<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/NCT03754842</url>
  </required_header>
  <id_info>
    <org_study_id>AU2018-11-19</org_study_id>
    <nct_id>NCT03754842</nct_id>
  </id_info>
  <brief_title>Effect of Nicotinamide Riboside and Pterostilbene Supplementation on Muscle Regeneration in Elderly Humans</brief_title>
  <official_title>Effect of Nicotinamide Riboside and Pterostilbene Supplementation on Muscle Regeneration in Elderly Humans - A Randomized, Placebo-controlled, Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Copenhagen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Successful skeletal muscle regeneration depends on a functional pool of muscle stem cells,&#xD;
      termed satellite cells (SC). SC are in a quiescent state throughout adulthood, but undergo&#xD;
      multiple cycles of proliferation and self-renewal in response to muscle damage. During aging,&#xD;
      there is a loss of SC quiescence, and SC more readily enter an ageing-state impairing their&#xD;
      function.&#xD;
&#xD;
      Animal studies have revealed a common denominator for increasing SC function and activity,&#xD;
      namely Sirtuin activation. Natural stimulators of Sirtuins includes Nicotinamide Riboside&#xD;
      (NR) (a Nicotinamide adenine dinucleotide (NAD+) precursor) and the polyphenol Pterostilbene&#xD;
      (PT). In this study, we aim to investigate if NR+PT supplementation will promote skeletal&#xD;
      muscle regeneration after muscle damage in elderly humans by enhanced recruitment of SC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      14 days after start of placebo or NR/PT (500/100 mg twice daily) supplementation a muscle&#xD;
      damage will induced in the m. vastus lat. by electric stimulation combined with eccentric&#xD;
      work in a dynamometer. Muscle biopsies will be collected at 2 hours, 2, 8 and 30 days post&#xD;
      damage and placebo or NR/PT supplementation will continue for the whole study period (45&#xD;
      days).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 12, 2019</start_date>
  <completion_date type="Actual">September 1, 2020</completion_date>
  <primary_completion_date type="Actual">September 1, 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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Presence of Satellite Cells</measure>
    <time_frame>Change from baseline up to 45 days</time_frame>
    <description>quantified by immunohistochemistry in muscle biopsies</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Activation of Satellite cells</measure>
    <time_frame>Change from baseline up to 45 days</time_frame>
    <description>determined by immunohistochemistry and FACS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of macrophages</measure>
    <time_frame>Change from baseline up to 45 days</time_frame>
    <description>determined by immunohistochemistry and FACS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of Fibro/Adipogenic Progenitors</measure>
    <time_frame>Change from baseline up to 45 days</time_frame>
    <description>quantified by FACS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of damaged muscle fibers</measure>
    <time_frame>Change from baseline up to 45 days</time_frame>
    <description>determined by immunohistochemistry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of muscle regenerative fibers</measure>
    <time_frame>Change from baseline up to 45 days</time_frame>
    <description>determined by immunohistochemistry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of autophagy in relation to muscle damage</measure>
    <time_frame>Change from baseline up to 45 days</time_frame>
    <description>determined by Western blot and PCR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid accumulation in skeletal muscle tissue and liver</measure>
    <time_frame>Change from baseline to 8 days</time_frame>
    <description>determined by magnetic resonance spectroscopy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood glucose response in relation to muscle damage</measure>
    <time_frame>Change from baseline to 8 days</time_frame>
    <description>determined by Continuous glucose monitoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body composition (lean body mass and fat body mass)</measure>
    <time_frame>Change from baseline to 45 days</time_frame>
    <description>measured by Dual energy X-ray absorptiometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle strength</measure>
    <time_frame>Change from baseline up to 45 days</time_frame>
    <description>determined from maximal voluntary contraction of the m. quadriceps femoris</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Muscle Injury</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Nicotinamide Riboside + Pterostilbene</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo (twice daily)</intervention_name>
    <description>Matching placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Nicotinamide Riboside/Pterostilbene (500 mg/100 mg twice daily)</intervention_name>
    <description>Elysium Basis TM, Elysium Health, Inc., NY, USA</description>
    <arm_group_label>Nicotinamide Riboside + Pterostilbene</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written signed consent&#xD;
&#xD;
          -  Age: 55-80&#xD;
&#xD;
          -  BMI: 20-28 (kg/(m2))&#xD;
&#xD;
          -  Non-smoker&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Endocrine disease, neurological or muscle disease&#xD;
&#xD;
          -  Other severe disease&#xD;
&#xD;
          -  High daily activity level (&gt;30 min / day)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Aarhus University Hospital</name>
      <address>
        <city>Aarhus N</city>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 22, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>November 4, 2020</last_update_submitted>
  <last_update_submitted_qc>November 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Niacinamide</mesh_term>
    <mesh_term>Niacin</mesh_term>
    <mesh_term>Nicotinic Acids</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03754842
org study id: AU2018-11-19
nct id: NCT03754842
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Successful skeletal muscle regeneration depends on a functional pool of muscle stem cells,
      termed satellite cells (SC). SC are in a quiescent state throughout adulthood, but undergo
      multiple cycles of proliferation and self-renewal in response to muscle damage. During aging,
      there is a loss of SC quiescence, and SC more readily enter an ageing-state impairing their
      function.

      Animal studies have revealed a common denominator for increasing SC function and activity,
      namely Sirtuin activation. Natural stimulators of Sirtuins includes Nicotinamide Riboside
      (NR) (a Nicotinamide adenine dinucleotide (NAD+) precursor) and the polyphenol Pterostilbene
      (PT). In this study, we aim to investigate if NR+PT supplementation will promote skeletal
      muscle regeneration after muscle damage in elderly humans by enhanced recruitment of SC.
14 days after start of placebo or NR/PT (500/100 mg twice daily) supplementation a muscle
      damage will induced in the m. vastus lat. by electric stimulation combined with eccentric
      work in a dynamometer. Muscle biopsies will be collected at 2 hours, 2, 8 and 30 days post
      damage and placebo or NR/PT supplementation will continue for the whole study period (45
      days).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Presence of Satellite Cells
time frame: Change from baseline up to 45 days
description: quantified by immunohistochemistry in muscle biopsies
measure: Activation of Satellite cells
time frame: Change from baseline up to 45 days
description: determined by immunohistochemistry and FACS
measure: Presence of macrophages
time frame: Change from baseline up to 45 days
description: determined by immunohistochemistry and FACS
measure: Presence of Fibro/Adipogenic Progenitors
time frame: Change from baseline up to 45 days
description: quantified by FACS
measure: Presence of damaged muscle fibers
time frame: Change from baseline up to 45 days
description: determined by immunohistochemistry
measure: Presence of muscle regenerative fibers
time frame: Change from baseline up to 45 days
description: determined by immunohistochemistry
measure: Presence of autophagy in relation to muscle damage
time frame: Change from baseline up to 45 days
description: determined by Western blot and PCR
measure: Lipid accumulation in skeletal muscle tissue and liver
time frame: Change from baseline to 8 days
description: determined by magnetic resonance spectroscopy
measure: Blood glucose response in relation to muscle damage
time frame: Change from baseline to 8 days
description: determined by Continuous glucose monitoring
measure: Body composition (lean body mass and fat body mass)
time frame: Change from baseline to 45 days
description: measured by Dual energy X-ray absorptiometry
measure: Muscle strength
time frame: Change from baseline up to 45 days
description: determined from maximal voluntary contraction of the m. quadriceps femoris
arm group label: Placebo
arm group type: Placebo Comparator
arm group label: Nicotinamide Riboside + Pterostilbene
arm group type: Experimental
intervention type: Other
intervention name: Placebo (twice daily)
description: Matching placebo
arm group label: Placebo
intervention type: Other
intervention name: Nicotinamide Riboside/Pterostilbene (500 mg/100 mg twice daily)
description: Elysium Basis TM, Elysium Health, Inc., NY, USA
arm group label: Nicotinamide Riboside + Pterostilbene
criteria: 
gender: All
minimum age: 55 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Niacinamide
mesh term: Niacin
mesh term: Nicotinic Acids
sharing ipd: Undecided