Neurohormonal & Behavioral Correlates of Obesity and Weight Loss

NCT02063451 | Completed

• 2 other identifiers: IWMCNI_015K01DK092322
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity has reached epidemic levels in the United States, and is on the rise in many industrialized nations. The rate of recidivism for long-term weight loss is substantial and presents a critical problem given the importance of obesity as a modifiable risk factor for diseases like type 2 diabetes. Further, the comorbidity of depression with diseases like obesity, type 2 diabetes, and cardiovascular disease suggest that there may be an underlying shared biology for diseases of metabolic dysfunction and emotional dysregulation. The shared biology of these diseases may actually promote the precipitation and exacerbation of comorbid conditions, impacting the success of treatment. Endogenous opioid systems regulate a number of physiological and psychological processes including mood, energy management, and reward. Endogenous opioid µ-receptor-mediated reward processing is thought to be involved both in the short-term control of eating and hedonic food consumption, based on data in animal models. The present proposal will examine the function of the µ-opioid receptor (MOR) system in lean and obese human volunteers following an overnight fast and the change in µ-opioid receptor occupancy (i.e., endogenous opioid release) following the consumption of a standardized meal using PET imaging with the µ-selective radiotracer \[11C\]carfentanil. The obese individuals will be retested in the fasting and fed state following a 15% weight loss with a Very Low Calorie Diet. Further, the investigators will evaluate the function of the MOR system within the context of the individual's metabolic and psychological profile including aspects of mood and inhibitory control. This information will provide the neurobiological bases to develop novel avenues of intervention based on individual variations in central mechanisms associated with motivational systems and appetite and their potential role in weight regain. The investigators hypothesize that overeating in chronically obese individuals will be associated with a dysregulation of MOR system function, manifested by reductions in baseline MOR availability (binding potential, BP) in limbic and reward circuitry, and lower release of endogenous opioids after a standard meal, compared to lean volunteers. The latter is observed as acute reductions in the BP measure after meal ingestion.

Conditions

Obesity

Keywords

Obesity [C18.654.726.500]; Receptor, Opioid, mu [D12.776.543.750.100.620.550]; Brain [A08.186.211]; Affect [F01.470.047]

Outcome Measures

Primary Outcomes (2)

• Change in [11C]carfentanil binding in brain in response to feeding prior to weight loss

  \[11C\]carfentanil is a µ-opioid receptor selective radiotracer for PET imaging that will be used to asses the function of the µ-opioid receptor (MOR) system in the brains of lean and obese human volunteers. Measurements of \[11C\]carfentanil binding will be taken following an overnight fast and following the consumption of a standardized meal to determine the change in µ-opioid receptor occupancy (i.e., endogenous opioid release) in response to feeding.

  baseline and 60 minutes following shake consumption

• Change in [11C]carfentanil binding in brain in response to feeding post weight loss

  \[11C\]carfentanil is a µ-opioid receptor selective radiotracer for PET imaging that will be used to asses the function of the µ-opioid receptor (MOR) system in the brains of obese human volunteers following diet-induced weight loss. Measurements of \[11C\]carfentanil binding will be taken following an overnight fast and following the consumption of a standardized meal to determine the change in µ-opioid receptor occupancy (i.e., endogenous opioid release) in response to feeding. Obese individuals will be retested in the fasting and fed state following a 15% weight loss with a Very Low Calorie Diet which is typically achieved within 6 months.

  baseline and 60 minutes post shake consumption

Secondary Outcomes (2)

• Change in Hunger scores on a visual analog scale in response to feeding at pre weight-loss

  baseline and 120 minutes following shake consumption

• Change in Hunger scores on a visual analog scale in response to feeding post weight-loss

  baseline and 120 minutes following shake consumption

Study Arms (2)

Obese, Weight Loss, Very Low Calorie Diet

OTHER

Obese individuals will a Very Low Calorie Diet (VLCD) using the HMR meal replacement (Health Management Resources, Boston, MA) for 3-6 months until individually targeted weight loss determined by a clinician is reached. Typically, individuals consume 850-1000 kilocalories per day.

Dietary Supplement: Very Low Calorie Diet (VLCD)

Lean, baseline measure

NO INTERVENTION

MOR binding will be observed in lean individuals at one timepoint. Lean individuals will not receive any intervention.

Interventions

Very Low Calorie Diet (VLCD) DIETARY_SUPPLEMENT

Very Low Calorie Diet (VLCD) using the HMR meal replacement (Health Management Resources, Boston, MA). Typically, individuals consume 850-1000 kilocalories per day until a targeted 15% reduction in body weight is achieved.

Obese, Weight Loss, Very Low Calorie Diet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Obese population defined as BMI \> 30 kg/m2.
• Lean population BMI \< 28 but \> 17 kg/m2.
• Able and willing to provide written informed consent for the trial.
• Right handed
• age \>/= 18 years

You may not qualify if:

• Evidence of inherited disorders of lipid metabolism.
• History of Cancer within the last 5 years except for minor skin cancers
• Human immunodeficiency virus (HIV) antibody positive.
• Patients with solid organ transplants.
• Positive pregnancy screen in Women
• Uncontrolled thyroid disease
• Unstable angina or NY heart association class II failure or above
• Gastrointestinal disease specifically GI motility disorders
• Unstable neuropsychiatric disease including major depression/anxiety, eating disorder such as bulimia or anorexia
• End stage renal or hepatic disease
• Autoimmune disorders (e.g. SLE)
• Body weight fluctuation of more than 5 kg in the previous 3 months
• Prior bariatric surgery
• A history or current alcohol/substance abuse, or opoid abuse/use and change in smoking habits or cessation in the past 6 months.
• Any medical condition, which in the opinion of the investigator would make the patient unsuitable for recruitment, or could interfere with the patient participating in or completing the protocol.

Sponsors & Collaborators

• University of Michigan: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• The Brain Research Foundation: collaborator

Study Sites (1)

University of Michigan Medical School

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Paul R Burghardt, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Internal Medicine

Study Record Dates

• First Submitted: February 11, 2014
• First Posted: February 14, 2014
• Study Start: February 1, 2011
• Primary Completion: January 15, 2013
• Study Completion: January 15, 2013
• Last Updated: September 24, 2018

Record last verified: 2018-09

Locations

US (1)