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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 53
- 试验地点
- 2
- 主要终点
- Respiration rate on muscle biopsy samples
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
盲法说明
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.
入排标准
- 年龄范围
- 65 Years 至 80 Years（Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy elderly female subjects between 65 and 80 years of age
排除标准
- •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
结局指标
主要结局
Respiration rate on muscle biopsy samples
时间窗: 6 months
The samples will be analyzed for respiration rate in isolated mitochondria and permeabilized fibers
Maximal oxygen uptake (VO2 max) test
时间窗: 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.
Short Physical Performance Battery (SPPB)
时间窗: 6 months
The SPPB captures domains of strength, endurance, and balance and is highly predictive of subsequent disability.
Skeletal muscle function
时间窗: 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.
PCR on muscle biopsy samples
时间窗: 6 months
RT-PCR for gene expression
Immunoblot on muscle biopsy samples
时间窗: 6 months
Immunoblot in skeletal lysates for protein expression
Bone metabolism
时间窗: 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.
次要结局
- Glucose profile(6 months)
- Insulin(6 months)
- Hemoglobin A1C(6 months)
- Lipid profile(6 months)
- Oral glucose tolerance test(6 months)
研究者
Eduardo N. Chini
Principal Investigator
Mayo Clinic