AMAZ-02 Effect on Exercise ToLerance in Healthy, Overweight Middle Aged Subjects (ATLAS Trial)

Study Overview
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Brief Summary
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This is a Phase 2 randomized, double-blind, placebo-controlled study enrolling 90 healthy, overweight, middle aged subjects (30 placebo, 30 low dose and 30 high dose AMAZ-02 intervention), 40-65 years of age, who are otherwise healthy. AMAZ-02, a food derived ingredient, will be given as a daily oral dose for 4 months.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy of AMAZ-02 on Muscle Function in Otherwise Healthy Middle-aged, Overweight and Inactive Individuals

Conditions
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Muscle Function, Mitochondrial Function, Overweight, Healthy Aging

Intervention / Treatment
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* Dietary Supplement: Mitopure 500mg
* Dietary Supplement: Mitopure 1000mg
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and females 40 to 65 years of age, inclusive Subjects who have not participated within the last 1 year in clinical trials focused on improving muscle function and physical performance Female participant is not of child bearing potential, defined as females who have had a hysterectomy or oophorectomy, bilateral tubal ligation or are post-menopausal (natural or surgically with > 1 year since last menstruation) or, Females of childbearing potential must agree to use a medically approved method of birth control and have a negative urine pregnancy test result. All hormonal birth control must have been in use for a minimum of three months. Acceptable methods of birth control include: Hormonal contraceptives including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (Depo-Provera, Lunelle), or hormone implant (Norplant System) Double-barrier method Intrauterine devices Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s) Vasectomy of partner (shown successful as per appropriate follow-up) Body mass index (BMI) between 25.0 and 34.9 kg/m2, inclusive Agree to avoid exercising 24 hours prior to study visits and maintain low physical activity status for the duration of the trial Agree to refrain from consumption of pomegranate juice and walnuts from 2 weeks prior to baseline and through the study period Agree to limit consumption of raspberries, strawberries and cloudberries from 2 weeks prior to baseline and through the study period Agree to refrain from using NSAIDs for 7-days prior to and following muscle sample collection Good general health to perform exercise testing safely, as determined by the Qualified Investigator based on medical history, physical examination, ECG and laboratory results Low VO2max defined as <35 ml/kg/min for males and <31 ml/kg/min for females as assessed by a submaximal cycle ergometer test Comprehension of the nature and purpose of the study including possible risks and side effects, and ability to communicate in person and by telephone in a manner that allows all protocol procedures to be carried out safely and reliably in the opinion of the investigative site staff Has given voluntary, written, informed consent to participate in the study Exclusion Criteria: Women who are pregnant, breast feeding, or planning to become pregnant during the trial Smokers or ex-smokers within the past 1 year from screening, including use of vaporizers or e-cigarettes Participation in another clinical study or receipt of an investigational drug within 60 days of the screening visit Blood donation within 1 month of baseline, as well as planned donation 1 month after end of study. Recent history (within the last 2 years) of alcohol or other substance abuse Use of medicinal marijuana. Unable to swallow capsules Regular participation in a structured exercise program with physical activity levels in Category 2 or higher defined as 20 min vigorous activity 3-times per week, moderate activity for 30 min 5 days per week or more Inability to abstain from intensive muscular effort Individuals who have engaged in 1 hour or more per week of resistance training in the past 3 months. Currently experiencing any medical condition that interferes with the ability to undergo physical strength testing during the study Recent participation in a weight loss diet, or loss >5% of total body weight within 3 months of randomization Clinically significant abnormal laboratory results at screening Allergy or sensitivity to test product ingredients (or closely related compounds) Allergy to anesthetic (Xylocaine, lidocaine) Soy allergy Inability to abstain from the consumption of pomegranate juice or walnuts Inability to abstain from frequent consumption of raspberries, strawberries or cloudberries Excessive consumption of beverages containing xanthine bases (>4 cups per day) such as coffee, tea, and cola Use of NHPs for the purposes of muscle building or function. Use of other NHPs must have been on a stable dosing regimen for at least a month prior to baseline and must maintain their current dosing regimen throughout the trial and must not begin taking any new NHPs throughout the trial; if the subject wishes to stop taking the NHP prior to beginning the trial they must do so at least 2 weeks prior to randomization. History of or current diagnosis of bleeding/blood disorder Use of oral anticoagulants (blood thinners), New Oral Anticoagulants (NOAC) or antiplatelet agents. Use of NSAID medications within one week before or after the needle muscle biopsy procedures. Use of steroid medications, current/recent (3 months) history of anabolic steroid, corticosteroid or estrogen use. Use of statins Use of thyroid medications. Asthma that has not been controlled with a stable regimen for a minimum of a year, or Asthma requiring the use of certain medications. Diagnosis of COPD Chronic myalgia, fibromyalgia or conditions characterized by regular muscle pain Metal fixation plates or screws from a previous surgery Clinically significant underlying systemic illness that may preclude the participant's ability to complete the trial or that may confound the study outcomes (i.e. terminal illnesses) Diagnosis of active cardiac or peripheral vascular disease SBP/DBP ≥150/95 mmHg without the use of hypertension medications, or SBP/DBP >140/90 mmHg with the use of hypertension medications. Diagnosed hyperlipidemia Renal or hepatic impairment or disease Any major diseases of the gastrointestinal, pulmonary or endocrine systems Type I and Type II diabetes Autoimmune disease or immuno-compromised (i.e. HIV positive, use of anti-rejection medication, rheumatoid arthritis, Hepatitis B/C positive) Diagnosis of chronic infectious disease Diagnosis of phenylketonuria Cancer, except skin cancers completely excised with no chemotherapy or radiation with a follow up that is negative. Participants with cancer in full remission for more than five years after diagnosis are acceptable if approved by QI. Significant neurological or psychiatric illness, including, but not limited to, Parkinson's disease and bipolar disorder as assessed by QI. History of seizures Individuals who are cognitively impaired and/or who are unable to give informed consent Any other condition which in the qualified investigator's opinion may adversely affect the participant's ability to complete the study or its measures or which may pose significant risk to the participant

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 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 500mg<br> | Dietary Supplement: Mitopure 500mg<br>* Mitopure containing softgels<br>|
| Active Comparator: Mitopure 1000mg<br> | Dietary Supplement: Mitopure 1000mg<br>* Mitopure containing softgels<br>|
| Active 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 exercise tolerance as assessed by power output on the cycle ergometer from baseline to day 120 between AMAZ-02 groups and placebo |  | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in exercise tolerance as assessed by power output on the cycle ergometer from baseline to day 60 between AMAZ-02 groups and placebo |  | 2 months | 
| Change in exercise tolerance as assessed by time to fatigue on the cycle ergometer from baseline to day 60 and from baseline to day 120 between AMAZ-02 groups and placebo |  | 2, 4 months | 
| Change in handgrip strength of the non-dominant hand as assessed by Jamar dynamometry from baseline to day 120 between AMAZ-02 groups and placebo |  | 4 months | 
| Change in isokinetic lower body muscle strength as assessed by the Biodex isokinetic dynamometer from baseline to day 120 between AMAZ-02 groups and placebo |  | 4 months | 
| Change in physical performance on the cycle ergometry defined as the time to reach 85% of maximum heart rate from baseline to days 60 and from baseline to day 120 between AMAZ-02 groups and placebo |  | 2, 4 months | 
| Change in distance walked in the 6-minute walk test as a measure of aerobic endurance from baseline to day 120 between AMAZ-02 groups and placebo |  | 4 months | 
| Change in gait speed from baseline to day 120 between AMAZ-02 groups and placebo as derived from the 6-minute walk test |  | 4 months | 
| Change in the 30-second chair stand test from baseline to day 120 between AMAZ-02 groups and placebo |  | 4 months | 
| Change from baseline to days 60 and from baseline to day 120 between AMAZ-02 groups and placebo in participant's quality of life as assessed by the 36-item short form (SF-36) questionnaire |  | 4 months | 
| Change from baseline to days 60 and from baseline to day 120 between AMAZ-02 groups and placebo in participant's perceived exertion during exercise testing as assessed by the Borg Rating of Perceived Exertion Scale (Scale from 6-20) |  | 2, 4 months | 
| Change from baseline to days 60 and 120 between AMAZ-02 groups and placebo in participant' resting energy expenditure in Kcal/ day via the Cardiocoach CO2 system |  | 2, 4 months | 
| Change in 3-day food records reviewed at baseline and days 60 and 120 |  | 2, 4 months | 
| Change from baseline to day 60 and from baseline to day 120 in serum lipid profile, insulin, and HbA1C between AMAZ-02 groups and placebo |  | 2, 4 months | 
| Change in lean body mass as assessed by dual X-ray absorptiometry (DXA) from baseline to day 120 between AMAZ-02 groups and placebo |  | 4 months | 
| Change in acylcarnitine profile in plasma via Metabolomics assessments from baseline to day 60, and from baseline to day 120 between AMAZ-02 groups and placebo |  | 2, 4 months | 
| Change in plasma muscle function biomarkers (myostatin, follistatin, inflammatory cytokines and mitokines) from baseline to day 60 and from baseline to day 120 between AMAZ-02 groups and placebo |  | 2, 4 months | 
| Change in in vivo mitochondrial gene expression from baseline to day 120 between AMAZ-02 groups and placebo as assessed via microarray performed on muscle biopsy |  | 4 months | 
| Change in the gut microbial diversity at baseline and at day 120 between AMAZ-02 groups and placebo assessed via 16s RNA sequencing performed on fecal samples |  | 4 months | 
| The change in the international physical activity questionnaire score (IPAQ) from baseline to day 120 between AMAZ-02 500mg/d and 1000mg/d and placebo. |  | 4 months |