- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04405180
Nitrites, Skeletal Muscle Mitochondrial Bioenergetics, and Physical Activity in Old Age (Nitrite)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Tara S Stakich, RN
- Phone Number: 412-864-2082
- Email: TSS54@pitt.edu
Study Contact Backup
- Name: Daniel E Forman, MD
- Phone Number: 412-864-2507
- Email: Formand@pitt.edu
Study Locations
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213
- University of Pittsburgh
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age ≥70 years
- Sedentary (<1 hour/week of volitional exercise activity)
- Clinically stable (euvolemic; baseline HR <100 bpm) and without hospitalization or invasive cardiac procedure for 6 weeks
Exclusion Criteria:
- Blood pressure <110 or >160/95 mmHg
- Orthopedic or other chronic condition which limits physical activity or exercise testing assessments
- If valve replacement has been performed, patient may not be enrolled for 12 months after this procedure
- Severe peripheral or pulmonary artery disease
- Anemia: Hgb <11.0 (♂),10.0 (♀) gm/dl
- Participants with diabetes whose HgbA1c >10.0%
- Chronic alcohol (>14 drinks ETOH a week) or drug (any cocaine, methamphetamine, and cannabis ≥4 x week) dependency
- Allergy to lidocaine and red dye
- Chronic use of oral corticosteroids or other medications that affect muscle function
- Current use of organic nitrates or phosphodiesterase type 5 (PDE5) inhibitors
- Unable to hold warfarin, direct-acting oral anticoagulants (DOACs), non-steroidal anti-inflammatory medications (NSAIDs) or aspirin for 3 days prior to muscle biopsy, or to hold thienopyridine medications for 5 days prior to muscle biopsy. Participants unable or unwilling to hold will follow the modified ASA hold plan
- Any bleeding disorder that would contraindicate biopsy such as history of clinically significant bleeding diathesis (e.g., Hemophilia A or B, Von Willebrand's Disease or congenital Factor VII deficiency)
- Unstable psychiatric diagnosis that would affect adherence and ability to complete the protocol
- Dementia or inability to give informed consent or follow study protocol
- End-stage disease
- Other chronic unstable disease such as active neoplasm, end stage chronic kidney, liver or other organ disease
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 20 mg Sodium Nitrite TID Arm
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).
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Oral, inorganic sodium nitrite capsule at a dose of 20 mg administered three times per day, during the day.
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Placebo Comparator: Placebo Control Arm
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).
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Oral placebo capsule at a dose of 20 mg administered three times per day, during the day.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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.
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12-week course of study drug supplementation, up to 16 weeks total
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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.
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12-week course of study drug supplementation, up to 16 weeks total
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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
|
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.
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12-week course of study drug supplementation, up to 16 weeks total
|
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
|
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.
|
12-week course of study drug supplementation, up to 16 weeks total
|
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
|
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.
|
12-week course of study drug supplementation, up to 16 weeks total
|
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
|
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.
|
12-week course of study drug supplementation, up to 16 weeks total
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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. |
12-week course of study drug supplementation, up to 16 weeks total
|
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
|
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. |
12-week course of study drug supplementation, up to 16 weeks total
|
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
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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. |
12-week course of study drug supplementation, up to 16 weeks total
|
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
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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. |
12-week course of study drug supplementation, up to 16 weeks total
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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
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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.
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12-week course of study drug supplementation, up to 16 weeks total
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Short Physical Performance Battery, Baseline to 12-week change
Time Frame: 12-week course of study drug supplementation, up to 16 weeks total
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Will assess SPPB Score and its change after 12-weeks (up to 16-weeks) of inorganic nitrite supplementation vs placebo.
Higher score shows improvement.
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12-week course of study drug supplementation, up to 16 weeks total
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Handgrip Strength, Baseline to 12-week change
Time Frame: 12-week course of study drug supplementation, up to 16 weeks total
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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.
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12-week course of study drug supplementation, up to 16 weeks total
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Steps - Physical activity (accelerometry)
Time Frame: 12-week course of study drug supplementation, up to 16 weeks total
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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.
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12-week course of study drug supplementation, up to 16 weeks total
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Vector Magnitude Counts - Physical activity (accelerometry)
Time Frame: 12-week course of study drug supplementation, up to 16 weeks total
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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.
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12-week course of study drug supplementation, up to 16 weeks total
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- STUDY20110334
- R01AG058883 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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