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

STUDY20110334

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.

2021-04-23

2023-07-14

2023-07-14

Completed

Early phase I

78

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

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2023-12-07