Brain Dopamine Function in Human Obesity

NCT03648892 | Completed Early Phase 1 Results FDA Drug

• 2 other identifiers: 18013218-DK-0132
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

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....

Conditions

Obesity; Healthy Volunteers; Overweight

Keywords

Dopamine Response; Energy Expenditure; Neurocognitive Function; Obesity

Outcome Measures

Primary Outcomes (4)

• Correlation Between Striatal D2 Receptor Binding Potential (D2BP) as Measured by [18F]Fallypride and [11C]Raclopride Time-activity Curves

  Correlations between striatal D2BP via \[18F\]Fallypride and striatal D2BP via \[11C\]Raclopride is obtained. Pearson's correlation coefficient is used with a possible range between -1 to 1 indicating strong association in the same direction as correlation is closer to 1, strong association in opposite direction as correlation is closer to -1, and no association as correlation is closer to 0.

  assessed at Days 2-5

• Relationship Between Striatal D2BP and BMI is Quadratic or Linear

  Coefficient estimate of the quadratic term of BMI in quadratic regression is obtained and Coefficient estimate of the linear term of BMI in simple linear regression is obtained.

  assessed at Days 2-5

• Change in Striatal Dopamine D2BP After a Palatable Meal

  To determine the effect of palatable meal consumption on striatal D2BP using \[11C\]Raclopride

  assessed at Days 2-5

• Correlation Between Change in Striatal Dopamine D2BP After a Palatable Meal and BMI

  To determine association between change in striatal dopamine D2BP after a palatable meal consumption and BMI. Binding potential estimates will be estimated within subjects using \[11C\]Raclopride

  assessed at Days 2-5

Secondary Outcomes (3)

• Associations Between Behavioral Performance on Food Go/No Go Computer Task and Striatal D2BP

  assessed at Days 2-5

• Associations Between ad Libitum Meal Consumption and Striatal D2 Receptor (D2R)

  assessed at Days 2-5

• Associations Between Brain Metabolite GABA Via MRS and Striatal D2BP Via [18F]Fallypride

  assessed at Days 2-5

Study Arms (1)

Main

OTHER

Healthy volunteers, within three BMI strata, under controlled overnight fasting conditions following a period of dietary stabilization

Drug: [c11] raclopride; Drug: [18F]fallypride

Interventions

[c11] raclopride DRUG

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.

Main

[18F]fallypride DRUG

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.

Main

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 intelligence quotient (IQ) greater than or equal to 70, as determined by the National Adult Reading Test (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 )

You may not qualify if:

• 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/physical, Eating Disorder Examination-Questionnaire 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 attention-deficit/hyperactivity disorder (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 score greater 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
• 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)

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Darcey VL, Guo J, Chi M, Chung ST, Courville AB, Gallagher I, Herscovitch P, Howard R, La Noire M, Milley L, Schick A, Stagliano M, Turner S, Urbanski N, Yang S, Yim E, Zhai N, Zhou MS, Hall KD. Striatal dopamine tone is positively associated with adiposity in humans as determined by PET using dual dopamine type-2 receptor antagonist tracers. Mol Psychiatry. 2025 Aug;30(8):3708-3717. doi: 10.1038/s41380-025-02960-y. Epub 2025 Apr 6.

  PMID: 40188315 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Obesity; Overweight

Interventions

Raclopride; N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Chlorobenzoates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Dr. Kevin Hall
• Organization: NIH

kevinh@niddk.nih.gov

301-402-8248

Study Officials

• Kevin Hall, Ph.D.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2018
• First Posted: August 28, 2018
• Study Start: September 21, 2018
• Primary Completion: March 31, 2022
• Study Completion: February 17, 2023
• Last Updated: July 11, 2023
• Results First Posted: May 3, 2023

Record last verified: 2022-05

Locations

US (1)