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Dopamine and Insulin Resistance

Primary Purpose

Obesity

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

PET scan

Oral glucose tolerance test

MRI

Psychological scales to assess attitudes and behaviors related to eating and quality of life

Caloric Restriction

About this trial

This is an interventional other trial for Obesity focused on measuring Obesity, Insulin Resistance, Neuroendocrine regulation, Eating behaviors, Dopamine signaling

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Ages 18-60 yrs
obese BMI > 30kg/m2 and Weight less than 350 lbs
lean control BMI 18-25kg/m2

Exclusion Criteria:

Structured exercise > equivalent to 30mins 5x week of walking times a week
History of Substance Abuse, including but exclusive to alcohol, cocaine, marijuana, heroin, nicotine
Current psychiatric disorder or significant h/o disorder
Use or any antidepressants or antipsychotics for last 3-6months or depot antipsychotics in the last 12 months
Any condition felt by PI or co-investigators to interfere with ability to complete the study
Inability to abstain from alcohol, physical exercise or > 1 cup of coffee or equivalent daily for 3 days prior to imaging studies
Significant co-morbidities including atherosclerotic disease, metabolic disease, liver or renal insufficiency or abnormality found on MRI
Any condition which would interfere with MRI or PET studies, e.g. claustrophobia, cochlear implant, metal fragments in eyes, cardiac pacemaker, neural stimulator, tattoos with iron pigment and metallic body inclusions or other metal implanted in the body which may interfere with MRI scanning
Subjects on medications determined by PI, ex. sibutramine, frequent benzodiazepines or related drugs, which could affect quality of study for last 3 months.

Sites / Locations

Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Lean controls

Obese

Arm Description

Lean complete baseline outcome measures only

Obese completing baseline and post-VLCD outcome measures

Outcomes

Primary Outcome Measures

Striatal DRD2 Receptor Binding

Region of interest compared to reference region to calculate binding potential

Insulin

microU/ml

Glucose

Leptin

Acyl Ghrelin

Insulin Sensitivity From Oral Glucose Tolerance Test (OGTT_SI)

Insulin Sensitivity from Oral Glucose Tolerance Test was estimated using the minimal model method

Secondary Outcome Measures

Binge Eating Score Questionnaire

Increased scores indicate increased binge eating behaviors. Score 0-46

Full Information

NCT ID

NCT00802204

First Posted

December 2, 2008

Last Updated

March 29, 2017

Sponsor

Vanderbilt University

1. Study Identification

Unique Protocol Identification Number

NCT00802204

Brief Title

Dopamine and Insulin Resistance

Official Title

Dopamine Receptor Availability and Insulin Resistance

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

December 2008 (undefined)

Primary Completion Date

April 2011 (Actual)

Study Completion Date

December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Vanderbilt University

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Obese individuals have fewer striatal dopamine type 2 receptors (DRD2) than normal weight individuals. Lower DRD2 levels are associated with addiction and a decreased sense of pleasure.Obesity is also associated with insulin resistance (poor insulin action).We propose that insulin resistance and low DRD2 are associated. Using PET imaging,we aim to determine DRD2 binding potential (BP) in the brain is associated with insulin resistance and neuroendocrine hormone levels. Obese participants will be compared to lean, gender and age similar participants. We also aim to determine the effect of caloric restriction on DRD2 BP in obese subjects

Detailed Description

In has been reported obese individuals have fewer striatal dopamine type 2 receptors (DRD2) compared to normal weight individuals congruent with diet induced obese rodent models and similar to models of addiction. Lower DRD2 levels are associated with addiction and a decreased sense of pleasure. Excessive weight gain also contributes to the onset of impaired insulin signaling (insulin resistance). In the brain insulin regulates monoamines and has trophic effects. We propose that the previous reports of low DRD2 in individuals with obesity will be associated with the degree of insulin resistance. Using PET imaging, we aim to determine DRD2 binding potential (BP) in the striatum and hypothesize these measurements will be associated with insulin resistance and potentially other neuroendocrine hormone levels. Obese participants will be compared to lean, sex and age similar participants. We also aim to determine the effect of caloric restriction on DRD2 BP in obese subjects. We hypothesize the caloric restriction will improve insulin resistance and that changes in DRD2 binding will be associated with changes in insulin signaling.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Obesity

Keywords

Obesity, Insulin Resistance, Neuroendocrine regulation, Eating behaviors, Dopamine signaling

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Sequential Assignment

Model Description

Lean who are age and sex similar to obese will complete baseline outcome measurements only. Obese will complete baseline outcome measurements then the VLCD intervention with post outcome measurements .

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lean controls

Arm Type

Active Comparator

Arm Description

Lean complete baseline outcome measures only

Arm Title

Obese

Arm Type

Experimental

Arm Description

Obese completing baseline and post-VLCD outcome measures

Intervention Type

Radiation

Intervention Name(s)

PET scan

Intervention Description

Both lean and obese undergo a PET scan of the brain using the radioligand,fallypride [18F] at baseline. Obese subjects who complete caloric restriction will have repeat scan after diet. Completed at baseline and post-VLCD

Intervention Type

Procedure

Intervention Name(s)

Oral glucose tolerance test

Intervention Description

Subjects will be required to drink a glucose solution; blood samples will be taken over a 5-hour time period Completed at baseline by both lean and obese and in obese post-VLCD

Intervention Type

Procedure

Intervention Name(s)

MRI

Intervention Description

An MRI of the brain and abdomen will be performed prior to PET scan One time at baseline in both lean and obese

Intervention Type

Behavioral

Intervention Name(s)

Psychological scales to assess attitudes and behaviors related to eating and quality of life

Intervention Description

A series of short psychological scales will be administered during the study. Completed at baseline

Intervention Type

Other

Intervention Name(s)

Caloric Restriction

Intervention Description

Obese participants only complete a short-term (~10days) very low calorie diet

Primary Outcome Measure Information:

Title

Striatal DRD2 Receptor Binding

Description

Region of interest compared to reference region to calculate binding potential

Time Frame

Baseline and after 8-10days VLCD

Title

Insulin

Description

microU/ml

Time Frame