
      frailty, disability, and diminished quality of life. While exercise training may moderate and
      possibly even reverse declines in mitochondrial bioenergetics, potential for such benefit is
      typically confounded by exercise intolerance with early fatigability that results from the
      same age-related mitochondrial declines. Consequently, sedentariness is endemic and insidious
      among the growing population of older adults. This trial is to study the utility of inorganic
      nitrite salts as a novel means to modify this detrimental pattern. Classic studies
      demonstrate that nitrite facilitates hypoxic vasodilation in muscle. This investigator's
      preliminary data suggests that nitrite treatment also augments skeletal muscle mitochondrial
      bioenergetics in older adults. This investigator proposes improving mitochondrial function
      will also be reflected in clinical parameters, including CRF as well as broader functional
      attributes (endurance, strength, and balance) that enable physical activity (PA) and
      opportunity to mitigate frailty and disability. As such, this application is in line with the
      National Institute on Aging's mission to develop targeted interventions to prevent and treat
      age-associated conditions. This multi-disciplinary team has published seminal work indicating
      that mitochondrial bioenergetics and CRF are significant determinants of physical function in
      older adults. In parallel efforts, this investigative team showed efficacy of chronic nitrite
      therapy to improve mitochondrial bioenergetics in older sedentary adults. Only one month of
      nitrite therapy significantly improved ex vivo assessments of mitochondrial energetics in
      skeletal muscle biopsies, concomitant with increased skeletal muscle sirtuin-3 expression, a
      nicotinamide adenine dinucleotide (NAD) dependent lysine deacetylase and key regulator of
      mitochondrial metabolism. These key data reinforce the premise that nitrite enhances vital
      mitochondrial metabolism in older adults. Moreover, improvement in muscle energetics in
      nitrite-treated older adults was linked with increased exercise efficiency as evidenced by
      reduced oxygen consumption (VO2) during submaximal steady-state walking. This data supports
      the hypothesis that nitrite will make physical function easier such that physical activity
      will increase.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Parallel assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Quadruple: Participant, Care Provider, Investigator, Outcome Assessor
measure: Skeletal muscle mitochondrial respiration State 3, Baseline to 12-week change
time frame: 12-week course of study drug supplementation, up to 16 weeks total
description: We will use high resolution respirometry via Oroboros Oxygraph 2k to assess the effects of 12 weeks of inorganic nitrite vs placebo on skeletal muscle mitochondrial respiration from samples obtained via vastus lateralis muscle biopsy.
measure: Skeletal Muscle adenosine triphosphate (ATP) production, Baseline to 12-week change
time frame: 12-week course of study drug supplementation, up to 16 weeks total
description: Using phosphorus-magnetic resonance spectroscopy, we will measure ATP production and how it will change after 12 weeks (up to 16 weeks) of inorganic nitrite supplementation vs placebo.
measure: Change in cross-sectional area for each fiber type by skeletal muscle microscopy, Baseline to 12-week change
time frame: 12-week course of study drug supplementation, up to 16 weeks total
description: Using microscopy and immmunofluorescence, we will measure the cross-sectional area for each fiber type, relative fiber type number, and relative area composition of each muscle fiber type and mitochondrial content (area/section) after 12 weeks of inorganic nitrite supplementation vs placebo.
measure: Change in relative fiber type number by skeletal muscle microscopy, Baseline to 12-week change
time frame: 12-week course of study drug supplementation, up to 16 weeks total
description: Using microscopy and immmunofluorescence, we will measure the cross-sectional area for each fiber type, relative fiber type number, and relative area composition of each muscle fiber type and mitochondrial content (area/section) after 12 weeks of inorganic nitrite supplementation vs placebo.
measure: Change in relative area composition of each muscle fiber type by skeletal muscle microscopy, Baseline to 12-week change
time frame: 12-week course of study drug supplementation, up to 16 weeks total
description: Using microscopy and immmunofluorescence, we will measure the cross-sectional area for each fiber type, relative fiber type number, and relative area composition of each muscle fiber type and mitochondrial content (area/section) after 12 weeks of inorganic nitrite supplementation vs placebo.
measure: Change in mitochondrial content (area/section) by skeletal muscle microscopy, Baseline to 12-week change
time frame: 12-week course of study drug supplementation, up to 16 weeks total
description: Using microscopy and immmunofluorescence, we will measure the cross-sectional area for each fiber type, relative fiber type number, and relative area composition of each muscle fiber type and mitochondrial content (area/section) after 12 weeks of inorganic nitrite supplementation vs placebo.
measure: Baseline to 12-week change in Peak oxygen uptake (VO2) achieved during progressive resistance exercise testing
time frame: 12-week course of study drug supplementation, up to 16 weeks total
description: We will measure changes in cardiorespiratory fitness including Peak oxygen uptake (VO2) achieved during progressive resistance exercise testing (Increased VO2 notes increased oxygen uptake).
These will be assessed before and after 12 weeks (16 weeks total) of oral inorganic nitrite supplementation vs placebo.
measure: Baseline to 12-week change in VO2 during steady state exercise
time frame: 12-week course of study drug supplementation, up to 16 weeks total
description: We will measure changes in cardiorespiratory fitness including VO2 during steady state exercise (Increased VO2 notes increased oxygen uptake).
These will be assessed before and after 12 weeks (16 weeks total) of oral inorganic nitrite supplementation vs placebo.
measure: Baseline to 12-week change in duration of constant work rate exercise
time frame: 12-week course of study drug supplementation, up to 16 weeks total
description: We will measure changes in cardiorespiratory fitness including duration of constant work rate exercise (longer times denote increased exercise capacity).
These will be assessed before and after 12 weeks (16 weeks total) of oral inorganic nitrite supplementation vs placebo.
measure: Baseline to 12-week change in time of 400 m corridor walking
time frame: 12-week course of study drug supplementation, up to 16 weeks total
description: We will measure changes in cardiorespiratory fitness including time of 400 m corridor walking (decreased time denote increased exercise capacity).
These will be assessed before and after 12 weeks (16 weeks total) of oral inorganic nitrite supplementation vs placebo.
measure: Baseline to 12-week change in fatiguability during Steady State walking
time frame: 12-week course of study drug supplementation, up to 16 weeks total
description: Using the Borg Rating of Perceived Exertion (units 6-20), we will measure how much fatiguing the steady-state walking test (at 1.5 mph) is to the participant. We will compare this to the RPE of this test again after 12-weeks (up to 16-weeks) of inorganic nitrite supplementation vs placebo. Lower RPE notes improvement.
measure: Short Physical Performance Battery, Baseline to 12-week change
time frame: 12-week course of study drug supplementation, up to 16 weeks total
description: Will assess SPPB Score and its change after 12-weeks (up to 16-weeks) of inorganic nitrite supplementation vs placebo. Higher score shows improvement.
measure: Handgrip Strength, Baseline to 12-week change
time frame: 12-week course of study drug supplementation, up to 16 weeks total
description: Will assess handgrip strength in the dominant hand, and its change after 12-weeks (up to 16-weeks) of inorganic nitrite supplementation vs placebo. Higher score shows improvement.
measure: Steps - Physical activity (accelerometry)
time frame: 12-week course of study drug supplementation, up to 16 weeks total
description: Using an Actigraph accelerometry device on the participant's wrist, will assess daily steps and its change with 12-weeks (up to 16-weeks) of inorganic nitrite supplementation vs placebo. Higher number of steps note improvement.
measure: Vector Magnitude Counts - Physical activity (accelerometry)
time frame: 12-week course of study drug supplementation, up to 16 weeks total
description: Using an Actigraph accelerometry device on the participant's wrist, will assess daily vector magnitude counts and its change with 12-weeks (up to 16-weeks) of inorganic nitrite supplementation vs placebo. Higher number of counts note improvement.
arm group label: 20 mg Sodium Nitrite TID Arm
arm group type: Experimental
description: Subject is to receive active study drug three times per day during treatment (12 weeks +/- 5 days) period and then after the treatment period (up to 16 weeks total).
arm group label: Placebo Control Arm
arm group type: Placebo Comparator
description: Subject is to receive placebo three times per day during treatment period (12 weeks +/- 5 days) and then after the treatment testing period (up to 16 weeks total).
intervention type: Drug
intervention name: Placebos
description: Oral placebo capsule at a dose of 20 mg administered three times per day, during the day.
arm group label: Placebo Control Arm
other name: Placebo
intervention type: Drug
intervention name: 20mg sodium nitrite tid
description: Oral, inorganic sodium nitrite capsule at a dose of 20 mg administered three times per day, during the day.
arm group label: 20 mg Sodium Nitrite TID Arm
criteria: 
gender: All
minimum age: 70 Years
maximum age: N/A
healthy volunteers: No
last name: Tara S Stakich, RN
phone: 412-864-2082
email: TSS54@pitt.edu
last name: Daniel E Forman, MD
phone: 412-864-2507
email: Formand@pitt.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Daniel Forman, MD
investigator title: Professor
mesh term: Frailty
sharing ipd: Yes
ipd description: De-Identified data may be shared with other future investigators as research questions arise.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: A limit in time frame of sharing has not been defined.
ipd access criteria: Only de-identified data approved for sharing by PI.