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

• ClinicalTrials.gov Identifier: NCT03818802
• Recruitment Status: Recruiting
• First Posted: January 28, 2019
• Last Update Posted: April 19, 2024
• Sponsor: Mayo Clinic
• Information provided by (Responsible Party): Eduardo N. Chini, Mayo Clinic

Study Description

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.

Study Design

• 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
• Actual Study Start Date: September 16, 2019
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: December 2024

Arms and Interventions

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.

Outcome Measures

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.

Eligibility Criteria

• 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

Contacts and Locations

Contacts

Contact: Jeremy Smith, MD; 507-266-1944; smith.jeremy@mayo.edu

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

Locations

United States, Minnesota

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Jeremy Smith 507-266-1944 smith.jeremy@mayo.edu

Contact: Karina K Kanamori Mendes, MD 507-266-2173 mendes.karina@mayo.edu

Sponsors and Collaborators

Mayo Clinic

Investigators

• Principal Investigator: Eduardo N Chini, MD; Mayo Clinic

More Information

• Responsible Party: Eduardo N. Chini, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03818802
• Other Study ID Numbers: 18-000224
• First Posted: January 28, 2019
• Last Update Posted: April 19, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

Niacinamide; Niacin; Nicotinic Acids; Vitamin B Complex; Vitamins; Micronutrients; Physiological Effects of Drugs; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Vasodilator Agents