Bioenergetics and Muscle Function Improvement With AMAZ-02 in Elderly Skeletal Muscle (ENERGIZE Trial)

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Impact of a Daily Dose of AMAZ-02, a Food Derived Ingredient, for 4 Months on Skeletal Muscle Energetics and Function in Healthy Elderly

Conditions
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Mitochondrial Function, Bioenergetics, Muscle Function, Aging

Intervention / Treatment
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* Dietary Supplement: Mitopure
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥65 and ≤90 years of age Able to travel to and from the University of Washington and Fred Hutch Cancer Research Center (FHCRC) Informed consent obtained 6 minute walk distance of <550 meters ATP max < 1mM /sec (in the hand FDI muscle) Exclusion Criteria: 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 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. Have any metal implants in the right limbs, including non-MRI compatible metal stents, titanium pins/markers, etc. Have an implanted cardiac pacemaker or other implanted non-MRI compatible cardiac device 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. Body mass index <18 or >32 kg/m2 Severe chronic kidney disease requiring treatment with hemodialysis or peritoneal dialysis. Additional laboratory abnormalities determined as clinically significant by the Investigator. Clinically significant abnormalities on physical examination (as judged by the Investigator) Clinically significant and chronic uncontrolled renal, hepatic, pulmonary, endocrine, neurologic disorders, bone, or gastrointestinal system dysfunction History of seizures or epilepsy History of serious mental illness as judged by the Investigator Oral temperature >37.5°C at the time of the physical Suspicion, or recent history, of alcohol or substance abuse or tobacco use 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. 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 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 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 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

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mitopure<br> | Dietary Supplement: Mitopure<br>* Mitopure (Urolithin A) containing softgels<br>|
| Placebo Comparator: Placebo<br> | Dietary Supplement: Placebo<br>* Placebo containing softgels<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 exercise tolerance compared to baseline (via cycle ergometry) |  | 4 months | 
| Change in hand grip strength 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 mitochondrial function on muscle biopsy samples at the end of study intervention compared to baseline (via respirometry) |  | 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 |