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

Aging Clinical 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03283462
• Other study ID #: 17.01.AMZ
• Secondary ID: 1178231
• Status: Completed
• Phase: N/A
• Start date: February 15, 2018
• Est. completion date: October 28, 2020

Study information

• Verified date: October 2020
• Source: Amazentis SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: October 28, 2020
• Est. primary completion date: September 25, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Aging
• Mitochondrial Function, Bioenergetics
• Muscle Function

Intervention

Dietary Supplement:
• Mitopure
Mitopure (Urolithin A) containing softgels
• Placebo
Placebo containing softgels

Locations

Country	Name	City	State
United States	University of Washington Medical Center	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Amazentis SA	Synteract, Inc., University of Washington

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in 6 minute walking distance (6MWD) at the end of study intervention compared to baseline		4 months
Primary	Percent change from baseline in ATP max (maximal ATP synthesis rate) in hand skeletal muscle (via Magnetic Resonance Spectroscopy)		2, 4 months
Secondary	Percent change from baseline in contraction number during a hand muscle fatigue test		2, 4 months
Secondary	Percent change from baseline in ATP max (maximum ATP synthesis rate) in leg skeletal muscle (via MRS)		4 months
Secondary	Percent change from baseline in contraction number during a leg muscle fatigue test		4 months
Secondary	Change in Short Physical Performance Battery (SPPB) scores at the end of study intervention compared to baseline		4 months
Secondary	Change in exercise tolerance compared to baseline (via cycle ergometry)		4 months
Secondary	Change in hand grip strength at the end of study intervention compared to baseline		4 months
Secondary	Change in leg muscle strength (1-RM and 10-RM) at the end of study intervention compared to baseline		4 months
Secondary	Change in muscle size (cross-sectional area of the muscles) at the end of study intervention compared to baseline		4 months
Secondary	Change in mitochondrial function on muscle biopsy samples at the end of study intervention compared to baseline (via respirometry)		4 months
Secondary	Effect of AMAZ-02 on mitochondrial gene and protein expression in muscle tissue		4 months
Secondary	Effect of AMAZ-02 on plasma acylcarnitines		4 months
Secondary	Effect of AMAZ-02 on quality of life questionnaire (SF36)		4 months
Secondary	Change from baseline in plasma lipid profile		4 months
Secondary	Change from baseline in plasma for circulating biomarkers (myostatin, follistatin)		4 months

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