search
Back to results

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

Primary Purpose

Muscle Function, Mitochondrial Function, Overweight, Healthy Aging

Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Mitopure 500mg
Mitopure 1000mg
Placebo
Sponsored by
Amazentis SA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Muscle Function, Mitochondrial Function

Eligibility Criteria

40 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Healthy males and females 40 to 65 years of age, inclusive
  2. Subjects who have not participated within the last 1 year in clinical trials focused on improving muscle function and physical performance

  3. 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)
  4. Body mass index (BMI) between 25.0 and 34.9 kg/m2, inclusive
  5. Agree to avoid exercising 24 hours prior to study visits and maintain low physical activity status for the duration of the trial
  6. Agree to refrain from consumption of pomegranate juice and walnuts from 2 weeks prior to baseline and through the study period
  7. Agree to limit consumption of raspberries, strawberries and cloudberries from 2 weeks prior to baseline and through the study period
  8. Agree to refrain from using NSAIDs for 7-days prior to and following muscle sample collection
  9. Good general health to perform exercise testing safely, as determined by the Qualified Investigator based on medical history, physical examination, ECG and laboratory results
  10. 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
  11. 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
  12. Has given voluntary, written, informed consent to participate in the study

Exclusion Criteria:

  1. Women who are pregnant, breast feeding, or planning to become pregnant during the trial
  2. Smokers or ex-smokers within the past 1 year from screening, including use of vaporizers or e-cigarettes
  3. Participation in another clinical study or receipt of an investigational drug within 60 days of the screening visit
  4. Blood donation within 1 month of baseline, as well as planned donation 1 month after end of study.
  5. Recent history (within the last 2 years) of alcohol or other substance abuse
  6. Use of medicinal marijuana.
  7. Unable to swallow capsules
  8. 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
  9. Inability to abstain from intensive muscular effort
  10. Individuals who have engaged in 1 hour or more per week of resistance training in the past 3 months.
  11. Currently experiencing any medical condition that interferes with the ability to undergo physical strength testing during the study
  12. Recent participation in a weight loss diet, or loss >5% of total body weight within 3 months of randomization
  13. Clinically significant abnormal laboratory results at screening
  14. Allergy or sensitivity to test product ingredients (or closely related compounds)
  15. Allergy to anesthetic (Xylocaine, lidocaine)
  16. Soy allergy
  17. Inability to abstain from the consumption of pomegranate juice or walnuts
  18. Inability to abstain from frequent consumption of raspberries, strawberries or cloudberries
  19. Excessive consumption of beverages containing xanthine bases (>4 cups per day) such as coffee, tea, and cola
  20. 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.
  21. History of or current diagnosis of bleeding/blood disorder
  22. Use of oral anticoagulants (blood thinners), New Oral Anticoagulants (NOAC) or antiplatelet agents.
  23. Use of NSAID medications within one week before or after the needle muscle biopsy procedures.
  24. Use of steroid medications, current/recent (3 months) history of anabolic steroid, corticosteroid or estrogen use.
  25. Use of statins
  26. Use of thyroid medications.
  27. Asthma that has not been controlled with a stable regimen for a minimum of a year, or Asthma requiring the use of certain medications.
  28. Diagnosis of COPD
  29. Chronic myalgia, fibromyalgia or conditions characterized by regular muscle pain
  30. Metal fixation plates or screws from a previous surgery
  31. 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)
  32. Diagnosis of active cardiac or peripheral vascular disease
  33. SBP/DBP ≥150/95 mmHg without the use of hypertension medications, or SBP/DBP >140/90 mmHg with the use of hypertension medications.
  34. Diagnosed hyperlipidemia
  35. Renal or hepatic impairment or disease
  36. Any major diseases of the gastrointestinal, pulmonary or endocrine systems
  37. Type I and Type II diabetes
  38. Autoimmune disease or immuno-compromised (i.e. HIV positive, use of anti-rejection medication, rheumatoid arthritis, Hepatitis B/C positive)
  39. Diagnosis of chronic infectious disease
  40. Diagnosis of phenylketonuria
  41. 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.
  42. Significant neurological or psychiatric illness, including, but not limited to, Parkinson's disease and bipolar disorder as assessed by QI.
  43. History of seizures
  44. Individuals who are cognitively impaired and/or who are unable to give informed consent
  45. 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

Sites / Locations

  • KGK Synergize Inc.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Mitopure 500mg

Mitopure 1000mg

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Change in exercise tolerance as assessed by power output on the cycle ergometer from baseline to day 120 between AMAZ-02 groups and placebo

Secondary Outcome Measures

Change in exercise tolerance as assessed by power output on the cycle ergometer from baseline to day 60 between AMAZ-02 groups and placebo
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
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
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
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
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
Change in gait speed from baseline to day 120 between AMAZ-02 groups and placebo as derived from the 6-minute walk test
Change in the 30-second chair stand test from baseline to day 120 between AMAZ-02 groups and placebo
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
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)
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
Change in 3-day food records reviewed at baseline and days 60 and 120
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
Change in lean body mass as assessed by dual X-ray absorptiometry (DXA) from baseline to day 120 between AMAZ-02 groups and placebo
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
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
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
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
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.

Full Information

First Posted
February 5, 2018
Last Updated
August 15, 2022
Sponsor
Amazentis SA
Collaborators
KGK Science Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT03464500
Brief Title
AMAZ-02 Effect on Exercise ToLerance in Healthy, Overweight Middle Aged Subjects (ATLAS Trial)
Acronym
ATLAS
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
March 6, 2018 (Actual)
Primary Completion Date
September 30, 2019 (Actual)
Study Completion Date
September 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amazentis SA
Collaborators
KGK Science Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscle Function, Mitochondrial Function, Overweight, Healthy Aging

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
90 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Mitopure 500mg
Arm Type
Active Comparator
Arm Title
Mitopure 1000mg
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Active Comparator
Intervention Type
Dietary Supplement
Intervention Name(s)
Mitopure 500mg
Intervention Description
Mitopure containing softgels
Intervention Type
Dietary Supplement
Intervention Name(s)
Mitopure 1000mg
Intervention Description
Mitopure containing softgels
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Placebo containing softgels
Primary Outcome Measure Information:
Title
Change in exercise tolerance as assessed by power output on the cycle ergometer from baseline to day 120 between AMAZ-02 groups and placebo
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Change in exercise tolerance as assessed by power output on the cycle ergometer from baseline to day 60 between AMAZ-02 groups and placebo
Time Frame
2 months
Title
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
Time Frame
2, 4 months
Title
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
Time Frame
4 months
Title
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
Time Frame
4 months
Title
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
Time Frame
2, 4 months
Title
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
Time Frame
4 months
Title
Change in gait speed from baseline to day 120 between AMAZ-02 groups and placebo as derived from the 6-minute walk test
Time Frame
4 months
Title
Change in the 30-second chair stand test from baseline to day 120 between AMAZ-02 groups and placebo
Time Frame
4 months
Title
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
Time Frame
4 months
Title
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)
Time Frame
2, 4 months
Title
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
Time Frame
2, 4 months
Title
Change in 3-day food records reviewed at baseline and days 60 and 120
Time Frame
2, 4 months
Title
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
Time Frame
2, 4 months
Title
Change in lean body mass as assessed by dual X-ray absorptiometry (DXA) from baseline to day 120 between AMAZ-02 groups and placebo
Time Frame
4 months
Title
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
Time Frame
2, 4 months
Title
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
Time Frame
2, 4 months
Title
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
Time Frame
4 months
Title
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
Time Frame
4 months
Title
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.
Time Frame
4 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mal Evans, PhD
Organizational Affiliation
KGK Science Inc.
Official's Role
Study Director
Facility Information:
Facility Name
KGK Synergize Inc.
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5R8
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
35584623
Citation
Singh A, D'Amico D, Andreux PA, Fouassier AM, Blanco-Bose W, Evans M, Aebischer P, Auwerx J, Rinsch C. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Rep Med. 2022 May 17;3(5):100633. doi: 10.1016/j.xcrm.2022.100633.
Results Reference
background
Links:
URL
https://pubmed.ncbi.nlm.nih.gov/35584623/
Description
Related Info

Learn more about this trial

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

We'll reach out to this number within 24 hrs