Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lean controls | Active Comparator | Lean complete baseline outcome measures only |
|
| Obese | Experimental | Obese completing baseline and post-VLCD outcome measures |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Binge Eating Score Questionnaire | Increased scores indicate increased binge eating behaviors. Score 0-46 | Baseline |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Julia P Dunn, MD | Vanderbilt University Medical Center | Principal Investigator |
| Robert M Kessler, MD | Vanderbilt University Medical Center | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30849082 | Derived | 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. | |
| 28944597 | 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. |
Not provided
Not provided
Not provided
9 lean enroll but only 8 complete. The lean complete study after baseline outcome measurements.
19 obese enroll but only 18 complete baseline outcome measurements and of these 15 completed the VLCD and post-outcome measurements
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Lean | BMI<~25kg/m2 |
| FG001 | Obese | BMI>/=30kg/m2 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Lean | |
| BG001 | Obese | |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Striatal DRD2 Receptor Binding | Region of interest compared to reference region to calculate binding potential | Baseline outcome measurements are compared between lean and obese. Baseline and post outcome measurements are compared for the obese who completed VLCD | Posted | Mean | Standard Deviation | ratio | Baseline and after 8-10days VLCD |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lean | 0 |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Julia Dunn, MD | Vanderbilt University | 615-343-8389 | julia.dunn@va.gov |
Not provided
| ID | Term |
|---|---|
| D009765 | Obesity |
| D007333 | Insulin Resistance |
| D005247 | Feeding Behavior |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D009682 | Magnetic Resonance Spectroscopy |
| D005951 | Glucose Tolerance Test |
| D011788 | Quality of Life |
| D031204 | Caloric Restriction |
| ID | Term |
|---|---|
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
| D001774 | Blood Chemical Analysis |
Not provided
Not provided
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 .
Not provided
Not provided
Not provided
Not provided
| 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 |
|
| 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 |
|
| 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 |
|
| Caloric Restriction | Other | Obese participants only complete a short-term (~10days) very low calorie diet |
|
| 26599819 | 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. |
| 22432117 | 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. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| BMI | Mean | Standard Deviation | kg/m2 |
|
| Beck Depression Inventory II(BDI-II) | 0-63 with higher scores indicating increased depressive symptoms. Scores above 20 indicate moderate depressive symptoms. | Mean | Standard Deviation | scores on a scale |
|
| OGTT_SI (Insulin Sensitivity from OGTT) | Insulin Sensitivity from Oral Glucose Tolerance Test was estimated using the oral minimal model method | Mean | Standard Deviation | (10-4min-1/µU*mL) |
|
| Insulin | Mean | Standard Deviation | (µU/ml) |
|
| Glucose | Mean | Standard Deviation | mg/dl |
|
| Leptin | Mean | Standard Deviation | ng/ml |
|
| Acyl Ghrelin | Mean | Standard Deviation | pg/ml |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Primary | Insulin | microU/ml | Posted | Mean | Standard Deviation | microU/ml | Baseline to post 8-10days after VLCD |
|
|
|
| Primary | Glucose | Posted | Mean | Standard Deviation | mg/dL | Baseline to post 8-10days after VLCD |
|
|
|
| Primary | Leptin | Posted | Mean | Standard Deviation | ng/ml | Baseline to post 8-10days after VLCD |
|
|
|
| Primary | Acyl Ghrelin | Posted | Mean | Standard Deviation | pg/ml | Baseline to post 8-10days after VLCD |
|
|
|
| Primary | Insulin Sensitivity From Oral Glucose Tolerance Test (OGTT_SI) | Insulin Sensitivity from Oral Glucose Tolerance Test was estimated using the minimal model method | 9 lean enroll but only 8 complete. A ll lean complete study after baseline outcome measurements. 19 obese enroll but only 18 complete baseline studies and of these 15 completed the VLCD | Posted | Mean | Standard Deviation | 10-4*min-1*microU-1*mL | Baseline to post 8-10days after VLCD |
|
|
|
| Secondary | Binge Eating Score Questionnaire | Increased scores indicate increased binge eating behaviors. Score 0-46 | Posted | Mean | Standard Deviation | score from questionnaire | Baseline |
|
|
|
| 9 |
| 0 |
| 9 |
| EG001 | Obese | 0 | 19 | 0 | 19 |
Not provided
Not provided
Not provided
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D001522 | Behavior, Animal |
| D001519 | Behavior |
| D019963 | Clinical Chemistry Tests |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D003940 | Diagnostic Techniques, Endocrine |
| D006304 | Health Status |
| D003710 | Demography |
| D015991 | Epidemiologic Measurements |
| D011634 | Public Health |
| D004778 | Environment and Public Health |
| D004035 | Diet Therapy |
| D044623 | Nutrition Therapy |
| D013812 | Therapeutics |
| D002149 | Energy Intake |
| D004032 | Diet |
| D009747 | Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |