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Effect of Nicotinamide Riboside on Ketosis, Fat Oxidation & Metabolic Rate

Primary Purpose

Overweight, Obesity

Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Standard Diet
Ketogenic Diet
Placebo
Nicotinamide Riboside
Sponsored by
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Overweight focused on measuring Ketogenic Diet, Sleep, Energy Expenditure, Supplement, Calories

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: Meet one of the following: Adult males aged 18-65 years Pre-menopausal adult females aged 18-50 years Adult males aged 18-65 years with diagnosed maturity-onset diabetes of the young type 2 (MODY2) or pre-menopausal adult females aged 18-50 years with diagnosed MODY2 Weight stable (< +/- 5 % body weight change over past 6 months) as determined by volunteer report Body mass index (BMI) >= 25 kg/M^2 Able to cycle at a moderate rate and intensity with a HR equal to or greater than 0.3(SqrRoot) (220-age-HRest)+HRest but not exceeding 0.4(SqrRoot) (220-age-HRest)+HRest with no signs of arrhythmia EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: Taking prescription medications or other drugs or supplements that may influence energy metabolism or nutrient digestion or absorption (including, but not limited to, diet/weight loss medication or other medications at the discretion of the PI and/or study team) Indicators of liver disease; combination of both albumin < 2.8 mg/mL and bilirubin > 3 mg/Ml Individuals with significant medical comorbidities (e.g., non-MODY2 diabetes, NYHA Class >II heart failure, or CKD Stage II or worse, or American Society of Anesthesiologists Physical Status Class 3 or above) Individuals taking prescription medications to treat hypertension in participants without MODY2 Participating in a regular exercise program (> 2h/week of vigorous activity) as determined by volunteer report Positive pregnancy test (females only) Hematocrit < 40% (men only) Hematocrit <37% (women only) Caffeine consumption > 300 mg/day as determined by volunteer report Alcohol consumption > 3 drinks per day for men or > 2 drinks per day for women as determined by volunteer report Regular use of tobacco (smoking or chewing), e-cigarettes (a.k.a. vapes), nicotine patches, or illicit drugs over past 6 months as determined by volunteer report. Subjects may also be excluded based on a urine drug test. Psychological conditions as determined by volunteer report such as (but not limited to) eating disorders, depression, bipolar disorders, that would be incompatible with safe and successful participation in this study, as determined by investigators Volunteers with strict dietary concerns (e.g. vegetarian or kosher diet, food allergies) or a reported dislike of a significant fraction of the study foods Unwilling or unable to comply with or perform all study procedures (e.g. cycling or activities of daily living), or unavailability for the duration of the study, as determined by participant or investigator discretion Unwilling or unable to adhere to Lifestyle Considerations throughout study duration, as determined by participant or investigator discretion Volunteers unwilling or unable to give informed consent

Sites / Locations

  • National Institutes of Health Clinical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Men with overweight or obesity

MODY2 Patients

Women with overweight or obesity

Arm Description

To investigate whether NR supplementation augments the sleeping energy expenditure and fat oxidation rate during the ketogenic diet in men and women with overweight and obesity

To measure changes in sleeping energy expenditure and fat oxidation rate after transitioning from a baseline diet to an isocaloric ketogenic diet similar to our previous study in men

To investigate whether NR supplementation augments the sleeping energy expenditure and fat oxidation rate during the ketogenic diet in men and women with overweight and obesity

Outcomes

Primary Outcome Measures

Mean change in sleeping energy expenditure between the ketogenic diet and the baseline run-in diet
Mean change in sleeping energy expenditure measured by room calorimetry from 2 days of standard run-in diet to 5 days of ketogenic diet
Mean difference in sleeping energy expenditure between NR and placebo during the ketogenic diet
Mean difference in sleeping energy expenditure measured by room calorimetry during 5 days of ketogenic diet with NR supplementation or placebo

Secondary Outcome Measures

Mean change in sleeping fat oxidation rate between the ketogenic diet and the baseline run-in diet
Mean change in sleeping fat oxidation measured by room calorimetry from 2 days of standard run-in diet to 5 days of ketogenic diet
Mean difference in fat oxidation rate between NR and placebo during the ketogenic diet
Mean difference in sleeping fat oxidation measured by room calorimetry during 5 days of ketogenic diet with NR supplementation or placebo

Full Information

First Posted
September 19, 2023
Last Updated
October 24, 2023
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT06044935
Brief Title
Effect of Nicotinamide Riboside on Ketosis, Fat Oxidation & Metabolic Rate
Official Title
Effect of Nicotinamide Riboside on Ketosis, Fat Oxidation &Amp;Amp;Amp;Amp; Metabolic Rate
Study Type
Interventional

2. Study Status

Record Verification Date
September 18, 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 30, 2023 (Anticipated)
Primary Completion Date
January 31, 2026 (Anticipated)
Study Completion Date
January 31, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Background: At least 30% of Americans have fatty liver disease. This means that they store too much fat in the liver. At the moment lifestyle changes are the only way to treat this problem. Objective: To test how (1) a low-carbohydrate diet and (2) a supplement called nicotinamide riboside (NR) affect how a person s body uses dietary fat. Eligibility: Men aged 18 to 65 and women aged 18 to 50 who are healthy volunteers with a body mass index (height to weight ratio) of 25 or more. Adults with maturity-onset diabetes of the young type 2 (MODY2) are also needed. Design: Participants with diabetes will have 1 screening visit and a 9-day clinic stay. Healthy volunteers will have 1 screening visit and 2 clinic stays of 1 to 2 weeks each. During screening, all participants will have a physical exam with blood and urine tests. They will have their heart rhythm measured while riding a gym bike. NR is a pill taken by mouth. Only healthy volunteers will take the NR, for 14 days at a time, during 1 clinic stay. During their other stay, they will take placebos; these are pills that look like the study supplement but contain no NR. During each clinic stay, all participants will eat a normal American diet. Then they will eat a ketogenic low-carb diet for 5 days. Participants will have many tests, including: Sleeping every night and having two 24-hour stays in a special room that measures the gases their body uses and produces. Drinking a high-fat shake, then remaining seated for 5 hours while their blood and breath are monitored. Having a substance injected into the arm and remaining seated for 3 hours while their blood is measured. Wearing monitors to measure their activity levels. Another monitor will measure their blood glucose levels. Having imaging scans. ...
Detailed Description
Study Description: This is a randomized, double-blind, placebo-controlled crossover study of adults with overweight or obesity to determine whether nicotinamide riboside supplementation increases sleeping energy expenditure and fat oxidation rate during a ketogenic diet. Objectives: Primary Aim 1: Determine whether sleeping energy expenditure increases after transitioning to a low carbohydrate ketogenic diet as compared to a baseline high carbohydrate run-in diet in men Primary Aim 2: Determine whether sleeping energy expenditure is affected by NR supplementation during a ketogenic diet in men Secondary Aim 1: Determine whether fat oxidation during sleep increases after transitioning to a low carbohydrate ketogenic diet as compared to a baseline high carbohydrate run-in diet in men Secondary Aim 2: Determine whether fat oxidation during sleep is affected by NR supplementation during a ketogenic diet from the baseline run-in diet in men Exploratory Aims: Exploratory comparison of the above endpoints between men and women without MODY2. Exploratory comparison of the above diet-related endpoints between patients with MODY2 and those obtained during the Placebo period in other participants. Several exploratory measurements are planned to help comprehensively phenotype the effects of the diets and nicotinamide riboside supplementation and are intended to be hypothesis-generating. We will assess the following: Liver TG Liver NAD, ATP, and ATP synthesis rates Daily ketosis, insulin secretion, and protein utilization Rates of ketogenesis and lipolysis Physical activity and sleep assessment Body composition assessment Fasting and postprandial blood measurements of various metabolites, hormones, cytokines, and markers of inflammation. Microbiome composition Hunger and satiety before and after meals Eating rate Chronotype and sleep quality Usual food intake Endpoints: Primary: Mean change in sleeping energy expenditure between the ketogenic diet and the baseline run-in diet Mean difference in sleeping energy expenditure between NR and placebo during the ketogenic diet Secondary: Mean change in sleeping fat oxidation rate between the ketogenic diet and the baseline run-in diet Mean difference in fat oxidation rate between NR and placebo during the ketogenic diet Exploratory: 1H magnetic resonance spectroscopy 31P magnetic resonance spectroscopy 24hr urine ketones, C-peptide, nitrogen Stable isotope infusions of 13C beta-hydroxybutyrate and 2H glycerol Daily accelerometry and wireless EEG headband DXA scans Fasting and postprandial blood concentrations of various metabolites, hormones, cytokines and inflammatory markers Blood glucose variability and mean concentration as measured by Continuous Glucose Monitoring Daily fasting glucose and beta-hydroxybutyrate concentrations by finger-prick Microbiome composition Hunger and satiety visual analogue scores Meal duration Pittsburg sleep quality index, morningness-eveningness questionnaire, and subjective sleep visual analogue scores Usual food intake as measured by Food frequency questionnaire

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Overweight, Obesity
Keywords
Ketogenic Diet, Sleep, Energy Expenditure, Supplement, Calories

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Men with overweight or obesity
Arm Type
Experimental
Arm Description
To investigate whether NR supplementation augments the sleeping energy expenditure and fat oxidation rate during the ketogenic diet in men and women with overweight and obesity
Arm Title
MODY2 Patients
Arm Type
Experimental
Arm Description
To measure changes in sleeping energy expenditure and fat oxidation rate after transitioning from a baseline diet to an isocaloric ketogenic diet similar to our previous study in men
Arm Title
Women with overweight or obesity
Arm Type
Experimental
Arm Description
To investigate whether NR supplementation augments the sleeping energy expenditure and fat oxidation rate during the ketogenic diet in men and women with overweight and obesity
Intervention Type
Other
Intervention Name(s)
Standard Diet
Intervention Description
Consisting of 15% protein, 35% fat, and 50% carbohydrate, matching the macronutrient composition of a typical American diet
Intervention Type
Other
Intervention Name(s)
Ketogenic Diet
Intervention Description
Consisting of a macronutrient composition of 15% protein, 80% fat, and 5% carbohydrate
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Subjects without MODY2 will take either placebo or NR (1 g BID, 2 g per day total) supplements for 7 days during this Run-in phase
Intervention Type
Dietary Supplement
Intervention Name(s)
Nicotinamide Riboside
Intervention Description
Subjects without MODY2 will take either placebo or NR (1 g BID, 2 g per day total) supplements for 7 days during this Run-in phase
Primary Outcome Measure Information:
Title
Mean change in sleeping energy expenditure between the ketogenic diet and the baseline run-in diet
Description
Mean change in sleeping energy expenditure measured by room calorimetry from 2 days of standard run-in diet to 5 days of ketogenic diet
Time Frame
7 days
Title
Mean difference in sleeping energy expenditure between NR and placebo during the ketogenic diet
Description
Mean difference in sleeping energy expenditure measured by room calorimetry during 5 days of ketogenic diet with NR supplementation or placebo
Time Frame
5 days
Secondary Outcome Measure Information:
Title
Mean change in sleeping fat oxidation rate between the ketogenic diet and the baseline run-in diet
Description
Mean change in sleeping fat oxidation measured by room calorimetry from 2 days of standard run-in diet to 5 days of ketogenic diet
Time Frame
7 days
Title
Mean difference in fat oxidation rate between NR and placebo during the ketogenic diet
Description
Mean difference in sleeping fat oxidation measured by room calorimetry during 5 days of ketogenic diet with NR supplementation or placebo
Time Frame
5 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: Meet one of the following: Adult males aged 18-65 years Pre-menopausal adult females aged 18-50 years Adult males aged 18-65 years with diagnosed maturity-onset diabetes of the young type 2 (MODY2) or pre-menopausal adult females aged 18-50 years with diagnosed MODY2 Weight stable (< +/- 5 % body weight change over past 6 months) as determined by volunteer report Body mass index (BMI) >= 25 kg/M^2 Able to cycle at a moderate rate and intensity with a HR equal to or greater than 0.3(SqrRoot) (220-age-HRest)+HRest but not exceeding 0.4(SqrRoot) (220-age-HRest)+HRest with no signs of arrhythmia EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: Taking prescription medications or other drugs or supplements that may influence energy metabolism or nutrient digestion or absorption (including, but not limited to, diet/weight loss medication or other medications at the discretion of the PI and/or study team) Indicators of liver disease; combination of both albumin < 2.8 mg/mL and bilirubin > 3 mg/Ml Individuals with significant medical comorbidities (e.g., non-MODY2 diabetes, NYHA Class >II heart failure, or CKD Stage II or worse, or American Society of Anesthesiologists Physical Status Class 3 or above) Individuals taking prescription medications to treat hypertension in participants without MODY2 Participating in a regular exercise program (> 2h/week of vigorous activity) as determined by volunteer report Positive pregnancy test (females only) Hematocrit < 40% (men only) Hematocrit <37% (women only) Caffeine consumption > 300 mg/day as determined by volunteer report Alcohol consumption > 3 drinks per day for men or > 2 drinks per day for women as determined by volunteer report Regular use of tobacco (smoking or chewing), e-cigarettes (a.k.a. vapes), nicotine patches, or illicit drugs over past 6 months as determined by volunteer report. Subjects may also be excluded based on a urine drug test. Psychological conditions as determined by volunteer report such as (but not limited to) eating disorders, depression, bipolar disorders, that would be incompatible with safe and successful participation in this study, as determined by investigators Volunteers with strict dietary concerns (e.g. vegetarian or kosher diet, food allergies) or a reported dislike of a significant fraction of the study foods Unwilling or unable to comply with or perform all study procedures (e.g. cycling or activities of daily living), or unavailability for the duration of the study, as determined by participant or investigator discretion Unwilling or unable to adhere to Lifestyle Considerations throughout study duration, as determined by participant or investigator discretion Volunteers unwilling or unable to give informed consent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nan Zhai, C.R.N.P.
Phone
(301) 827-3324
Email
nan.zhai@nih.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Kevin Hall, Ph.D.
Phone
(301) 402-8248
Email
kevinh@niddk.nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kevin Hall, Ph.D.
Organizational Affiliation
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
NIH Clinical Center Office of Patient Recruitment (OPR)
Phone
800-411-1222
Ext
TTY dial 711
Email
ccopr@nih.gov

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
.demographics, anthropometrics, indirect calorimetry data, circulating metabolites and hormones
IPD Sharing Time Frame
Upon publication in peer reviewed journal
IPD Sharing Access Criteria
Open
Citations:
PubMed Identifier
27385608
Citation
Hall KD, Chen KY, Guo J, Lam YY, Leibel RL, Mayer LE, Reitman ML, Rosenbaum M, Smith SR, Walsh BT, Ravussin E. Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men. Am J Clin Nutr. 2016 Aug;104(2):324-33. doi: 10.3945/ajcn.116.133561. Epub 2016 Jul 6.
Results Reference
background
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_001690-DK.html
Description
NIH Clinical Center Detailed Web Page

Learn more about this trial

Effect of Nicotinamide Riboside on Ketosis, Fat Oxidation & Metabolic Rate

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