NCT06044935 · National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Effect of Nicotinamide Riboside on Ketosis, Fat Oxidation & Metabolic Rate
What this study is about
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.
View original scientific description
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. ...
Interventions
OTHER
Standard Diet
Consisting of 15% protein, 35% fat, and 50% carbohydrate, matching the macronutrient composition of a typical American diet
OTHER
Ketogenic Diet
Consisting of a macronutrient composition of 15% protein, 80% fat, and 5% carbohydrate
DIETARY_SUPPLEMENT
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
DIETARY_SUPPLEMENT
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 measures
Mean change in sleeping energy expenditure between the ketogenic diet and the baseline run-in diet
Time frame: 7 days
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
Time frame: 5 days
Mean difference in sleeping energy expenditure measured by room calorimetry during 5 days of ketogenic diet with NR supplementation or placebo
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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 (of \>=18.5 kg/m\^2 for patients with MODY2)
- 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:
- 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 (only for people who can get pregnant)
- 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
- Participants with a measured Resting Energy Expenditure (REE) more than 30% above or below the predicted REE based on Mifflin St Jeor equation
Where
- Bethesda, Maryland
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 22, 2026 · Source of record for eligibility and locations