Nitrites, Skeletal Muscle Mitochondrial Bioenergetics, and Physical Activity in Old Age

• Status: Recruiting
• Trial end date: 2024-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gladwin, Mark, MD
• Collaborators: National Institute on Aging (NIA); National Institutes of Health (NIH)

Criteria

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

• 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