Aging, Mitochondrial Function, Bioenergetics, Muscle Function
Conditions
Brief summary
This is a randomized, double-blind, single-center, placebo-controlled Phase 2 trial enrolling 66 healthy elderly subjects (33 placebo and 33 AMAZ-02 administration) who are ≥65 and ≤ 90 years of age with evidence of low mitochondrial function. AMAZ-02 or placebo will be orally administered for 4 months.
Interventions
DIETARY_SUPPLEMENTMitopure
Mitopure (Urolithin A) containing softgels
DIETARY_SUPPLEMENTPlacebo
Placebo containing softgels
Sponsors
University of Washington
Synteract, Inc.
Amazentis SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
1. Adults ≥65 and ≤90 years of age 2. Able to travel to and from the University of Washington and Fred Hutch Cancer Research Center (FHCRC) 3. Informed consent obtained 4. 6 minute walk distance of \<550 meters 5. ATP max \< 1mM /sec (in the hand FDI muscle)
Exclusion criteria
1. Subjects who have significant disease(s) or condition(s) which, in the opinion of the investigator, may put the subject at risk because of their participation in the trial or may influence either the results of the trial or the subject's ability to participate in the trial 2. Hospitalization within 3 months for major atherosclerotic events (defined as combined incidence of myocardial infarction, urgent target-vessel revascularization, coronary bypass surgery and stroke) and for any hospitalization within 2 months. 3. Have any metal implants in the right limbs, including non-MRI compatible metal stents, titanium pins/markers, etc. 4. Have an implanted cardiac pacemaker or other implanted non-MRI compatible cardiac device 5. Chronic, uncontrolled hypertension as judged by the Investigator (i.e., Baseline SBP \>150 mm Hg, DBP \>90 mm Hg) or a SBP \> 150 mm Hg or DBP \> 95 mm Hg at the time of screening or baseline. If the initial BP reading is above these values, the reading may be repeated one time within 20 minutes of the initial reading. 6. Body mass index \<18 or \>32 kg/m2 7. Severe chronic kidney disease requiring treatment with hemodialysis or peritoneal dialysis. 8. Additional laboratory abnormalities determined as clinically significant by the Investigator. 9. Clinically significant abnormalities on physical examination (as judged by the Investigator) 10. Clinically significant and chronic uncontrolled renal, hepatic, pulmonary, endocrine, neurologic disorders, bone, or gastrointestinal system dysfunction 11. History of seizures or epilepsy 12. History of serious mental illness as judged by the Investigator 13. Oral temperature \>37.5°C at the time of the physical 14. Suspicion, or recent history, of alcohol or substance abuse or tobacco use 15. Subjects who in the opinion of the Investigator have a clinically significant abnormal 12-lead ECG during the screening period. Presence of atrial fibrillation, varying degrees of AV block, existence of a left bundle branch block, or evidence of previous myocardial infarction. 16. Subjects who are either unwilling to agree to refrain from using or are found to be using supplementary antioxidant vitamins (e.g., Coenzyme Q10, resveratrol, L-carnitine) from 7 days prior to dosing and throughout the treatment period 17. Subjects who are either unwilling to agree to refrain from using or are found to be using the following dietary restrictions (pomegranate juice, walnuts, pecans, strawberry, raspberry blackberry) from 7 days prior to dosing and throughout the treatment period 18. Are currently enrolled in a clinical trial involving an investigational product or non-approved use of a drug or device or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study 19. Have participated, within the last 30 days from a clinical trial involving an investigational product. If the previous investigational product has a long half life, 3 months or 5 half-lives (whichever is longer) should have passed
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in 6 minute walking distance (6MWD) at the end of study intervention compared to baseline | 4 months |
| Percent change from baseline in ATP max (maximal ATP synthesis rate) in hand skeletal muscle (via Magnetic Resonance Spectroscopy) | 2, 4 months |
Secondary
| Measure | Time frame |
|---|---|
| Percent change from baseline in contraction number during a hand muscle fatigue test | 2, 4 months |
| Percent change from baseline in ATP max (maximum ATP synthesis rate) in leg skeletal muscle (via MRS) | 4 months |
| Percent change from baseline in contraction number during a leg muscle fatigue test | 4 months |
| Change in Short Physical Performance Battery (SPPB) scores at the end of study intervention compared to baseline | 4 months |
| Change in leg muscle strength (1-RM and 10-RM) at the end of study intervention compared to baseline | 4 months |
| Change in muscle size (cross-sectional area of the muscles) at the end of study intervention compared to baseline | 4 months |
| Change in exercise tolerance compared to baseline (via cycle ergometry) | 4 months |
| Effect of AMAZ-02 on mitochondrial gene and protein expression in muscle tissue | 4 months |
| Effect of AMAZ-02 on plasma acylcarnitines | 4 months |
| Effect of AMAZ-02 on quality of life questionnaire (SF36) | 4 months |
| Change from baseline in plasma lipid profile | 4 months |
| Change from baseline in plasma for circulating biomarkers (myostatin, follistatin) | 4 months |
| Change in mitochondrial function on muscle biopsy samples at the end of study intervention compared to baseline (via respirometry) | 4 months |
| Change in hand grip strength at the end of study intervention compared to baseline | 4 months |
Countries
United States
Outcome results
None listed