Dopamine and Insulin Resistance
March 29, 2017 updated by: Julia P.Dunn,MD, Vanderbilt University
Dopamine Receptor Availability and Insulin Resistance
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
Study Overview
Status
Completed
Conditions
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.
Study Type
Interventional
Enrollment (Actual)
28
Phase
- Not Applicable
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
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center
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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
Ages Eligible for Study
18 years to 60 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
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: Other
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Active Comparator: Lean controls
Lean complete baseline outcome measures only
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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
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
An MRI of the brain and abdomen will be performed prior to PET scan One time at baseline in both lean and obese
A series of short psychological scales will be administered during the study.
Completed at baseline
|
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Experimental: Obese
Obese completing baseline and post-VLCD outcome measures
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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
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
An MRI of the brain and abdomen will be performed prior to PET scan One time at baseline in both lean and obese
A series of short psychological scales will be administered during the study.
Completed at baseline
Obese participants only complete a short-term (~10days) very low calorie diet
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Striatal DRD2 Receptor Binding
Time Frame: Baseline and after 8-10days VLCD
|
Region of interest compared to reference region to calculate binding potential
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Baseline and after 8-10days VLCD
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Insulin
Time Frame: Baseline to post 8-10days after VLCD
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microU/ml
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Baseline to post 8-10days after VLCD
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Glucose
Time Frame: Baseline to post 8-10days after VLCD
|
Baseline to post 8-10days after VLCD
|
|
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Leptin
Time Frame: Baseline to post 8-10days after VLCD
|
Baseline to post 8-10days after VLCD
|
|
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Acyl Ghrelin
Time Frame: Baseline to post 8-10days after VLCD
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Baseline to post 8-10days after VLCD
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|
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Insulin Sensitivity From Oral Glucose Tolerance Test (OGTT_SI)
Time Frame: Baseline to post 8-10days after VLCD
|
Insulin Sensitivity from Oral Glucose Tolerance Test was estimated using the minimal model method
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Baseline to post 8-10days after VLCD
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Binge Eating Score Questionnaire
Time Frame: Baseline
|
Increased scores indicate increased binge eating behaviors.
Score 0-46
|
Baseline
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Julia P Dunn, MD, Vanderbilt University Medical Center
- Study Director: Robert M Kessler, MD, Vanderbilt University Medical Center
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.
General Publications
- Garcia AE, Kasim N, Tamboli RA, Gonzalez RS, Antoun J, Eckert EA, Marks-Shulman PA, Dunn J, Wattacheril J, Wallen T, Abumrad NN, Flynn CR. Lipoprotein Profiles in Class III Obese Caucasian and African American Women with Nonalcoholic Fatty Liver Disease. PLoS One. 2015 Nov 23;10(11):e0142676. doi: 10.1371/journal.pone.0142676. eCollection 2015.
- Dunn JP, Abumrad NN, Patterson BW, Kessler RM, Tamboli RA. Brief communication: beta-cell function influences dopamine receptor availability. PLoS One. 2019 Mar 8;14(3):e0212738. doi: 10.1371/journal.pone.0212738. eCollection 2019.
- Dunn JP, Abumrad NN, Kessler RM, Patterson BW, Li R, Marks-Shulman P, Tamboli RA. Caloric Restriction-Induced Decreases in Dopamine Receptor Availability are Associated with Leptin Concentration. Obesity (Silver Spring). 2017 Nov;25(11):1910-1915. doi: 10.1002/oby.22023. Epub 2017 Sep 25.
- Dunn JP, Kessler RM, Feurer ID, Volkow ND, Patterson BW, Ansari MS, Li R, Marks-Shulman P, Abumrad NN. Relationship of dopamine type 2 receptor binding potential with fasting neuroendocrine hormones and insulin sensitivity in human obesity. Diabetes Care. 2012 May;35(5):1105-11. doi: 10.2337/dc11-2250. Epub 2012 Mar 19.
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
December 1, 2008
Primary Completion (Actual)
April 1, 2011
Study Completion (Actual)
December 1, 2012
Study Registration Dates
First Submitted
December 2, 2008
First Submitted That Met QC Criteria
December 3, 2008
First Posted (Estimate)
December 4, 2008
Study Record Updates
Last Update Posted (Actual)
May 10, 2017
Last Update Submitted That Met QC Criteria
March 29, 2017
Last Verified
March 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB#080861 and 061246
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.