Dopamine and Insulin Resistance

NCT00802204 | Completed Results

• 1 other identifier: IRB#080861 and 061246
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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

Conditions

Obesity

Keywords

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

Outcome Measures

Primary Outcomes (6)

• Striatal DRD2 Receptor Binding

  Region of interest compared to reference region to calculate binding potential

  Baseline and after 8-10days VLCD

• Insulin

  microU/ml

  Baseline to post 8-10days after VLCD

• Glucose

  Baseline to post 8-10days after VLCD

• Leptin

  Baseline to post 8-10days after VLCD

• Acyl Ghrelin

  Baseline to post 8-10days after VLCD

• Insulin Sensitivity From Oral Glucose Tolerance Test (OGTT_SI)

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

  Baseline to post 8-10days after VLCD

Secondary Outcomes (1)

• Binge Eating Score Questionnaire

  Baseline

Study Arms (2)

Lean controls

ACTIVE COMPARATOR

Lean complete baseline outcome measures only

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

Obese

EXPERIMENTAL

Obese completing baseline and post-VLCD outcome measures

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

Interventions

PET scan 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

Lean controls; Obese

Oral glucose tolerance test 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

Lean controls; Obese

MRI PROCEDURE

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

Lean controls; Obese

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

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

Lean controls; Obese

Caloric Restriction OTHER

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

Obese

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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
• Subjects on medications determined by PI, ex. sibutramine, frequent benzodiazepines or related drugs, which could affect quality of study for last 3 months.

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (4)

• 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.

  PMID: 30849082 DERIVED

• 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.

  PMID: 28944597 DERIVED

• 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.

  PMID: 26599819 DERIVED

• 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.

  PMID: 22432117 DERIVED

MeSH Terms

Conditions

Obesity; Insulin Resistance; Feeding Behavior

Interventions

Magnetic Resonance Spectroscopy; Glucose Tolerance Test; Quality of Life; Caloric Restriction

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Behavior, Animal; Behavior

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Health Status; Demography; Epidemiologic Measurements; Public Health; Environment and Public Health; Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Results Point of Contact

• Title: Julia Dunn, MD
• Organization: Vanderbilt University

julia.dunn@va.gov

615-343-8389

Study Officials

• Julia P Dunn, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Robert M Kessler, MD

  Vanderbilt University Medical Center

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician

Model Details: 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 .

Study Record Dates

• First Submitted: December 2, 2008
• First Posted: December 4, 2008
• Study Start: December 1, 2008
• Primary Completion: April 1, 2011
• Study Completion: December 1, 2012
• Last Updated: May 10, 2017
• Results First Posted: May 10, 2017

Record last verified: 2017-03

Locations

US (1)