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

Healthy Elderly Volunteers Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03818802
• Other study ID #: 18-000224
• Status: Recruiting
• Phase: N/A
• Start date: September 16, 2019
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Mayo Clinic
• Contact: Jeremy Smith, MD
• Phone: 507-266-1944
• Email: smith.jeremy[@]mayo.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 65 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Elderly Volunteers

Intervention

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
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.

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal oxygen uptake (VO2 max) test	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.	6 months
Primary	Skeletal muscle function	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.	6 months
Primary	Short Physical Performance Battery (SPPB)	The SPPB captures domains of strength, endurance, and balance and is highly predictive of subsequent disability.	6 months
Primary	Respiration rate on muscle biopsy samples	The samples will be analyzed for respiration rate in isolated mitochondria and permeabilized fibers	6 months
Primary	PCR on muscle biopsy samples	RT-PCR for gene expression	6 months
Primary	Immunoblot on muscle biopsy samples	Immunoblot in skeletal lysates for protein expression	6 months
Primary	Bone metabolism	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.	6 months
Secondary	Glucose profile	Serum glucose measure	6 months
Secondary	Insulin	Serum insulin measure	6 months
Secondary	Lipid profile	Blood cholesterol measure	6 months
Secondary	Hemoglobin A1C	Hb A1C measure in blood sample	6 months
Secondary	Oral glucose tolerance test	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.	6 months