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Effects of Vitamin B3 Derivative Nicotinamide Riboside (NR) in Bone, Skeletal Muscle and Metabolic Functions in Aging

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ClinicalTrials.gov Identifier: NCT03818802
Recruitment Status : Recruiting
First Posted : January 28, 2019
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Eduardo N. Chini, Mayo Clinic

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Healthy Elderly Volunteers Dietary Supplement: Nicotinamide Riboside Dietary Supplement: Placebo Not Applicable

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
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.
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.
Primary Purpose: Prevention
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
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Nicotinamide Riboside
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.
Dietary Supplement: Nicotinamide Riboside
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.

Placebo Comparator: Placebo
Correspondent placebo, a pill not containing the active component.
Dietary Supplement: Placebo
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.




Primary Outcome Measures :
  1. Maximal oxygen uptake (VO2 max) test [ Time Frame: 6 months ]
    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.

  2. Skeletal muscle function [ Time Frame: 6 months ]
    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.

  3. Short Physical Performance Battery (SPPB) [ Time Frame: 6 months ]
    The SPPB captures domains of strength, endurance, and balance and is highly predictive of subsequent disability.

  4. Respiration rate on muscle biopsy samples [ Time Frame: 6 months ]
    The samples will be analyzed for respiration rate in isolated mitochondria and permeabilized fibers

  5. PCR on muscle biopsy samples [ Time Frame: 6 months ]
    RT-PCR for gene expression

  6. Immunoblot on muscle biopsy samples [ Time Frame: 6 months ]
    Immunoblot in skeletal lysates for protein expression

  7. Bone metabolism [ Time Frame: 6 months ]
    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.


Secondary Outcome Measures :
  1. Glucose profile [ Time Frame: 6 months ]
    Serum glucose measure

  2. Insulin [ Time Frame: 6 months ]
    Serum insulin measure

  3. Lipid profile [ Time Frame: 6 months ]
    Blood cholesterol measure

  4. Hemoglobin A1C [ Time Frame: 6 months ]
    Hb A1C measure in blood sample

  5. Oral glucose tolerance test [ Time Frame: 6 months ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   65 Years to 80 Years   (Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy elderly female subjects between 65 and 80 years of age

Exclusion Criteria:

  • General Exclusion Criteria

    • Subjects who participate in regular structured exercise more than 2 hours and 30 min per week or 1hour and 15 min of vigorous exercise per week.
    • Unwilling to comply with the follow-up schedule
    • Inability or refusal to give informed consent by the patient
    • Subject who takes multivitamins containing vitamin B3 derivatives in a dose > 200 mg/day
    • Participation in another investigational drug study within 1 year of treatment
  • Laboratory Exclusion Criteria

    • Serum 25-hydroxyvitamin D < 15 ng/ml
    • Serum phosphorus > 5 mg/dL
    • Serum alkaline phosphatase 50% above normal limit
    • Serum aspartate transaminase 50% above normal limit
    • Serum calcium > 10.5 mg/dL
    • Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min Creatinine Clearance < 50%
    • Poorly controlled Diabetes Mellitus (HbA1c>8)
  • Clinical History Exclusion Criteria

    • Confirmed diagnosis of Diabetes Mellitus in use of insulin
    • Subjects presenting systolic BP>180 mmHg or a diastolic BP>90 mmHg on initial evaluation
    • Previous diagnosis of liver disease
    • Previous chronic kidney disease stages III and IV
    • Malignancy
    • Malabsorption syndrome
    • Hypo- or Hyperparathyroidism
    • Acromegaly
    • Cushing's syndrome
    • Hypopituitarism
    • Severe chronic obstructive pulmonary disease
    • Congestive heart failure
    • Musculoskeletal disorder
    • History of rheumatoid arthritis
    • Previous gastric bypass surgery
    • Clinical history of osteoporotic fracture (spine, hip, or distal forearm) within past year
    • Extreme of BMI (≤ 18.5 kg/m2 or ≥ 40 kg/m2)
  • Medication Exclusion Criteria

    • History of methotrexate therapy
    • History of denosumab therapy
    • History of oral or inhaled corticosteroid use > 3 months
    • Current use of anticoagulants in general
    • Anticonvulsant therapy (within previous year)
    • Sodium fluoride (any history)
    • Treatment within the past 3 years with bisphosphonates
    • Treatment within the past 3 years with parathyroid hormone
    • Treatment within the past 3 years with calcitonin
    • Treatment within the past 3 years with estrogen
    • Treatment within the past 3 years with selective estrogen receptor modulator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03818802


Contacts
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Contact: Karina S Kanamori Mendes, MD 507-266-2173 Mendes.Karina@mayo.edu

Locations
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United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Karina S Kanamori Mendes, MD    507-266-2173    mendes.karina@mayo.edu   
Contact: Christine K Suby, RN    507-422-0746    suby.christine@mayo.edu   
Sponsors and Collaborators
Mayo Clinic
Investigators
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Principal Investigator: Eduardo N Chini, MD Mayo Clinic

Additional Information:
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Responsible Party: Eduardo N. Chini, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03818802     History of Changes
Other Study ID Numbers: 18-000224
First Posted: January 28, 2019    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eduardo N. Chini, Mayo Clinic:
NAD boosting therapy
Nicotinamide Riboside
NAD precursors
Aging
Additional relevant MeSH terms:
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Niacinamide
Niacin
Nicotinic Acids
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Vitamin B Complex
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents