<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03283462</url>
  </required_header>
  <id_info>
    <org_study_id>17.01.AMZ</org_study_id>
    <secondary_id>1178231</secondary_id>
    <nct_id>NCT03283462</nct_id>
  </id_info>
  <brief_title>Bioenergetics and Muscle Function Improvement With AMAZ-02 in Elderly Skeletal Muscle (ENERGIZE Trial)</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amazentis SA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Synteract, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Amazentis SA</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, double-blind, single-center, placebo-controlled Phase 2 trial enrolling&#xD;
      66 healthy elderly subjects (33 placebo and 33 AMAZ-02 administration) who are ≥65 and ≤ 90&#xD;
      years of age with evidence of low mitochondrial function. AMAZ-02 or placebo will be orally&#xD;
      administered for 4 months.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 15, 2018</start_date>
  <completion_date type="Actual">October 28, 2020</completion_date>
  <primary_completion_date type="Actual">September 25, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in 6 minute walking distance (6MWD) at the end of study intervention compared to baseline</measure>
    <time_frame>4 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent change from baseline in ATP max (maximal ATP synthesis rate) in hand skeletal muscle (via Magnetic Resonance Spectroscopy)</measure>
    <time_frame>2, 4 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent change from baseline in contraction number during a hand muscle fatigue test</measure>
    <time_frame>2, 4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change from baseline in ATP max (maximum ATP synthesis rate) in leg skeletal muscle (via MRS)</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change from baseline in contraction number during a leg muscle fatigue test</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Short Physical Performance Battery (SPPB) scores at the end of study intervention compared to baseline</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in exercise tolerance compared to baseline (via cycle ergometry)</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in hand grip strength at the end of study intervention compared to baseline</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in leg muscle strength (1-RM and 10-RM) at the end of study intervention compared to baseline</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in muscle size (cross-sectional area of the muscles) at the end of study intervention compared to baseline</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in mitochondrial function on muscle biopsy samples at the end of study intervention compared to baseline (via respirometry)</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of AMAZ-02 on mitochondrial gene and protein expression in muscle tissue</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of AMAZ-02 on plasma acylcarnitines</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of AMAZ-02 on quality of life questionnaire (SF36)</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in plasma lipid profile</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in plasma for circulating biomarkers (myostatin, follistatin)</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Mitochondrial Function, Bioenergetics</condition>
  <condition>Muscle Function</condition>
  <condition>Aging</condition>
  <arm_group>
    <arm_group_label>Mitopure</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Mitopure</intervention_name>
    <description>Mitopure (Urolithin A) containing softgels</description>
    <arm_group_label>Mitopure</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo containing softgels</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adults ≥65 and ≤90 years of age&#xD;
&#xD;
          2. Able to travel to and from the University of Washington and Fred Hutch Cancer Research&#xD;
             Center (FHCRC)&#xD;
&#xD;
          3. Informed consent obtained&#xD;
&#xD;
          4. 6 minute walk distance of &lt;550 meters&#xD;
&#xD;
          5. ATP max &lt; 1mM /sec (in the hand FDI muscle)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects who have significant disease(s) or condition(s) which, in the opinion of the&#xD;
             investigator, may put the subject at risk because of their participation in the trial&#xD;
             or may influence either the results of the trial or the subject's ability to&#xD;
             participate in the trial&#xD;
&#xD;
          2. Hospitalization within 3 months for major atherosclerotic events (defined as combined&#xD;
             incidence of myocardial infarction, urgent target-vessel revascularization, coronary&#xD;
             bypass surgery and stroke) and for any hospitalization within 2 months.&#xD;
&#xD;
          3. Have any metal implants in the right limbs, including non-MRI compatible metal stents,&#xD;
             titanium pins/markers, etc.&#xD;
&#xD;
          4. Have an implanted cardiac pacemaker or other implanted non-MRI compatible cardiac&#xD;
             device&#xD;
&#xD;
          5. Chronic, uncontrolled hypertension as judged by the Investigator (i.e., Baseline SBP&#xD;
             &gt;150 mm Hg, DBP &gt;90 mm Hg) or a SBP &gt; 150 mm Hg or DBP &gt; 95 mm Hg at the time of&#xD;
             screening or baseline. If the initial BP reading is above these values, the reading&#xD;
             may be repeated one time within 20 minutes of the initial reading.&#xD;
&#xD;
          6. Body mass index &lt;18 or &gt;32 kg/m2&#xD;
&#xD;
          7. Severe chronic kidney disease requiring treatment with hemodialysis or peritoneal&#xD;
             dialysis.&#xD;
&#xD;
          8. Additional laboratory abnormalities determined as clinically significant by the&#xD;
             Investigator.&#xD;
&#xD;
          9. Clinically significant abnormalities on physical examination (as judged by the&#xD;
             Investigator)&#xD;
&#xD;
         10. Clinically significant and chronic uncontrolled renal, hepatic, pulmonary, endocrine,&#xD;
             neurologic disorders, bone, or gastrointestinal system dysfunction&#xD;
&#xD;
         11. History of seizures or epilepsy&#xD;
&#xD;
         12. History of serious mental illness as judged by the Investigator&#xD;
&#xD;
         13. Oral temperature &gt;37.5°C at the time of the physical&#xD;
&#xD;
         14. Suspicion, or recent history, of alcohol or substance abuse or tobacco use&#xD;
&#xD;
         15. Subjects who in the opinion of the Investigator have a clinically significant abnormal&#xD;
             12-lead ECG during the screening period. Presence of atrial fibrillation, varying&#xD;
             degrees of AV block, existence of a left bundle branch block, or evidence of previous&#xD;
             myocardial infarction.&#xD;
&#xD;
         16. Subjects who are either unwilling to agree to refrain from using or are found to be&#xD;
             using supplementary antioxidant vitamins (e.g., Coenzyme Q10, resveratrol,&#xD;
             L-carnitine) from 7 days prior to dosing and throughout the treatment period&#xD;
&#xD;
         17. Subjects who are either unwilling to agree to refrain from using or are found to be&#xD;
             using the following dietary restrictions (pomegranate juice, walnuts, pecans,&#xD;
             strawberry, raspberry blackberry) from 7 days prior to dosing and throughout the&#xD;
             treatment period&#xD;
&#xD;
         18. Are currently enrolled in a clinical trial involving an investigational product or&#xD;
             non-approved use of a drug or device or concurrently enrolled in any other type of&#xD;
             medical research judged not to be scientifically or medically compatible with this&#xD;
             study&#xD;
&#xD;
         19. Have participated, within the last 30 days from a clinical trial involving an&#xD;
             investigational product. If the previous investigational product has a long half life,&#xD;
             3 months or 5 half-lives (whichever is longer) should have passed&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Marcinek, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Washington</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jose Garcia, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>VA Puget Sound Health Care System</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Washington Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788244</url>
    <description>Related Info</description>
  </link>
  <results_reference>
    <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.</citation>
    <PMID>35050355</PMID>
  </results_reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>September 13, 2017</study_first_submitted>
  <study_first_submitted_qc>September 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>August 18, 2022</last_update_submitted>
  <last_update_submitted_qc>August 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03283462
org study id: 17.01.AMZ
secondary id: 1178231
nct id: NCT03283462
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in 6 minute walking distance (6MWD) at the end of study intervention compared to baseline
time frame: 4 months
measure: Percent change from baseline in ATP max (maximal ATP synthesis rate) in hand skeletal muscle (via Magnetic Resonance Spectroscopy)
time frame: 2, 4 months
measure: Percent change from baseline in contraction number during a hand muscle fatigue test
time frame: 2, 4 months
measure: Percent change from baseline in ATP max (maximum ATP synthesis rate) in leg skeletal muscle (via MRS)
time frame: 4 months
measure: Percent change from baseline in contraction number during a leg muscle fatigue test
time frame: 4 months
measure: Change in Short Physical Performance Battery (SPPB) scores at the end of study intervention compared to baseline
time frame: 4 months
measure: Change in exercise tolerance compared to baseline (via cycle ergometry)
time frame: 4 months
measure: Change in hand grip strength at the end of study intervention compared to baseline
time frame: 4 months
measure: Change in leg muscle strength (1-RM and 10-RM) at the end of study intervention compared to baseline
time frame: 4 months
measure: Change in muscle size (cross-sectional area of the muscles) at the end of study intervention compared to baseline
time frame: 4 months
measure: Change in mitochondrial function on muscle biopsy samples at the end of study intervention compared to baseline (via respirometry)
time frame: 4 months
measure: Effect of AMAZ-02 on mitochondrial gene and protein expression in muscle tissue
time frame: 4 months
measure: Effect of AMAZ-02 on plasma acylcarnitines
time frame: 4 months
measure: Effect of AMAZ-02 on quality of life questionnaire (SF36)
time frame: 4 months
measure: Change from baseline in plasma lipid profile
time frame: 4 months
measure: Change from baseline in plasma for circulating biomarkers (myostatin, follistatin)
time frame: 4 months
arm group label: Mitopure
arm group type: Active Comparator
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Dietary Supplement
intervention name: Mitopure
description: Mitopure (Urolithin A) containing softgels
arm group label: Mitopure
intervention type: Dietary Supplement
intervention name: Placebo
description: Placebo containing softgels
arm group label: Placebo
criteria: 
gender: All
minimum age: 65 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: David Marcinek, PhD
role: Principal Investigator
affiliation: University of Washington
last name: Jose Garcia, MD
role: Principal Investigator
affiliation: VA Puget Sound Health Care System
facility: 
country: United States
url: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788244
description: Related Info
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.
PMID: 35050355
responsible party type: Sponsor
sharing ipd: No