ObesityPhase 2NCT00846040
Reduced Carbohydrate Versus Fat in Obese Subjects
A Phase 2 study testing Reduced fat diet, Reduced carbohydrate diet and Drug: f-18 fallypride in people with Obesity, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Popular weight loss strategies often involve reducing an individual's consumption of carbohydrates or fat. However, no controlled study has been carried out to evaluate the effects of reducing carbohydrate versus fat consumption while keeping the other nutrients at standard levels to maintain an individual's weight. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Obesity
- What is being tested?
- Reduced fat diet, Reduced carbohydrate diet and Drug: f-18 fallypride
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Feb 2009to 20 Oct 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 18-45 years, male or female
- Body mass less than 350 lbs. (max. weight dictated by table limit for functional magnetic resonance imaging (fMRI) scanner) when acquisition of large bore fMRI is complete, max. wt. limit will increase to 400 lbs.
- Weight stable (less than plus or minus 5 kg over past 6 months)
- Body mass index greater than or equal to 30.0 kg/m(2)
- Premenopausal (women only)
- Healthy, as determined by medical history and laboratory tests
Show all 14Show fewer
- Able to complete daily bouts of walking at a moderate rate
- Written informed consent
- Age 18-45 years, male or female
- 18.5 kg/m(2) less than BMI less than 25.0 kg/m(2)
- Weight stable (less than plus or minus 5 kg over past 6 months)
- Premenopausal (women only)
- Healthy, as determined by medical history and laboratory tests
- Written informed consent
Who cannot join
- Body mass greater than 350 lbs. (max. weight dictated by table limit for fMRI scanner) when acquisition of large bore fMRI is complete, max. wt. limit will increase to 400 lbs.
- BMI less than 30.0 kg/m(2)
- Evidence of metabolic or cardiovascular disease, or disease that may influence metabolism (e.g. cancer, diabetes, thyroid disease)
- Taking any prescription medication (except birth control) or other drug that may influence metabolism (e.g. diet/weight-loss medication)
- Hematocrit less than 34% (women only)
- Hematocrit less than 40% (men only)
Show all 36Show fewer
- Pregnancy, lactation (women only)
- Allergy to lidocaine or ethanol
- Participating in a regular exercise program (greater than 2h/week of vigorous activity)
- Caffeine consumption greater than 150 mg/day (will be clamped at baseline intake during study)
- Regular use of alcohol (greater than 2 drinks per day), tobacco (smoking or chewing), amphetamines, cocaine, heroin, or marijuana over past 6 months
- Past or present history of eating disorder (including binge eating) or psychiatric disease
- Volunteers with strict dietary concerns (e.g. vegetarian or kosher diet, multiple food allergies)
- Are claustrophobic to a degree that they would feel uncomfortable in the MRI machine.
- Having any metal in their body (for example, pacemakers, metallic prostheses such as cochlear implants or heart valves, shrapnel fragments, etc.).
- Left-handedness
- Non-native English speakers
- Volunteers unwilling or unable to give informed consent
- Control Subjects
- BMI less than 18.5 or greater than 25.0 kg/m(2)
- Evidence of metabolic or cardiovascular disease, or disease that may influence metabolism (e.g. cancer or diabetes)
- Taking any prescription medication (except birth control) or other drug that may influence metabolism (e.g. diet/weight-loss medication)
- Hyperlipidemia (fasting plasma triglyceride concentration greater than 150 mg/dl)
- Hematocrit less than 34% (women only)
- Hematocrit less than 40% (men only)
- Pregnancy, lactation (women only)
- Participating in a regular exercise program (greater than 2h/week of vigorous activity)
- Caffeine consumption greater than 150 mg/day
- Regular use of alcohol (greater than 2 drinks per day), tobacco (smoking or chewing), amphetamines, cocaine, heroin, or marijuana over the past 6 months
- Past or present history of eating disorder (including binge eating) or psychiatric disease
- Volunteers with strict dietary concerns (e.g vegetarian or kosher diet, multiple food allergies)
- Are claustrophobic to a degree that they would feel uncomfortable in the MRI machine.
- Having any metal in their body (for example, pacemakers, metallic prostheses such as cochlear implants or heart valves, shrapnel fragments, etc.).
- Left-handedness
- Non-native English speakers
- Volunteers unwilling or unable to give informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Selective Reduction of Dietary Carbohydrate Versus Fat: Effects on Metabolism, Endocrine Physiology, Brain Activity and Reward Circuitry
Popular weight loss strategies often involve reducing an individual's consumption of carbohydrates or fat. However, no controlled study has been carried out to evaluate the effects of reducing carbohydrate versus fat consumption while keeping the other nutrients at standard levels to maintain an individual's weight. Researchers are interested in investigating how different restrictions of carbohydrates or fats affect the many processes involved in weight loss, including brain activity and blood and brain chemical composition.
Read the detailed description
Popular weight loss strategies often prescribe a targeted reduction of dietary carbohydrate or fat. But surprisingly, no controlled human feeding study has ever investigated the effects of a selective reduction of dietary carbohydrate versus fat while keeping the other dietary macronutrients at their baseline weight-maintenance values. The present study was designed to address this knowledge gap and improve our understanding of how selective reduction of dietary fat versus carbohydrate may differentially impact the many feedback control processes that act to resist weight loss.
Objectives:
- To determine the comparative effects of two controlled fat- or carbohydrate-restricted diets and an outpatient weight loss program on blood and brain chemical composition, weight loss (fat and lean body mass), and regional brain activity in lean and obese individuals.
Eligibility:
- Healthy individuals between 18 and 45 years of age who are either lean (body mass index between 18.5 kg/m(2) and 25 kg/m(2)) or obese (body mass index above 30.0 kg/m(2), weight less than 350 pounds) and are right-handed.
Design:
- Lean participants: Participants will be screened with a medical history, physical examination, blood and urine tests, and weight maintenance observations (food diaries and physical activity monitors). For the scanning visit, participants will receive balanced meals from the National Institutes of Health to consume for 2 days before the visit. During the scanning visit, participants will continue to eat the weight maintenance diet, complete questionnaires, and have a series of imaging studies (including positron emission tomography and magnetic resonance imaging tests) to evaluate brain response to food and other stimuli.
- Obese participants: Participants will be screened with a medical history, physical examination, blood and urine tests, and weight maintenance observations (food diaries and physical activity monitors). During the first inpatient visit, obese participants will eat a weight-maintenance diet for 5 days to establish baseline measurements. After several days of eating a weight-maintenance diet, 20 obese adult volunteers (BMI above 30 kg/m2) will be admitted to the metabolic clinical research unit (MCRU) and, after 5 additional days of the baseline diet, their diets will be modified to result in either 85% reduction of the baseline dietary fat or a 60% reduction of the baseline dietary carbohydrate for the next 6 days. These diet modifications produce an equivalent caloric reduction. The primary outcome measurements will be changes of metabolism, brain reward circuitry and regional brain activity in response to food stimuli measured during the baseline and reduced calorie diet phases. Immediately following each controlled diet, we will measure 3 days of ad-libitum food intake using a computerized vending machine system. The subjects will return to the MCRU after a 2-10 week washout period to receive the opposite reduced calorie diet. Twenty control subjects with normal body weight (BMI between 18.5 - 25 kg/m2) will have measurements of brain reward circuitry and regional brain activity in response to food stimuli while on a balanced, weight-maintenance diet. Immediately following the second in-patient visit, all of the obese subjects will be assigned to a 12 week out-patient weight loss program with the goal of achieving at least 5% weight loss. We will investigate the relationship between short-term fat imbalances measured during the in-patient phases, and the body weight and fat changes during the weight loss program. We will evaluate the effects of weight loss on metabolism, brain reward circuitry, and regional brain activity in response to food stimuli. Finally, if the subjects are available for long-term follow-up, then we will investigate their metabolic phenotype, brain reward circuitry, and regional brain activity in response to food stimuli yearly over the subsequent 5 years following the weight loss intervention. This study will result in an improved understanding of the physiological mechanisms that sense and respond to negative energy balance acutely, after several weeks, and after several years, and may eventually lead to increased long-term success of obesity treatment.
- Conditions
- Obesity
- Being tested
- Reduced fat diet, Reduced carbohydrate diet, Drug: f-18 fallypride, fMRI, PET
- Keywords
- Obesity, Weight Loss, Carbohydrate, Fat, Macronutrient Balance, Healthy Volunteer
- Medical subject headings
- Obesity, Weight Loss, Platelet Glycoprotein IV Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reduced fat dietOther
RF (selective reduction of 85% of baseline fat calories per day)
Reduced carbohydrate dietOther
RC (selective reduction of 60% of baseline carbohydrate calories per day)
Drug: f-18 fallyprideDrug
Dopamine D2 receptor availability is measured by positron emission tomography (PET) using the positron emitting compound [18F] fallypride which binds competitively with dopamine to the D2 receptor.
fMRIDevice
Also called Functional MRI
Functional MRI (fMRI) will be used to measure the effects of diet and weight loss on regional brain activity
PETDevice
Also called Positron emission tomography
Positron emission tomography (PET) will be used to assess whether To assess whether brain activity and reward pathways are altered
| Study group | Role | What they receive |
|---|---|---|
| Obese RF then RC | Experimental | Obese adult volunteers (BMI above 30 kg/m2) randomized to receive an 85% reduction of baseline dietary fat (RF) for 2 weeks. After a washout period of 2 weeks, they then received a 60% reduction of baseline dietary carbohydrate (RC) for 2 weeks Receives: Other: Reduced fat diet; Other: Reduced carbohydrate diet; Drug: Drug: f-18 fallypride; Device: fMRI; Device: PET |
| Obese RC then RF | Experimental | Obese adult volunteers (BMI above 30 kg/m2) randomized to receive a 60% reduction of baseline dietary carbohydrate (RC) for 2 weeks. After a washout period of 2 weeks, they then received an 85% reduction of baseline dietary fat (RF) for 2 weeks. Receives: Other: Reduced fat diet; Other: Reduced carbohydrate diet; Drug: Drug: f-18 fallypride; Device: fMRI; Device: PET |
| Lean Control | Active comparator | Lean adult volunteers (BMI below 30kg/m2) placed on a weight-maintenance diet using a standard diet composition of 50% carbohydrate, 35% fat, and 15% protein on an out-patient basis Receives: Drug: Drug: f-18 fallypride; Device: fMRI; Device: PET |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Respiratory Quotient (RQ)
Respiratory quotient was calculated as the ratio of carbon dioxide production to oxygen consumption as measured in a metabolic chamber for at least 23 continuous hours on days 2 and 5 of the baseline diet and days 1, 4, and 6 of the reduced-energy diets.
Measured: Baseline and day 14
Secondary outcomes (5)
Change in 24 Hour Energy Expenditure
24 hour energy expenditure was measured in a respiratory chamber.
Measured: Baseline and 14 days
Change in Cumulative Fat Imbalance
Measured as the difference between dietary fat intake and fat oxidation by the body as measured in the respiratory chamber
Measured: Baseline and 14 days
Caudate Dopamine D2-like Receptor Binding Potential (D2BP)
The time-activity curves for [18F]fallypride tracer concentration in the ROIs were measured by PET and kinetic parameters were fit to a four compartment mathematical model (with the cerebellum used as the reference tissue). D2BP was expressed as the dimensionless ratio of rate constants quantifying binding and unbinding of tracer in the regions of interest.
Measured: Day 2 of in-patient admission
Putamen Dopamine D2-like Receptor Binding Potential (D2BP)
The time-activity curves for [18F]fallypride tracer concentration in the ROIs were measured by PET and kinetic parameters were fit to a four compartment mathematical model (with the cerebellum used as the reference tissue). D2BP was expressed as the dimensionless ratio of rate constants quantifying binding and unbinding of tracer in the regions of interest.
Measured: Day 2 of in-patient admission
Accumbens Dopamine D2-like Receptor Binding Potential (D2BP)
The time-activity curves for [18F]fallypride tracer concentration in the ROIs were measured by PET and kinetic parameters were fit to a four compartment mathematical model (with the cerebellum used as the reference tissue). D2BP was expressed as the dimensionless ratio of rate constants quantifying binding and unbinding of tracer in the regions of interest.
Measured: Day 2 of in-patient admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2009 (estimated)
- Study start13 Feb 2009
- Primary completion24 Feb 2014
- Study completion20 Oct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kevin Hall, Ph.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00846040
- Sponsor's protocol ID
- 090081
- Other IDs
- 09-DK-0081
- Status last verified
- 22 Jan 2020
- First submitted
- 14 Feb 2009
- Last updated
- 15 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Publications
Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity. JAMA. 1999 Oct 27;282(16):1523-9. doi: 10.1001/jama.282.16.1523.
PubMed 10546691Allison DB, Zannolli R, Narayan KM. The direct health care costs of obesity in the United States. Am J Public Health. 1999 Aug;89(8):1194-9. doi: 10.2105/ajph.89.8.1194.
PubMed 10432905Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, Williams T, Williams M, Gracely EJ, Stern L. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med. 2003 May 22;348(21):2074-81. doi: 10.1056/NEJMoa022637.
PubMed 12761364Hall KD, Bemis T, Brychta R, Chen KY, Courville A, Crayner EJ, Goodwin S, Guo J, Howard L, Knuth ND, Miller BV 3rd, Prado CM, Siervo M, Skarulis MC, Walter M, Walter PJ, Yannai L. Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity. Cell Metab. 2015 Sep 1;22(3):427-36. doi: 10.1016/j.cmet.2015.07.021. Epub 2015 Aug 13.
PubMed 26278052Guo J, Simmons WK, Herscovitch P, Martin A, Hall KD. Striatal dopamine D2-like receptor correlation patterns with human obesity and opportunistic eating behavior. Mol Psychiatry. 2014 Oct;19(10):1078-84. doi: 10.1038/mp.2014.102. Epub 2014 Sep 9.
PubMed 25199919Simmons WK, Rapuano KM, Ingeholm JE, Avery J, Kallman S, Hall KD, Martin A. The ventral pallidum and orbitofrontal cortex support food pleasantness inferences. Brain Struct Funct. 2014 Mar;219(2):473-83. doi: 10.1007/s00429-013-0511-0. Epub 2013 Feb 9.
PubMed 23397317Simmons WK, Rapuano KM, Kallman SJ, Ingeholm JE, Miller B, Gotts SJ, Avery JA, Hall KD, Martin A. Category-specific integration of homeostatic signals in caudal but not rostral human insula. Nat Neurosci. 2013 Nov;16(11):1551-2. doi: 10.1038/nn.3535. Epub 2013 Sep 29.
PubMed 24077565Darcey VL, Guo J, Courville AB, Gallagher I, Avery JA, Simmons WK, Ingeholm JE, Herscovitch P, Martin A, Hall KD. Dietary fat restriction affects brain reward regions in a randomized crossover trial. JCI Insight. 2023 Jun 22;8(12):e169759. doi: 10.1172/jci.insight.169759.
PubMed 37345661
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Selective Reduction of Dietary Carbohydrate Versus Fat: Effects on Metabolism, Endocrine Physiology, Brain Activity and Reward Circuitry
- ClinicalTrials.gov ID
- NCT00846040
- Acronym / sponsor ID
- 090081
- Conditions
- Obesity
- Keywords
- Obesity, Weight Loss, Carbohydrate, Fat, Macronutrient Balance, Healthy Volunteer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 13 Feb 2009
- Primary completion
- 24 Feb 2014 (actual)
- Study completion
- 20 Oct 2014 (actual)
- First posted
- 18 Feb 2009 (estimated)
- Results
- Posted 24 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Popular weight loss strategies often involve reducing an individual's consumption of carbohydrates or fat. However, no controlled study has been carried out to evaluate the effects of reducing carbohydrate versus fat consumption while keeping the other nutrients at standard levels to maintain an individual's weight. Researchers are interested in investigating how different restrictions of carbohydrates or fats affect the many processes involved in weight loss, including brain activity and blood and brain chemical composition.
Detailed description
Popular weight loss strategies often prescribe a targeted reduction of dietary carbohydrate or fat. But surprisingly, no controlled human feeding study has ever investigated the effects of a selective reduction of dietary carbohydrate versus fat while keeping the other dietary macronutrients at their baseline weight-maintenance values. The present study was designed to address this knowledge gap and improve our understanding of how selective reduction of dietary fat versus carbohydrate may differentially impact the many feedback control processes that act to resist weight loss.
Objectives:
- To determine the comparative effects of two controlled fat- or carbohydrate-restricted diets and an outpatient weight loss program on blood and brain chemical composition, weight loss (fat and lean body mass), and regional brain activity in lean and obese individuals.
Eligibility:
- Healthy individuals between 18 and 45 years of age who are either lean (body mass index between 18.5 kg/m(2) and 25 kg/m(2)) or obese (body mass index above 30.0 kg/m(2), weight less than 350 pounds) and are right-handed.
Design:
- Lean participants: Participants will be screened with a medical history, physical examination, blood and urine tests, and weight maintenance observations (food diaries and physical activity monitors). For the scanning visit, participants will receive balanced meals from the National Institutes of Health to consume for 2 days before the visit. During the scanning visit, participants will continue to eat the weight maintenance diet, complete questionnaires, and have a series of imaging studies (including positron emission tomography and magnetic resonance imaging tests) to evaluate brain response to food and other stimuli.
- Obese participants: Participants will be screened with a medical history, physical examination, blood and urine tests, and weight maintenance observations (food diaries and physical activity monitors). During the first inpatient visit, obese participants will eat a weight-maintenance diet for 5 days to establish baseline measurements. After several days of eating a weight-maintenance diet, 20 obese adult volunteers (BMI above 30 kg/m2) will be admitted to the metabolic clinical research unit (MCRU) and, after 5 additional days of the baseline diet, their diets will be modified to result in either 85% reduction of the baseline dietary fat or a 60% reduction of the baseline dietary carbohydrate for the next 6 days. These diet modifications produce an equivalent caloric reduction. The primary outcome measurements will be changes of metabolism, brain reward circuitry and regional brain activity in response to food stimuli measured during the baseline and reduced calorie diet phases. Immediately following each controlled diet, we will measure 3 days of ad-libitum food intake using a computerized vending machine system. The subjects will return to the MCRU after a 2-10 week washout period to receive the opposite reduced calorie diet. Twenty control subjects with normal body weight (BMI between 18.5 - 25 kg/m2) will have measurements of brain reward circuitry and regional brain activity in response to food stimuli while on a balanced, weight-maintenance diet. Immediately following the second in-patient visit, all of the obese subjects will be assigned to a 12 week out-patient weight loss program with the goal of achieving at least 5% weight loss. We will investigate the relationship between short-term fat imbalances measured during the in-patient phases, and the body weight and fat changes during the weight loss program. We will evaluate the effects of weight loss on metabolism, brain reward circuitry, and regional brain activity in response to food stimuli. Finally, if the subjects are available for long-term follow-up, then we will investigate their metabolic phenotype, brain reward circuitry, and regional brain activity in response to food stimuli yearly over the subsequent 5 years following the weight loss intervention. This study will result in an improved understanding of the physiological mechanisms that sense and respond to negative energy balance acutely, after several weeks, and after several years, and may eventually lead to increased long-term success of obesity treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Obese RF then RC | Experimental | Other: Reduced fat diet, Other: Reduced carbohydrate diet, Drug: Drug: f-18 fallypride, Device: fMRI, Device: PETObese adult volunteers (BMI above 30 kg/m2) randomized to receive an 85% reduction of baseline dietary fat (RF) for 2 weeks. After a washout period of 2 weeks, they then received a 60% reduction of baseline dietary carbohydrate (RC) for 2 weeks |
| Obese RC then RF | Experimental | Other: Reduced fat diet, Other: Reduced carbohydrate diet, Drug: Drug: f-18 fallypride, Device: fMRI, Device: PETObese adult volunteers (BMI above 30 kg/m2) randomized to receive a 60% reduction of baseline dietary carbohydrate (RC) for 2 weeks. After a washout period of 2 weeks, they then received an 85% reduction of baseline dietary fat (RF) for 2 weeks. |
| Lean Control | Active comparator | Drug: Drug: f-18 fallypride, Device: fMRI, Device: PETLean adult volunteers (BMI below 30kg/m2) placed on a weight-maintenance diet using a standard diet composition of 50% carbohydrate, 35% fat, and 15% protein on an out-patient basis |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Age 18-45 years, male or female
- Body mass less than 350 lbs. (max. weight dictated by table limit for functional magnetic resonance imaging (fMRI) scanner) when acquisition of large bore fMRI is complete, max. wt. limit will increase to 400 lbs.
- Weight stable (less than plus or minus 5 kg over past 6 months)
- Body mass index greater than or equal to 30.0 kg/m(2)
- Premenopausal (women only)
Key exclusion criteria (36 listed)
- Body mass greater than 350 lbs. (max. weight dictated by table limit for fMRI scanner) when acquisition of large bore fMRI is complete, max. wt. limit will increase to 400 lbs.
- BMI less than 30.0 kg/m(2)
- Evidence of metabolic or cardiovascular disease, or disease that may influence metabolism (e.g. cancer, diabetes, thyroid disease)
- Taking any prescription medication (except birth control) or other drug that may influence metabolism (e.g. diet/weight-loss medication)
- Hematocrit less than 34% (women only)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Reduced fat dietRF (selective reduction of 85% of baseline fat calories per day) | Other | Obese RC then RF, Obese RF then RC |
| Reduced carbohydrate dietRC (selective reduction of 60% of baseline carbohydrate calories per day) | Other | Obese RC then RF, Obese RF then RC |
| Drug: f-18 fallyprideDopamine D2 receptor availability is measured by positron emission tomography (PET) using the positron emitting compound [18F] fallypride which binds competitively with dopamine to the D2 receptor. | Drug | Lean Control, Obese RC then RF, Obese RF then RC |
| fMRIAlso: Functional MRIFunctional MRI (fMRI) will be used to measure the effects of diet and weight loss on regional brain activity | Device | Lean Control, Obese RC then RF, Obese RF then RC |
| PETAlso: Positron emission tomographyPositron emission tomography (PET) will be used to assess whether To assess whether brain activity and reward pathways are altered | Device | Lean Control, Obese RC then RF, Obese RF then RC |
Primary outcome
Change in Respiratory Quotient (RQ)
Time frame: Baseline and day 14
Respiratory quotient was calculated as the ratio of carbon dioxide production to oxygen consumption as measured in a metabolic chamber for at least 23 continuous hours on days 2 and 5 of the baseline diet and days 1, 4, and 6 of the reduced-energy diets.
5 secondary outcomes
Change in 24 Hour Energy Expenditure
Time frame: Baseline and 14 days
Change in Cumulative Fat Imbalance
Time frame: Baseline and 14 days
Caudate Dopamine D2-like Receptor Binding Potential (D2BP)
Time frame: Day 2 of in-patient admission
Putamen Dopamine D2-like Receptor Binding Potential (D2BP)
Time frame: Day 2 of in-patient admission
Accumbens Dopamine D2-like Receptor Binding Potential (D2BP)
Time frame: Day 2 of in-patient admission
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10546691Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity. JAMA. 1999 Oct 27;282(16):1523-9. doi: 10.1001/jama.282.16.1523.
- Background: PubMed 10432905Allison DB, Zannolli R, Narayan KM. The direct health care costs of obesity in the United States. Am J Public Health. 1999 Aug;89(8):1194-9. doi: 10.2105/ajph.89.8.1194.
- Background: PubMed 12761364Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, Williams T, Williams M, Gracely EJ, Stern L. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med. 2003 May 22;348(21):2074-81. doi: 10.1056/NEJMoa022637.
- Results publication: PubMed 26278052Hall KD, Bemis T, Brychta R, Chen KY, Courville A, Crayner EJ, Goodwin S, Guo J, Howard L, Knuth ND, Miller BV 3rd, Prado CM, Siervo M, Skarulis MC, Walter M, Walter PJ, Yannai L. Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity. Cell Metab. 2015 Sep 1;22(3):427-36. doi: 10.1016/j.cmet.2015.07.021. Epub 2015 Aug 13.
- Results publication: PubMed 25199919Guo J, Simmons WK, Herscovitch P, Martin A, Hall KD. Striatal dopamine D2-like receptor correlation patterns with human obesity and opportunistic eating behavior. Mol Psychiatry. 2014 Oct;19(10):1078-84. doi: 10.1038/mp.2014.102. Epub 2014 Sep 9.
- Results publication: PubMed 23397317Simmons WK, Rapuano KM, Ingeholm JE, Avery J, Kallman S, Hall KD, Martin A. The ventral pallidum and orbitofrontal cortex support food pleasantness inferences. Brain Struct Funct. 2014 Mar;219(2):473-83. doi: 10.1007/s00429-013-0511-0. Epub 2013 Feb 9.
- Results publication: PubMed 24077565Simmons WK, Rapuano KM, Kallman SJ, Ingeholm JE, Miller B, Gotts SJ, Avery JA, Hall KD, Martin A. Category-specific integration of homeostatic signals in caudal but not rostral human insula. Nat Neurosci. 2013 Nov;16(11):1551-2. doi: 10.1038/nn.3535. Epub 2013 Sep 29.
- Derived from this study: PubMed 37345661Darcey VL, Guo J, Courville AB, Gallagher I, Avery JA, Simmons WK, Ingeholm JE, Herscovitch P, Martin A, Hall KD. Dietary fat restriction affects brain reward regions in a randomized crossover trial. JCI Insight. 2023 Jun 22;8(12):e169759. doi: 10.1172/jci.insight.169759.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Effect of Probiotics on Insulin Sensitivity in Overweight and Obese Pregnancy
Obesity & Overweight, Gestational Diabetes Mellitus (GDM)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin Hall, Ph.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Reduced fat diet, Reduced carbohydrate diet and Drug: f-18 fallypride in people with Obesity, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Respiratory Quotient (RQ) (time frame: Baseline and day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00846040, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2021.