Recruiting

Nicotinamide Riboside

Sponsor:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Code:

NCT06044935

Conditions

Overweight

Obesity

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Standard Diet

Ketogenic Diet

Placebo

Nicotinamide Riboside

Study Details

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.

...

Conditions

Overweight

Obesity

Study ID

NCT06044935

Start date

Jan 8, 2024

Status verified date

Sep 2, 2026

Completion date

Jan 31, 2028

Anticipated

Primary completion date

Jan 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

  • INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Meet one of the following:

1. Adult males aged 18-65 years
2. Pre-menopausal adult females aged 18-50 years
3. 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
2. Weight stable (< +/- 5 % body weight change over past 6 months) as determined by volunteer report
3. Body mass index (BMI) >= 25 kg/m\^2 (of >=18.5 kg/m\^2 for patients with MODY2)
4. Able to cycle at a moderate rate and intensity with a HR equal to or greater than 0.3x(220-age-HRrest)+HRrest but not exceeding 0.4x(220-age-HRrest)+HRrest with no signs of arrhythmia

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. 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)
2. Indicators of liver disease; combination of both albumin < 2.8 mg/mL and bilirubin > 3 mg/mL
3. 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)
4. Individuals taking prescription medications to treat hypertension in participants without MODY2
5. Participating in a regular exercise program (> 2h/week of vigorous activity) as determined by volunteer report
6. Positive pregnancy test (only for people who can get pregnant)
7. Hematocrit < 40% (men only)
8. Hematocrit <37% (women only)
9. Caffeine consumption > 300 mg/day as determined by volunteer report
10. Alcohol consumption > 3 drinks per day for men or > 2 drinks per day for women as determined by volunteer report
11. 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.
12. 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
13. 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
14. 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
15. Unwilling or unable to adhere to Lifestyle Considerations throughout study duration, as determined by participant or investigator discretion
16. Volunteers unwilling or unable to give informed consent
17. Participants with a measured Resting Energy Expenditure (REE) more than 30% above or below the predicted REE based on Mifflin St Jeor equation

Study Design

Enrollment

100 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Men with overweight or obesity

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

experimental: MODY2 Patients

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

experimental: Women with overweight or obesity

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

Interventions

Standard Diet

Consisting of 15% protein, 35% fat, and 50% carbohydrate, matching the macronutrient composition of a typical American diet

Ketogenic Diet

Consisting of a macronutrient composition of 15% protein, 80% fat, and 5% carbohydrate

Placebo

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

Nicotinamide Riboside

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

  • Mean change in sleeping energy expenditure between the ketogenic diet and the baseline run-in diet [ Time Frame: 7 days ]
  • Mean difference in sleeping energy expenditure between NR and placebo during the ketogenic diet [ Time Frame: 5 days ]

Central Contacts and Locations

Central contacts

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

NIH Clinical Center Office of Patient Recruitment (OPR)

800-411-1222ccopr@nih.gov

More Information

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Last update posted

Sep 4, 2026

Last verified

Sep 2, 2026

Keywords

  • Ketogenic Diet
  • Sleep
  • Energy Expenditure
  • Supplement
  • Calories

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) on 2026-09-04.