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Brain Dopamine Function in Human Obesity

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ClinicalTrials.gov Identifier: NCT03648892
Recruitment Status : Recruiting
First Posted : August 28, 2018
Last Update Posted : October 8, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )

Brief Summary:

Background:

Dopamine is a natural chemical in the brain that may influence eating behavior and physical activity. Researchers want to measure the brain s dopamine activity and understand how it differs in people with obesity.

Objective:

To better understand how brain function, particularly dopamine activity, relates to body weight and eating behavior.

Individuals may be able to participate if they:

Have a BMI of at least 18.5 kg/m2

Are weight-stable and generally healthy

Are between ages 18-45 years

Have normal blood pressure

Are not using illegal drugs (based on urine drug screen)

Are not following a special diet

Do not have metal implants

Design:

Participants will be screened with:

  • Medical history
  • Physical exam
  • Questionnaires and an interview to see if it is safe to have a PET/MRI scan
  • Fasting blood and urine tests
  • Participants will eat a special diet given to them for the 5 days before their inpatient visit.

Participants will have a 5-day inpatient visit. Some days include blood and urine tests. Each day includes surveys and tests to measure habits and likes/dis-likes. A sample schedule may be:

Day 1: Participants will wear a monitor that uses a needle below the skin to measure glucose. Their body fat will be measured with low-dose x-rays

Day 2: Participants will have a PET scan. They will lie on a table that slides in and out of a donut-shaped scanner. They will be injected with a small amount of a radioactive substance and wear a cap on their head.

Day 3: Participants will have an MRI. They will lie on a table that slides in and out of a scanner.

Day 4: Participants will have another PET scan. This time, they will drink a milk shake during a break from the scanner. Then, they will go back inside the scanner for the end of their scan.

Day 5: Participants will wear a hood for up to 40 minutes to measure their breathing. They will also drink special water and collect samples of their urine to measure the rate they burn energy.

For 12 months after the visit, participants will track their weight and physical activity daily using a special scale and activity monitor. A few times over the year, the study team will send participants special activity monitors to use for 7 days at a time.

Participants will have an in-person 1-day follow-up visit. This includes most tests except for PET scanning.


Condition or disease Intervention/treatment Phase
Obesity Healthy Volunteers Overweight Drug: [c11] raclopride Drug: [18F]fallypride Early Phase 1

Detailed Description:
Evidence from neuroimaging studies indicates that aberrant functionality in brain regions that support reward processing and habit formation may be related to an individual's eating behavior and obesity propensity. In particular, our previous research found that increased dopamine D2 receptor binding potential (D2BP) in the dorsal and lateral striatum was positively related to opportunistic eating behaviors, body fat, and body mass index (BMI). However, our findings were contrary to highly-cited previous reports of D2BP correlating with BMI in the opposite direction. The primary aim of this study is to elucidate the reasons for the conflicting results that used somewhat different methodologies. Specifically, our previous study used positron emission tomography (PET) to measure D2BP using the dopamine D2 receptor antagonist radioligand [18F]fallypride following a period of dietary stabilization and 3 hours after a standardized breakfast. Reports finding correlations between D2BP and BMI in the opposite direction have typically investigated subjects with higher BMI using the D2 receptor antagonist radioligand [11C]raclopride. Furthermore, previous studies were typically conducted in the fasted state, but the subjects' prior food intake was not well-controlled. The present study will attempt to resolve the controversy by measuring D2BP using both [18F]fallypride and [11C]raclopride in 39 adults, 13 within each of three BMI strata to represent a large BMI range, under controlled overnight fasting conditions following a period of dietary stabilization. The primary aims are to estimate the mathematical relationship between striatal D2BP and BMI and determine the within-subject correlations of D2BP derived from [18F]fallypride and [11C]raclopride.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Brain Dopamine Function in Human Obesity
Actual Study Start Date : September 21, 2018
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Dopamine

Arm Intervention/treatment
1
Healthy Volunteers with a BMI greater than or equal to 18.5 kg/m^2 and less than 25 kg/m^2
Drug: [c11] raclopride
The present study will attempt to resolve the controversy by measuring D2BP using both [18F]fallypride and [11C]raclopride in 39 adults, 13 within each of three BMI strata to represent a large BMI range, under controlled overnight fasting conditions following a period of dietary stabilization. The primary aims are to estimate the mathematical relationship between striatal D2BP and BMI and determine the within-subject correlations of D2BP derived from [18F]fallypride and [11C]raclopride.

Drug: [18F]fallypride
The present study will attempt to resolve the controversy by measuring D2BP using both [18F]fallypride and [11C]raclopride in 39 adults, 13 within each of three BMI strata to represent a large BMI range, under controlled overnight fasting conditions following a period of dietary stabilization. The primary aims are to estimate the mathematical relationship between striatal D2BP and BMI and determine the within-subject correlations of D2BP derived from [18F]fallypride and [11C]raclopride.

2
Healthy Volunteers with a BMI greater than or equal to 25 kg/m^2 and less than 35 kg/m^2
Drug: [c11] raclopride
The present study will attempt to resolve the controversy by measuring D2BP using both [18F]fallypride and [11C]raclopride in 39 adults, 13 within each of three BMI strata to represent a large BMI range, under controlled overnight fasting conditions following a period of dietary stabilization. The primary aims are to estimate the mathematical relationship between striatal D2BP and BMI and determine the within-subject correlations of D2BP derived from [18F]fallypride and [11C]raclopride.

Drug: [18F]fallypride
The present study will attempt to resolve the controversy by measuring D2BP using both [18F]fallypride and [11C]raclopride in 39 adults, 13 within each of three BMI strata to represent a large BMI range, under controlled overnight fasting conditions following a period of dietary stabilization. The primary aims are to estimate the mathematical relationship between striatal D2BP and BMI and determine the within-subject correlations of D2BP derived from [18F]fallypride and [11C]raclopride.

3
Healthy Volunteers with a BMI greater than or equal to 35 kg/m^2
Drug: [c11] raclopride
The present study will attempt to resolve the controversy by measuring D2BP using both [18F]fallypride and [11C]raclopride in 39 adults, 13 within each of three BMI strata to represent a large BMI range, under controlled overnight fasting conditions following a period of dietary stabilization. The primary aims are to estimate the mathematical relationship between striatal D2BP and BMI and determine the within-subject correlations of D2BP derived from [18F]fallypride and [11C]raclopride.

Drug: [18F]fallypride
The present study will attempt to resolve the controversy by measuring D2BP using both [18F]fallypride and [11C]raclopride in 39 adults, 13 within each of three BMI strata to represent a large BMI range, under controlled overnight fasting conditions following a period of dietary stabilization. The primary aims are to estimate the mathematical relationship between striatal D2BP and BMI and determine the within-subject correlations of D2BP derived from [18F]fallypride and [11C]raclopride.




Primary Outcome Measures :
  1. To determine the effect of palatable meal consumption on D2BP in individuals with a wide BMI range. Binding potential estimates will be estimated within subjects using [11C]raclopride [ Time Frame: 6 months ]
    The primary aims are to estimate the mathematical relationship between striatal D2BP and BMI and determine the within-subject correlations of D2BP derived from [18F]fallypride and [11C]raclopride.

  2. To determine if D2BP is related to BMI and whether there is a linear or quadratic relationship [ Time Frame: 6 months ]
    The primary aims are to estimate the mathematical relationship between striatal D2BP and BMI and determine the within-subject correlations of D2BP derived from [18F]fallypride and [11C]raclopride.

  3. To determine correlations between D2BP, as measured by [18F]fallypride and [11C]raclopride time-activity curves. [ Time Frame: 6 months ]
    The primary aims are to estimate the mathematical relationship between striatal D2BP and BMI and determine the within-subject correlations of D2BP derived from [18F]fallypride and [11C]raclopride.


Secondary Outcome Measures :
  1. Investigate the metabolic and endocrine correlates of brain dopamine D2BP and neural bases of food perception and preference [ Time Frame: 1 year ]
    Following admission for Phase B, volunteers will undergo metabolic measurements consisting of: body weight and height; measurement of body composition (e.g., dual energy x-ray absorptiometry (DEXA), air-displacement plethysmography (BodPod)) and they will complete a battery of self-report questionnaires and computer tasks related to mood, stress, thoughts about food and eating, and self-control. Female subjects of reproductive potential will also complete a urine pregnancy test on Day 1 of the inpatient visit and interviewed about the possibility of pregnancy. Positive test results will preclude subjects from further participation. The purpose of these measurements is to facilitate examination of exploratory aims by providing a comprehensive assessment of whole-body composition in the subjects, as well as measures of cognitive processes that subserve typical food intake and feeding behaviors

  2. Investigate the behavioral correlates of brain dopamine D2BP such as free-living physical activity, ad libitum meal consumption, and body weight changes over a one year period. [ Time Frame: 1 year ]
    2.Investigate the metabolic and endocrine correlates of brain dopamine D2BP and neural bases of food perception and preference

  3. Investigate the associations between brain dopamine D2BP and neural bases of food perception and preference [ Time Frame: 1 year ]
    Following admission for Phase B, volunteers will undergo metabolic measurements consisting of: body weight and height; measurement of body composition (e.g., dual energy x-ray absorptiometry (DEXA), air-displacement plethysmography (BodPod)) and they will complete a battery of self-report questionnaires and computer tasks related to mood, stress, thoughts about food and eating, and self-control. Female subjects of reproductive potential will also complete a urine pregnancy test on Day 1 of the inpatient visit and interviewed about the possibility of pregnancy. Positive test results will preclude subjects from further participation. The purpose of these measurements is to facilitate examination of exploratory aims by providing a comprehensive assessment of whole-body composition in the subjects, as well as measures of cognitive processes that subserve typical food intake and feeding behaviors



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:
  • Age 18-45 years, male and female
  • Consent to undergoing PET scanning
  • Body mass index (BMI) greater than or equal to 18.5 kg/m^2
  • Weight stable (less than plus or minus 5% change in the past month)
  • Written informed consent
  • Estimated IQ greater than or equal to 70, as determined by the NART (Scores below 70 are indicative of mental retardation; IQ has been related to alterations in brain structure and function that may confound neuroimaging measures. Failure to meet this eligibility criteria will be documented in the record and communicated to the potential participant as ineligibility based on reading test results )

EXCLUSION CRITERIA:

  • Age 46 or greater (Age is a significant confound in the relationship between BMI and dopamine. Dopamine binding has been shown to drastically decrease in the fifth decade of life.
  • Body weight > 400 lbs. (weight limit of PET scanner)
  • Weigh less than 80% of maximum lifetime weight
  • BMI < 18.5 kg/m2
  • Past or present history of neurological or psychiatric disease (e.g., depression, anxiety, substance use disorder or psychosis), or eating disorders (e.g., anorexia nervosa, bulimia nervosa, or binge eating disorder) as determined by research team upon review of

history/physica l, Eating Disorder Examination-Questionna ire and Self-Rated Level 1 Cross-Cutting Symptom Measure.

  • Blood pressure >140/90 mm Hg
  • Evidence/history of cancer, metabolic disease (e.g. thyroid disease, diabetes) or cardiovascular disease (e.g. coronary artery disease, myocardial infarction, stroke, atherosclerosis), or disease that may influence metabolism
  • Current use of prescription medication or other drug that may influence metabolism (diet/weight-loss medication, asthma medication, psychiatric medications such as antidepressants, anti-anxiety medications, and stimulants for ADHD, corticosteroids or other medications at the discretion of the PI and/or study team)
  • Pregnancy, lactation at any time during study/follow-up period (women only)
  • Evidence of vigorous exercising in order to lose weight, change body shape, or to counteract the effects of eating
  • Previous bariatric surgery
  • Evidence of nicotine dependence as determined by Fagerstrom scoregreater than or equal to 3 (including chewing or smoking tobacco), any drug use (amphetamines, cocaine, heroin, marijuana), or problematic alcohol use (i.e. diagnosis of alcohol use disorder: meeting greater than or equal to 2 of 11 criteria in past 12 months, ranging from drinking more/longer than intended to experiencing

withdrawal symptoms); report of binge drinking: greater than or equal to 5 drinks in 2 hours or greater than or equal 4 drinks in

2 hours for men and women, respectively) over the previous 6 months.

  • Volunteers with strict dietary concerns (e.g. kosher diet, milk allergy or lactose intolerance, or food allergies)
  • Caffeine consumption > 300 mg/day (roughly greater than or equal to 3 cups coffee or 2-3 energy drinks)
  • Having metal implants incompatible with MRI (for example, pacemakers, metallic prostheses such as cochlear implants or heart valves, shrapnel fragments, etc.).
  • Having had previous radiation exposure within the last year for either medical or research purposes (e.g. X-rays, PET scans, etc.) that would exceed research limits. Excessive radiation exposure will be determined at the discretion of the PI and/or study team
  • Are claustrophobic to a degree that they would feel uncomfortable in the MRI machine.
  • Non-English speakers.
  • Cannot commit to the schedule of visits to the Clinical Research Center as required by the study timeline

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03648892


Contacts
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Contact: Michael S Stagliano, C.R.N.P. (301) 827-3198 michael.stagliano@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Kevin Hall, Ph.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Additional Information:
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Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT03648892    
Other Study ID Numbers: 180132
18-DK-0132
First Posted: August 28, 2018    Key Record Dates
Last Update Posted: October 8, 2021
Last Verified: October 6, 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ):
Dopamine Response
Energy Expenditure
Neurocognitive Function
Obesity
Additional relevant MeSH terms:
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Obesity
Overweight
Overnutrition
Nutrition Disorders
Body Weight
Raclopride
Fallypride
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Dopamine D2 Receptor Antagonists