- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04907110
NR Supplementation and Exercise
The Effects of Exercise Training Combined With NR Supplementation on Metabolic Health in Older Individuals
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Rationale: The number of age-related chronic diseases (like obesity, type 2 diabetes and cardiovascular diseases) is increasing rapidly worldwide, reaching pandemic proportions. These age-related chronic diseases are associated with metabolic disturbances and mitochondrial dysfunction in humans. Nicotinamide adenosine dinucleotide (NAD) levels play an important role in energy metabolism and mitochondrial functioning and indeed it has been shown that high concentrations of NAD+ as well as a high NAD+/NADH ratio are strongly associated with metabolic and mitochondrial health. In contrast, decreased NAD+ bioavailability is reported in both ageing and obese humans as well as in diabetic mice. These findings fueled the idea of influencing NAD+ bioavailability in order to improve metabolic disturbances and mitochondrial dysfunction in humans. Supplementation with nicotinamide riboside (NR), a naturally occurring form of vitamin B3, may provide a way to boost cellular NAD+ levels. However, in contrast to animal studies, NR supplementation in humans has so far been unsuccessful in improving skeletal muscle mitochondrial function, exercise capacity or insulin sensitivity. Recently, it has been suggested that a situation where NAD+ levels become limited, is needed for NR supplementation to exert beneficial health effects. This situation could be achieved by combining exercise and NR supplementation. However, studies combining NR and exercise are lacking, which is why we would like to perform such a study here.
Objective: The primary objective of this study is to determine whether combined treatment of exercise and NR imposes greater improvements in skeletal muscle mitochondrial metabolism in older humans compared to exercise treatment alone. The secondary objective is to determine whether combined treatment of exercise and NR supplementation imposes greater improvements in sleeping metabolic rate (SMR). As explorative objectives, we will examine whether combined treatment with exercise and NR imposes greater improvements in muscle (NAD) metabolites, energy metabolism and physical performance.
Study design: The present study is a randomized, double-blinded, placebo-controlled double arm longitudinal intervention study in a pre and post design.
Study population: 30 older male and (postmenopausal) female participants, aged 65 - 80 years with a BMI between 25-35 kg/m2 will perform this study (15 participants in the exercise+placebo group, 15 participants in the exercise+NR group). From experience with similar studies, we estimate a drop-out rate of 20% and a screening failure of 50% (due to the strict inclusion criteria), resulting in maximally 36 subjects that have to be included and 72 subjects that have to be screened (maximally).
Intervention (if applicable): Participants will be asked to take two pills of NR (250mg/pill), or placebo, twice daily (two with breakfast and two with diner, a total of 4 pills/day; 1000mg/day), for 40 days. During days 17-38 of the NR intervention, participants will perform a 3-weeks supervised exercise training program with four ~30 min exercise sessions per week (two endurance session on a bike at 70%Wmax and two high intensity interval (HIIT) sessions. Participants will be randomly assigned to the placebo + exercise or NR + exercise arm. To assess the outcomes, participants will undergo three test days before the start of the NR supplementation and repeat these three test days at the end (day 38-40) of NR supplementation.
Main study parameters/endpoints: The primary study endpoints is ex vivo skeletal muscle mitochondrial function measured via high-resolution respirometry. Explorative objectives are muscle (NAD) metabolites, energy metabolism and physical performance.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Maastricht, Netherlands, 6229 ER
- Maastricht University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Participants are able to provide signed and dated written informed consent prior to any study specific procedures
- Aged ≥ 65 and ≤ 80 years
- Body mass index (BMI) 25 - 35 kg/m2
- Stable dietary habits (no weight loss or gain > 5 kg in the past 3 months)
- No signs of active cardiovascular disease, liver or kidney malfunction
Exclusion Criteria:
- Type 2 diabetes
- Patients with congestive heart failure and and/or severe renal and or liver insufficiency
- Uncontrolled hypertension
- Any contra-indication for MRI scanning
- Alcohol consumption of >3 servings per day for man and >2 servings per day for woman
- Smoking
- Unstable body weight (weight gain or loss > 5kg in the last 3 months)
- Engagement in structured exercise activities > 2 hours a week
- Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator which would possibly hamper our study results
- Medication use known to hamper subject's safety during the study procedures
- Subjects who do not want to be informed about unexpected medical findings
- Use of food supplements containing NR or Resveratrol (similar working mechanisms)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Exercise + NR
Participants will be asked to take two pills of NR (250mg/pill) twice daily (a total of 4 pills/day; 1000mg/day), for 40 days.
During days 17-38 of the NR intervention, participants will perform a 3-weeks supervised exercise training program with four ~30 min exercise sessions per week (two endurance session on a bike at 70%Wmax and two high intensity interval (HIIT) sessions.
To assess the outcomes, participants will undergo three test days before the start of the NR supplementation and repeat these three test days at the end (day 38-40) of NR supplementation.
|
Participants in the NR supplementation + exercise group will undergo oral NR supplementation for 40 days.
NiagenTM is the name for the dietary supplement containing NR (ChromaDex, Inc.
Irvine, USA).
The total dosage of NR per day will be 1000mg.
This supplementation time of 40 days 1000mg/day
Other Names:
During days 17-38 of the NR/placebo intake, participants will perform a 3-weeks supervised exercise training program with four ~30 min exercise sessions per week (two endurance session on a bike at 70%Wmax and two high intensity interval (HIIT) sessions.
|
PLACEBO_COMPARATOR: Exercise + Placebo
Participants will be asked to take two pills of placebo, twice daily (a total of 4 pills/day), for 40 days.
During days 17-38 of the intervention, participants will perform a 3-weeks supervised exercise training program with four ~30 min exercise sessions per week (two endurance session on a bike at 70%Wmax and two high intensity interval (HIIT) sessions.
To assess the outcomes, participants will undergo three test days before the start of the NR supplementation and repeat these three test days at the end (day 38-40) of the placebo supplementation.
|
During days 17-38 of the NR/placebo intake, participants will perform a 3-weeks supervised exercise training program with four ~30 min exercise sessions per week (two endurance session on a bike at 70%Wmax and two high intensity interval (HIIT) sessions.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Ex vivo muscle mitochondrial function
Time Frame: Pre-intervention test day 3 + day 40 of the intervention NR/Placebo + exercise
|
Ex vivo mitochondrial function in skeletal muscle measured by oxygen consumption in muscle fibres (muscle biopsy vastus lateralis) on lipid-derived and carbohydrate-derived substrates.
|
Pre-intervention test day 3 + day 40 of the intervention NR/Placebo + exercise
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximal aerobic capacity
Time Frame: Pre-intervention test day 1 + Day 38
|
Maximal aerobic capacity measured during a VO2max cycling test in ml/kg/min
|
Pre-intervention test day 1 + Day 38
|
Physical performance
Time Frame: Pre-intervention test day 1 + Day 38
|
Physical performance is measured during a 6-minute walk test (6MWT) expressed as the distance covered during 6 minutes walking as well as the time necessary to stand up from a chair (TCST).
|
Pre-intervention test day 1 + Day 38
|
Skeletal muscle NAD concentrations (ex-vivo)
Time Frame: Pre-intervention test day 3 + Day 40
|
Skeletal muscle NAD metabolites are measured in muscle biopsies using metabolomics
|
Pre-intervention test day 3 + Day 40
|
Skeletal muscle NAD concentration (in-vivo)
Time Frame: Pre-intervention test day 3 + Day 40
|
Skeletal muscle NAD metabolites are measured in vivo using phosphorus magnetic resonance spectroscopy in the m.
vastus lateralis.
|
Pre-intervention test day 3 + Day 40
|
Intrahepatic lipid content
Time Frame: Pre-intervention test day 1 + Day 38
|
Intrahepatic lipid content is measured using proton magnetic resonance spectroscopy
|
Pre-intervention test day 1 + Day 38
|
Upper leg muscle mass
Time Frame: Pre-intervention test day 1 + Day 38
|
Upper leg muscle mass is measured with magnetic resonance imaging
|
Pre-intervention test day 1 + Day 38
|
Body composition
Time Frame: Pre-intervention test day 1 + Day 38
|
Body composition is measured using the BodPod technique and fat mass (kg and %) and fat-free mass (kg) will be determined.
|
Pre-intervention test day 1 + Day 38
|
Quality of life
Time Frame: Pre-intervention test day 1 + Day 38
|
Quality of life will be assessed by a questionnaire (in arbitrary units measured via the 32-item survey)
|
Pre-intervention test day 1 + Day 38
|
Blood metabolites
Time Frame: Pre-intervention test day 3 + Day 40
|
Metabolites in the blood (i.e.
glucose, free fatty acids, triglycerides, cholesterol, insulin in mmol/L taken via a venepuncture)
|
Pre-intervention test day 3 + Day 40
|
Submaximal exercise energy expenditure
Time Frame: Pre-intervention test day 3 + Day 40
|
Submaximal exercise energy expenditure will be measured via indirect calorimetry during a 60-minute submaximal cycling exercise at 50% Wmax
|
Pre-intervention test day 3 + Day 40
|
Sleeping metabolic rate
Time Frame: Pre-intervention test day 2 + Day 39
|
Sleeping metabolic rate will be measured during a 11 hour stay in a respiration chamber via indirect calorimetry
|
Pre-intervention test day 2 + Day 39
|
Exercise efficiency
Time Frame: Pre-intervention test day 3 + Day 40
|
Exercise efficiency will be measured during a 60-minute submaximal cycling test via indirect calorimetry in kJ/min
|
Pre-intervention test day 3 + Day 40
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NL77756.068.21
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Type 2 Diabetes
-
Antonio Di MauroCompletedType-2 DiabetesItaly
-
DiaMedica Therapeutics IncCompletedDiabetes Type 2Netherlands
-
RenJi HospitalUnknownType 2 Diabetes.China
-
University of Erlangen-Nürnberg Medical SchoolCompletedType 2-diabetesGermany
-
Chengdu Brilliant Pharmaceutical Co., Ltd.Not yet recruitingType 2 Diabetes Mellitus
-
Nanjing First Hospital, Nanjing Medical UniversityRecruitingType 2 Diabetes MellitusChina
-
Xiangya Hospital of Central South UniversityRecruitingType 2 Diabetes MellitusChina
-
University of Alabama at BirminghamCompletedType 2 Diabetes MellitusUnited States
-
Imperial College LondonAstraZeneca; Huma; North West London Collaboration of CCGs (NWL CCGs); Imperial...CompletedType 2 Diabetes MellitusUnited Kingdom
-
Universiti Sains MalaysiaCompleted
Clinical Trials on Niagen
-
KGK Science Inc.ChromaDex, Inc.CompletedPharmacokineticsCanada
-
KGK Science Inc.ChromaDex, Inc.Completed
-
ChromaDex, Inc.Midwest Center for Metabolic and Cardiovascular ResearchCompletedSleep | Cognitive Function | MoodUnited States
-
Franklin Health ResearchActive, not recruiting
-
Steven E Arnold, MDCompletedMild Cognitive Impairment | Cognitive Decline | Cognition Disorders in Old AgeUnited States
-
Charite University, Berlin, GermanyChromaDex, Inc.Recruiting
-
Iowa State UniversityCompleted
-
Massachusetts General HospitalCompletedCovid19 | Cognitive Symptom | Sequelae of; InfectionUnited States
-
University of Colorado, BoulderChromaDex, Inc.Completed
-
University of DelawareNational Institute on Aging (NIA)CompletedNAD Therapy for Improving Memory and Brain Blood Flow in Older Adults With Mild Cognitive ImpairmentMild Cognitive ImpairmentUnited States