Clinical trial NCT03283462: Bioenergetics and Muscle Function Improvement With AMAZ-02 in Elderly Skeletal Muscle (ENERGIZE Trial)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mitochondrial Function, Bioenergetics
Muscle Function
Aging
Lead sponsor: Amazentis SA
Sponsor class: INDUSTRY
Collaborators: name: University of Washington
name: Synteract, Inc.
First posted: 2017-09-14
Enrollment: 66
Sex: ALL
Minimum age (years): 65
Maximum age (years): 90
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in 6 minute walking distance (6MWD) at the end of study intervention compared to baseline
timeFrame: 4 months
measure: Percent change from baseline in ATP max (maximal ATP synthesis rate) in hand skeletal muscle (via Magnetic Resonance Spectroscopy)
timeFrame: 2, 4 months
Secondary outcomes:
measure: Percent change from baseline in contraction number during a hand muscle fatigue test
timeFrame: 2, 4 months
measure: Percent change from baseline in ATP max (maximum ATP synthesis rate) in leg skeletal muscle (via MRS)
timeFrame: 4 months
measure: Percent change from baseline in contraction number during a leg muscle fatigue test
timeFrame: 4 months
measure: Change in Short Physical Performance Battery (SPPB) scores at the end of study intervention compared to baseline
timeFrame: 4 months
measure: Change in exercise tolerance compared to baseline (via cycle ergometry)
timeFrame: 4 months
measure: Change in hand grip strength at the end of study intervention compared to baseline
timeFrame: 4 months
measure: Change in leg muscle strength (1-RM and 10-RM) at the end of study intervention compared to baseline
timeFrame: 4 months
measure: Change in muscle size (cross-sectional area of the muscles) at the end of study intervention compared to baseline
timeFrame: 4 months
measure: Change in mitochondrial function on muscle biopsy samples at the end of study intervention compared to baseline (via respirometry)
timeFrame: 4 months
measure: Effect of AMAZ-02 on mitochondrial gene and protein expression in muscle tissue
timeFrame: 4 months
measure: Effect of AMAZ-02 on plasma acylcarnitines
timeFrame: 4 months
measure: Effect of AMAZ-02 on quality of life questionnaire (SF36)
timeFrame: 4 months
measure: Change from baseline in plasma lipid profile
timeFrame: 4 months
measure: Change from baseline in plasma for circulating biomarkers (myostatin, follistatin)
timeFrame: 4 months
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: University of Washington
name: David Marcinek, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: VA Puget Sound Health Care System
name: Jose Garcia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Liu S, D'Amico D, Shankland E, Bhayana S, Garcia JM, Aebischer P, Rinsch C, Singh A, Marcinek DJ. Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial. JAMA Netw Open. 2022 Jan 4;5(1):e2144279. doi: 10.1001/jamanetworkopen.2021.44279.