Dopamine and Insulin Resistance

Dopamine Receptor Availability and Insulin Resistance

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00802204

Enrollment

Registered

2008-12-04

Start date

2008-12-31

Completion date

2012-12-31

Last updated

2017-05-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obesity

Keywords

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

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

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.

Interventions

RADIATIONPET 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

PROCEDUREOral 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

PROCEDUREMRI

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

BEHAVIORALPsychological 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

OTHERCaloric Restriction

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

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

OTHER

Masking

NONE

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 .

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Glucose	Baseline to post 8-10days after VLCD	—
Striatal DRD2 Receptor Binding	Baseline and after 8-10days VLCD	Region of interest compared to reference region to calculate binding potential
Insulin	Baseline to post 8-10days after VLCD	microU/ml
Insulin Sensitivity From Oral Glucose Tolerance Test (OGTT_SI)	Baseline to post 8-10days after VLCD	Insulin Sensitivity from Oral Glucose Tolerance Test was estimated using the minimal model method
Leptin	Baseline to post 8-10days after VLCD	—
Acyl Ghrelin	Baseline to post 8-10days after VLCD	—

Secondary

Measure	Time frame	Description
Binge Eating Score Questionnaire	Baseline	Increased scores indicate increased binge eating behaviors. Score 0-46

Countries

United States

Participant flow

Recruitment details

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

Participants by arm

Arm	Count
Lean	8
Obese	18
Total	26

Baseline characteristics

Characteristic	Total	Obese	Lean
Acyl Ghrelin	132 pg/ml STANDARD_DEVIATION 106	78 pg/ml STANDARD_DEVIATION 55	235 pg/ml STANDARD_DEVIATION 104
Age, Continuous	39 years STANDARD_DEVIATION 8	39 years STANDARD_DEVIATION 8	41 years STANDARD_DEVIATION 9
Beck Depression Inventory II(BDI-II)	6 scores on a scale STANDARD_DEVIATION 6	7 scores on a scale STANDARD_DEVIATION 6	3 scores on a scale STANDARD_DEVIATION 5
BMI	33 kg/m2 STANDARD_DEVIATION 9	39 kg/m2 STANDARD_DEVIATION 6	23 kg/m2 STANDARD_DEVIATION 2
Glucose	86 mg/dl STANDARD_DEVIATION 8	87 mg/dl STANDARD_DEVIATION 9	82 mg/dl STANDARD_DEVIATION 6
Insulin	14 (µU/ml) STANDARD_DEVIATION 10	18 (µU/ml) STANDARD_DEVIATION 9	6 (µU/ml) STANDARD_DEVIATION 2
Leptin	34 ng/ml STANDARD_DEVIATION 18	43 ng/ml STANDARD_DEVIATION 12	13 ng/ml STANDARD_DEVIATION 5
OGTT_SI (Insulin Sensitivity from OGTT)	6 (10-4min-1/µU*mL) STANDARD_DEVIATION 5	3.98 (10-4min-1/µU*mL) STANDARD_DEVIATION 2.7	11.2 (10-4min-1/µU*mL) STANDARD_DEVIATION 4.1
Race/Ethnicity, Customized African American Participants	8 participants	7 participants	1 participants
Race/Ethnicity, Customized Caucasian Participants	18 participants	11 participants	7 participants
Region of Enrollment United States	26 participants	18 participants	8 participants
Sex: Female, Male Female	26 Participants	18 Participants	8 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants
Weight	91 kg STANDARD_DEVIATION 26	104 kg STANDARD_DEVIATION 17	60 kg STANDARD_DEVIATION 7

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 9	0 / 19
serious Total, serious adverse events	0 / 9	0 / 19