<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/NCT03818802</url>
  </required_header>
  <id_info>
    <org_study_id>18-000224</org_study_id>
    <nct_id>NCT03818802</nct_id>
  </id_info>
  <brief_title>Effects of Vitamin B3 Derivative Nicotinamide Riboside (NR) in Bone, Skeletal Muscle and Metabolic Functions in Aging</brief_title>
  <official_title>A Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Effects of Vitamin B3 Derivative Nicotinamide Riboside (NR) in Bone, Skeletal Muscle and Metabolic Functions in Aging</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</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>
      Researchers are trying to determine if the vitamin B3 derivative Nicotinamide Riboside (NR)&#xD;
      has any effects in bone, skeletal muscle, and metabolic functions and structure in aging.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objective: To assess the effect of &quot;NAD boosting&quot; through NR intake in skeletal&#xD;
      muscle and bone metabolism function, and biochemical evidence of improvement of DNA damage&#xD;
      repair in healthy elderly female patients with and without exercise.&#xD;
&#xD;
      Secondary Objective: To assess the effect of NR in metabolic functions of glucose and lipid&#xD;
      profile as well as to determine the safety of long term administration of NR in healthy&#xD;
      elderly female patients with and without exercise.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 16, 2019</start_date>
  <completion_date type="Anticipated">July 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>
    <intervention_model_description>The investigators will enroll 48 subjects (24 placebo vs. 24 NR) considering a dropout rate of 20%. Patients will be screened at outpatient clinic visit by the research team before the enrollment. For those subjects interested and qualified it will be offered participation in this trial. Once consent has been obtained baseline values will be established and subjects will begin treatment and followed for 4.5 months. After 4.5 months, a structured exercise regimen will be implemented in addition to the NR/placebo treatment and the patients will be followed for 6 weeks more, completing 6 months.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>This protocol will employ a blinded design so that the participant, study personnel, and investigators will not know subject group assignment status. The unblinding would be done by contacting the research pharmacy. While the safety of the subject always comes first, it is still important to seriously consider if unmasking/unblinding the study therapy is necessary to ensure a subject's safety. The unmasking/unblinding will happen only when there is a serious adverse event; in this case this event will be logged in the specific Case Report Form for Serious Adverse Event (SAE) that is part of this protocol. However, in cases where unmasking/unblinding was not associated with an SAE, such actions will be reported in a same timeline requirements for reporting of SAEs.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Maximal oxygen uptake (VO2 max) test</measure>
    <time_frame>6 months</time_frame>
    <description>Maximal oxygen uptake (VO2 max) test measures the maximum rate of oxygen consumption during incremental exercise (exercise of increasing intensity) and reflects the cardiorespiratory fitness of an individual and is an important determinant of their endurance capacity during prolonged exercise.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Skeletal muscle function</measure>
    <time_frame>6 months</time_frame>
    <description>The 6-minute walk test (6MWT) quantifies the distance a person can walk in six minutes and will be used to document the mobility/functional status of a patient. Originally developed to evaluate the physical capacity of patients with cardiopulmonary diseases, the test has been used to assess treatment effects, physical function status, and to predict morbidity and mortality in several patient populations including frail older adults.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Short Physical Performance Battery (SPPB)</measure>
    <time_frame>6 months</time_frame>
    <description>The SPPB captures domains of strength, endurance, and balance and is highly predictive of subsequent disability.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Respiration rate on muscle biopsy samples</measure>
    <time_frame>6 months</time_frame>
    <description>The samples will be analyzed for respiration rate in isolated mitochondria and permeabilized fibers</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PCR on muscle biopsy samples</measure>
    <time_frame>6 months</time_frame>
    <description>RT-PCR for gene expression</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Immunoblot on muscle biopsy samples</measure>
    <time_frame>6 months</time_frame>
    <description>Immunoblot in skeletal lysates for protein expression</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Bone metabolism</measure>
    <time_frame>6 months</time_frame>
    <description>Serum Carboxy-terminal Telopeptide (CTX), tartrate-resistant acid phosphatase isoform type 5b (TRAP5b), Amino-terminal Pro-peptide (P1NP), and osteocalcin will all be measured to monitor bone turnover markers.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Glucose profile</measure>
    <time_frame>6 months</time_frame>
    <description>Serum glucose measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin</measure>
    <time_frame>6 months</time_frame>
    <description>Serum insulin measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>6 months</time_frame>
    <description>Blood cholesterol measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin A1C</measure>
    <time_frame>6 months</time_frame>
    <description>Hb A1C measure in blood sample</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral glucose tolerance test</measure>
    <time_frame>6 months</time_frame>
    <description>An 18-gauge cannula will be inserted in a retrograde fashion into a dorsal hand vein of the non-dominant arm. The hand will be placed in a heated box (55°C) to enable sampling of arterialized venous blood. Blood will be drawn at 0 (baseline), 10, 20, 30, 60, 90, and 120 minutes for the measurement of glucose, insulin, and C-peptide concentrations. After the baseline blood draw, subjects will ingest 75 g of glucose over a period of 5 minutes.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">48</enrollment>
  <condition>Healthy Elderly Volunteers</condition>
  <arm_group>
    <arm_group_label>Nicotinamide Riboside</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>NR is a single chemical moiety containing nicotinamide and ribose. The investigational product is a synthetic NR that is nature-identical to naturally-occurring NR, does not induce flushing or pruritus and has no effect on lipid levels.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Correspondent placebo, a pill not containing the active component.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Nicotinamide Riboside</intervention_name>
    <description>It will be administered a total of 1000 mg/day of NR in a regimen of 500mg every 12 hours by mouth for 4.5 months. After 4.5 months, an advanced individual training (AIT) will be implemented in addition to administration of 1000mg/day (500mg every 12 hours) for 6 weeks more, completing total of 6 months.</description>
    <arm_group_label>Nicotinamide Riboside</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>It will be administered a correspondent placebo with the same shape and color as the active pill 12 hours by mouth for 4.5 months. After 4.5 months, an advanced individual training (AIT) will be implemented in addition to administration of correspondent placebo every 12 hours for 6 weeks more, completing total of 6 months.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy elderly female subjects between 65 and 80 years of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  General Exclusion Criteria&#xD;
&#xD;
               -  Subjects who participate in regular structured exercise more than 2 hours and 30&#xD;
                  min per week or 1hour and 15 min of vigorous exercise per week.&#xD;
&#xD;
               -  Unwilling to comply with the follow-up schedule&#xD;
&#xD;
               -  Inability or refusal to give informed consent by the patient&#xD;
&#xD;
               -  Subject who takes multivitamins containing vitamin B3 derivatives in a dose &gt; 200&#xD;
                  mg/day&#xD;
&#xD;
               -  Participation in another investigational drug study within 1 year of treatment&#xD;
&#xD;
          -  Laboratory Exclusion Criteria&#xD;
&#xD;
               -  Serum 25-hydroxyvitamin D &lt; 15 ng/ml&#xD;
&#xD;
               -  Serum phosphorus &gt; 5 mg/dL&#xD;
&#xD;
               -  Serum alkaline phosphatase 50% above normal limit&#xD;
&#xD;
               -  Serum aspartate transaminase 50% above normal limit&#xD;
&#xD;
               -  Serum calcium &gt; 10.5 mg/dL&#xD;
&#xD;
               -  Estimated Glomerular Filtration Rate (eGFR) &lt; 30 mL/min Creatinine Clearance &lt;&#xD;
                  50%&#xD;
&#xD;
               -  Poorly controlled Diabetes Mellitus (HbA1c&gt;8)&#xD;
&#xD;
          -  Clinical History Exclusion Criteria&#xD;
&#xD;
               -  Confirmed diagnosis of Diabetes Mellitus in use of insulin&#xD;
&#xD;
               -  Subjects presenting systolic BP&gt;180 mmHg or a diastolic BP&gt;90 mmHg on initial&#xD;
                  evaluation&#xD;
&#xD;
               -  Previous diagnosis of liver disease&#xD;
&#xD;
               -  Previous chronic kidney disease stages III and IV&#xD;
&#xD;
               -  Malignancy&#xD;
&#xD;
               -  Malabsorption syndrome&#xD;
&#xD;
               -  Hypo- or Hyperparathyroidism&#xD;
&#xD;
               -  Acromegaly&#xD;
&#xD;
               -  Cushing's syndrome&#xD;
&#xD;
               -  Hypopituitarism&#xD;
&#xD;
               -  Severe chronic obstructive pulmonary disease&#xD;
&#xD;
               -  Congestive heart failure&#xD;
&#xD;
               -  Musculoskeletal disorder&#xD;
&#xD;
               -  History of rheumatoid arthritis&#xD;
&#xD;
               -  Previous gastric bypass surgery&#xD;
&#xD;
               -  Clinical history of osteoporotic fracture (spine, hip, or distal forearm) within&#xD;
                  past year&#xD;
&#xD;
               -  Extreme of BMI (≤ 18.5 kg/m2 or ≥ 40 kg/m2)&#xD;
&#xD;
          -  Medication Exclusion Criteria&#xD;
&#xD;
               -  History of methotrexate therapy&#xD;
&#xD;
               -  History of denosumab therapy&#xD;
&#xD;
               -  History of oral or inhaled corticosteroid use &gt; 3 months&#xD;
&#xD;
               -  Current use of anticoagulants in general&#xD;
&#xD;
               -  Anticonvulsant therapy (within previous year)&#xD;
&#xD;
               -  Sodium fluoride (any history)&#xD;
&#xD;
               -  Treatment within the past 3 years with bisphosphonates&#xD;
&#xD;
               -  Treatment within the past 3 years with parathyroid hormone&#xD;
&#xD;
               -  Treatment within the past 3 years with calcitonin&#xD;
&#xD;
               -  Treatment within the past 3 years with estrogen&#xD;
&#xD;
               -  Treatment within the past 3 years with selective estrogen receptor modulator&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eduardo N Chini, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jeremy Smith, MD</last_name>
    <phone>507-266-1944</phone>
    <email>smith.jeremy@mayo.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Karina S Kanamori Mendes, MD</last_name>
    <phone>507-266-2173</phone>
    <email>Mendes.Karina@mayo.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jeremy Smith</last_name>
      <phone>507-266-1944</phone>
      <email>smith.jeremy@mayo.edu</email>
    </contact>
    <contact_backup>
      <last_name>Karina K Kanamori Mendes, MD</last_name>
      <phone>507-266-2173</phone>
      <email>mendes.karina@mayo.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>January 23, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>January 17, 2023</last_update_submitted>
  <last_update_submitted_qc>January 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Eduardo N. Chini</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>NAD boosting therapy</keyword>
  <keyword>Nicotinamide Riboside</keyword>
  <keyword>NAD precursors</keyword>
  <keyword>Aging</keyword>
  <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>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/NCT03818802
org study id: 18-000224
nct id: NCT03818802
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Researchers are trying to determine if the vitamin B3 derivative Nicotinamide Riboside (NR)
      has any effects in bone, skeletal muscle, and metabolic functions and structure in aging.
Primary Objective: To assess the effect of "NAD boosting" through NR intake in skeletal
      muscle and bone metabolism function, and biochemical evidence of improvement of DNA damage
      repair in healthy elderly female patients with and without exercise.

      Secondary Objective: To assess the effect of NR in metabolic functions of glucose and lipid
      profile as well as to determine the safety of long term administration of NR in healthy
      elderly female patients with and without exercise.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The investigators will enroll 48 subjects (24 placebo vs. 24 NR) considering a dropout rate of 20%. Patients will be screened at outpatient clinic visit by the research team before the enrollment. For those subjects interested and qualified it will be offered participation in this trial. Once consent has been obtained baseline values will be established and subjects will begin treatment and followed for 4.5 months. After 4.5 months, a structured exercise regimen will be implemented in addition to the NR/placebo treatment and the patients will be followed for 6 weeks more, completing 6 months.
primary purpose: Prevention
masking: Double (Participant, Investigator)
masking description: This protocol will employ a blinded design so that the participant, study personnel, and investigators will not know subject group assignment status. The unblinding would be done by contacting the research pharmacy. While the safety of the subject always comes first, it is still important to seriously consider if unmasking/unblinding the study therapy is necessary to ensure a subject's safety. The unmasking/unblinding will happen only when there is a serious adverse event; in this case this event will be logged in the specific Case Report Form for Serious Adverse Event (SAE) that is part of this protocol. However, in cases where unmasking/unblinding was not associated with an SAE, such actions will be reported in a same timeline requirements for reporting of SAEs.
measure: Maximal oxygen uptake (VO2 max) test
time frame: 6 months
description: Maximal oxygen uptake (VO2 max) test measures the maximum rate of oxygen consumption during incremental exercise (exercise of increasing intensity) and reflects the cardiorespiratory fitness of an individual and is an important determinant of their endurance capacity during prolonged exercise.
measure: Skeletal muscle function
time frame: 6 months
description: The 6-minute walk test (6MWT) quantifies the distance a person can walk in six minutes and will be used to document the mobility/functional status of a patient. Originally developed to evaluate the physical capacity of patients with cardiopulmonary diseases, the test has been used to assess treatment effects, physical function status, and to predict morbidity and mortality in several patient populations including frail older adults.
measure: Short Physical Performance Battery (SPPB)
time frame: 6 months
description: The SPPB captures domains of strength, endurance, and balance and is highly predictive of subsequent disability.
measure: Respiration rate on muscle biopsy samples
time frame: 6 months
description: The samples will be analyzed for respiration rate in isolated mitochondria and permeabilized fibers
measure: PCR on muscle biopsy samples
time frame: 6 months
description: RT-PCR for gene expression
measure: Immunoblot on muscle biopsy samples
time frame: 6 months
description: Immunoblot in skeletal lysates for protein expression
measure: Bone metabolism
time frame: 6 months
description: Serum Carboxy-terminal Telopeptide (CTX), tartrate-resistant acid phosphatase isoform type 5b (TRAP5b), Amino-terminal Pro-peptide (P1NP), and osteocalcin will all be measured to monitor bone turnover markers.
measure: Glucose profile
time frame: 6 months
description: Serum glucose measure
measure: Insulin
time frame: 6 months
description: Serum insulin measure
measure: Lipid profile
time frame: 6 months
description: Blood cholesterol measure
measure: Hemoglobin A1C
time frame: 6 months
description: Hb A1C measure in blood sample
measure: Oral glucose tolerance test
time frame: 6 months
description: An 18-gauge cannula will be inserted in a retrograde fashion into a dorsal hand vein of the non-dominant arm. The hand will be placed in a heated box (55°C) to enable sampling of arterialized venous blood. Blood will be drawn at 0 (baseline), 10, 20, 30, 60, 90, and 120 minutes for the measurement of glucose, insulin, and C-peptide concentrations. After the baseline blood draw, subjects will ingest 75 g of glucose over a period of 5 minutes.
arm group label: Nicotinamide Riboside
arm group type: Active Comparator
description: NR is a single chemical moiety containing nicotinamide and ribose. The investigational product is a synthetic NR that is nature-identical to naturally-occurring NR, does not induce flushing or pruritus and has no effect on lipid levels.
arm group label: Placebo
arm group type: Placebo Comparator
description: Correspondent placebo, a pill not containing the active component.
intervention type: Dietary Supplement
intervention name: Nicotinamide Riboside
description: It will be administered a total of 1000 mg/day of NR in a regimen of 500mg every 12 hours by mouth for 4.5 months. After 4.5 months, an advanced individual training (AIT) will be implemented in addition to administration of 1000mg/day (500mg every 12 hours) for 6 weeks more, completing total of 6 months.
arm group label: Nicotinamide Riboside
intervention type: Dietary Supplement
intervention name: Placebo
description: It will be administered a correspondent placebo with the same shape and color as the active pill 12 hours by mouth for 4.5 months. After 4.5 months, an advanced individual training (AIT) will be implemented in addition to administration of correspondent placebo every 12 hours for 6 weeks more, completing total of 6 months.
arm group label: Placebo
criteria: 
gender: Female
gender based: Yes
minimum age: 65 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Eduardo N Chini, MD
role: Principal Investigator
affiliation: Mayo Clinic
last name: Jeremy Smith, MD
phone: 507-266-1944
email: smith.jeremy@mayo.edu
last name: Karina S Kanamori Mendes, MD
phone: 507-266-2173
email: Mendes.Karina@mayo.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Eduardo N. Chini
investigator title: Principal Investigator
mesh term: Niacinamide
mesh term: Niacin
mesh term: Nicotinic Acids
sharing ipd: No