Brain Dopamine Function in Human Obesity

June 22, 2023 updated by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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....

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
61

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

  • 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 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 )

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/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

    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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Main
Healthy volunteers, within three BMI strata, under controlled overnight fasting conditions following a period of dietary stabilization
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Correlation Between Striatal D2 Receptor Binding Potential (D2BP) as Measured by [18F]Fallypride and [11C]Raclopride Time-activity Curves
Time Frame: assessed at Days 2-5

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
Change in Striatal Dopamine D2BP After a Palatable Meal
Time Frame: assessed at Days 2-5
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
Time Frame: assessed at Days 2-5
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
Relationship Between Striatal D2BP and BMI is Quadratic or Linear
Time Frame: assessed at Days 2-5
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

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Associations Between ad Libitum Meal Consumption and Striatal D2 Receptor (D2R)
Time Frame: assessed at Days 2-5
Exploratory analyses of correlations between eating behavior measured by ad libitum food intake at a single meal and striatal D2R via [18F]Fallypride and via [11C]Raclopride
assessed at Days 2-5
Associations Between Behavioral Performance on Food Go/No Go Computer Task and Striatal D2BP
Time Frame: assessed at Days 2-5

Exploratory analyses of correlations between behavioral performance on Food Go/No Go computer task measured by No Go accuracy as commission errors and striatal D2BP via [18F]Fallypride and via [11C]Raclopride.

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
Associations Between Brain Metabolite GABA Via MRS and Striatal D2BP Via [18F]Fallypride
Time Frame: assessed at Days 2-5

Exploratory analyses of correlations between brain metabolite GABA via magnetic resonance spectroscopy (MRS) and striatal D2BP via [18F]Fallypride.

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kevin Hall, Ph.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 21, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 17, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 24, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 25, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 28, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 11, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 22, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 180132
  • 18-DK-0132

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Obesity

Clinical Trials on [c11] raclopride

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings