Phase 2 N=64 Randomized Quadruple-blind Treatment

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

Aging · Sedentary Lifestyle · Frailty

Bottom Line

View on ClinicalTrials.gov: NCT04405180 ↗

Enrolled (actual)

Serious AEs

1.6%

Results posted

Oct 2024

Primary outcome: Primary: Skeletal Muscle Mitochondrial Respiration State 3; Baseline to 12-week Change. — 2.2; -0.8 pmol O2/s/mg DW — p=0.9017

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Placebos (Drug); 20mg sodium nitrite tid (Drug)
Age: Older Adult · 70+ yrs
Sex: All
Sponsor: Gladwin, Mark, MD
Primary completion: Jul 2023

Outcome Measures

Outcome	Result	p-value
PRIMARY Skeletal Muscle Mitochondrial Respiration State 3; Baseline to 12-week Change.	2.2; -0.8	0.9017
SECONDARY Skeletal Muscle Adenosine Triphosphate (ATP) Production, Baseline to 12-week Change	0.0222; -0.0131	0.4215

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.

Eligibility Criteria

Inclusion Criteria

Age ≥70 years
Sedentary ( 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 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04405180). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.