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Dopamine and Insulin Resistance

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Julia P.Dunn,MD, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00802204
First received: December 2, 2008
Last updated: March 29, 2017
Last verified: March 2017
  Purpose
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

Condition Intervention
Obesity Radiation: PET scan Procedure: Oral glucose tolerance test Procedure: MRI Behavioral: Psychological scales to assess attitudes and behaviors related to eating and quality of life Other: Caloric Restriction

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention 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: No masking
Primary Purpose: Other
Official Title: Dopamine Receptor Availability and Insulin Resistance

Resource links provided by NLM:


Further study details as provided by Julia P.Dunn,MD, Vanderbilt University:

Primary Outcome Measures:
  • Striatal DRD2 Receptor Binding [ Time Frame: Baseline and after 8-10days VLCD ]
    Region of interest compared to reference region to calculate binding potential

  • Insulin [ Time Frame: Baseline to post 8-10days after VLCD ]
    microU/ml

  • Glucose [ Time Frame: Baseline to post 8-10days after VLCD ]
  • Leptin [ Time Frame: Baseline to post 8-10days after VLCD ]
  • Acyl Ghrelin [ Time Frame: Baseline to post 8-10days after VLCD ]
  • 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


Secondary Outcome Measures:
  • Binge Eating Score Questionnaire [ Time Frame: Baseline ]
    Increased scores indicate increased binge eating behaviors. Score 0-46


Enrollment: 28
Study Start Date: December 2008
Study Completion Date: December 2012
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lean controls
Lean complete baseline outcome measures only
Radiation: 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

Procedure: 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
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
Behavioral: 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
Experimental: Obese
Obese completing baseline and post-VLCD outcome measures
Radiation: 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

Procedure: 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
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
Behavioral: 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
Other: Caloric Restriction
Obese participants only complete a short-term (~10days) very low calorie diet

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.
  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00802204

Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Julia P Dunn, MD Vanderbilt University Medical Center
Study Director: Robert M Kessler, MD Vanderbilt University Medical Center
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Julia P.Dunn,MD, Physician, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00802204     History of Changes
Other Study ID Numbers: IRB#080861 and 061246
Study First Received: December 2, 2008
Results First Received: July 14, 2016
Last Updated: March 29, 2017

Keywords provided by Julia P.Dunn,MD, Vanderbilt University:
Obesity
Insulin Resistance
Neuroendocrine regulation
Eating behaviors
Dopamine signaling

Additional relevant MeSH terms:
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Dopamine
Dopamine Agents
Hypoglycemic Agents
Physiological Effects of Drugs
Cardiotonic Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on August 16, 2017