Brain Dopamine Function in Human Obesity

Early Phase 1

Completed

Conditions: Healthy Volunteers
Obesity
Overweight

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

Registration Number: NCT03648892

Lead Sponsor: 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....

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 61

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Main	[18F]fallypride	Healthy volunteers, within three BMI strata, under controlled overnight fasting conditions following a period of dietary stabilization
Main	[c11] raclopride	Healthy volunteers, within three BMI strata, under controlled overnight fasting conditions following a period of dietary stabilization

Primary Outcome Measures

Name	Time	Method
Change in Striatal Dopamine D2BP After a Palatable Meal	assessed at Days 2-5	To determine the effect of palatable meal consumption on striatal D2BP using \[11C\]Raclopride
Correlation Between Change in Striatal Dopamine D2BP After a Palatable Meal and BMI	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
Relationship Between Striatal D2BP and BMI is Quadratic or Linear	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.
Correlation Between Striatal D2 Receptor Binding Potential (D2BP) as Measured by [18F]Fallypride and [11C]Raclopride Time-activity Curves	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.

Secondary Outcome Measures

Name	Time	Method
Associations Between Brain Metabolite GABA Via MRS and Striatal D2BP Via [18F]Fallypride	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.
Associations Between Behavioral Performance on Food Go/No Go Computer Task and Striatal D2BP	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.
Associations Between ad Libitum Meal Consumption and Striatal D2 Receptor (D2R)	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