Dopamine and Insulin Resistance

NCT ID: NCT00802204

Last Updated: 2017-05-10

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-12-31

Study Completion Date

2012-12-31

Brief Summary

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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

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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.

Conditions

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Obesity

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

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 .
Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Lean controls

Lean complete baseline outcome measures only

Group Type ACTIVE_COMPARATOR

PET scan

Intervention Type RADIATION

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

Oral glucose tolerance test

Intervention Type PROCEDURE

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

MRI

Intervention Type PROCEDURE

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

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

Intervention Type BEHAVIORAL

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

Obese

Obese completing baseline and post-VLCD outcome measures

Group Type EXPERIMENTAL

PET scan

Intervention Type RADIATION

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

Oral glucose tolerance test

Intervention Type PROCEDURE

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

MRI

Intervention Type PROCEDURE

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

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

Intervention Type BEHAVIORAL

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

Caloric Restriction

Intervention Type OTHER

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

Interventions

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PET scan

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 RADIATION

Oral glucose tolerance test

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

MRI

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 PROCEDURE

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

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

Intervention Type BEHAVIORAL

Caloric Restriction

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

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Vanderbilt University

OTHER

Sponsor Role lead

Responsible Party

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Julia P.Dunn,MD

Physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Julia P Dunn, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Robert M Kessler, MD

Role: STUDY_DIRECTOR

Vanderbilt University Medical Center

Locations

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Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 30849082 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28944597 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26599819 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22432117 (View on PubMed)

Other Identifiers

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IRB#080861 and 061246

Identifier Type: -

Identifier Source: org_study_id

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