fMRI and Appetite-Related Hormones Pre and Post Obesity Surgery

Obesity Clinical Trial

Official title:

Functional Brain Imaging and Appetite-Related Hormones Pre and Post Obesity Surgery

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT01583725
• Other study ID #: 09-101
• Status: Enrolling by invitation
• Phase: N/A
• First received: March 9, 2012
• Last updated: January 10, 2014
• Start date: July 2010
• Est. completion date: July 2015

Study information

• Verified date: January 2014
• Source: New York Obesity and Nutrition Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The investigators are looking at the differences in appetite and obesity between weight loss participants and patients undergoing bariatric surgery.

Obese persons between the ages of 18 & 65 are eligible to participate in this study, whether or not they intend to undergo bariatric surgery.

Description:

Currently, the only effective long term treatment for severe obesity is bariatric surgery.2 Nearly 200,000 procedures are performed each year, with this number increasing rapidly.3 However, the mechanisms of reduced food intake and weight loss after obesity surgery, particularly Rouen-Y gastric bypass (RYGB), are not well understood. This study utilizes functional magnetic resonance imaging (fMRI) and measures of appetite-related gut peptide levels pre and post bariatric surgery to investigate the neurological and hormonal mechanisms involved in initiation and termination of meals.

The general objective is to better understand the physiological changes resulting in weight loss from obesity surgery, particularly Roux-en-Y gastric bypass (RYGB). The main hypothesis is that the differential mechanisms of action in RYGB will alter the signals involved in the initiation and termination of meals, reflected by changes in both peptide hormone levels and regional brain activity in response to foods. The investigators anticipate that the trigger for meal initiation by potent food stimuli will be diminished following RYGB, as indicated by reduced brain activation in areas associated with food reward and motor planning, including the orbitofrontal cortex (OFC). RYGB will be compared to: a. Gastric Banding (GB), representing the restrictive component of surgery, which itself enhances fullness, but in the absence of any rerouting of the gut, should result in fewer changes in gut peptide levels and brain activation; b. Weight Loss (WL) on a formula diet over 3 mo, which represents the weight loss component of surgery; and c. No Treatment (NT), a general control, with no gastric restriction or weight loss. These group comparisons will help parse the contributions of RYGB surgery to weight loss.

The plan is to study clinically severe obese subjects (S's) pre surgery, and at 3 and 18 mo post surgery. The investigators will examine: 1) fMRI brain activation in response to food stimuli and 2) appetite-related gut peptide levels before and following a fixed meal prior to the fMRI. The findings should reveal potential mechanisms associated with the changes in appetite, eating behaviors, and body weight, both during the rapid weight loss phase at 3 mo post surgery as well as when weight typically stabilizes at a nadir at 18 mo post surgery. The investigators plan to enroll 160 patients: 40 with RYGB, 40 GB, 40 WL, and 40 NT (4-arm study). S's will be within the BMI range of 40-50 and matched across groups for BMI, gender (3:1, f:m), and BED status.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 160
• Est. completion date: July 2015
• Est. primary completion date: July 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• BMI range 35-50 kg/m^2

Exclusion Criteria:

• diabetes,

• smoking,

• pregnancy

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Obesity

Intervention

Procedure:
• Liquid meal responses
Subject ingests a meal-replacement shake and gut peptide levels are measured before and after intake.

Behavioral:
• fMRI responses to food-cues
Subjects undergo a 40 min fMRI neuroimaging session while receiving auditory and visual food cues.

Locations

Country	Name	City	State
United States	St. Luke's-Roosevelt Hospital Center	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
New York Obesity and Nutrition Research Center	Columbia University, St. Luke's-Roosevelt Hospital Center

Country where clinical trial is conducted

United States, 

References & Publications (14)

Erdmann J, Töpsch R, Lippl F, Gussmann P, Schusdziarra V. Postprandial response of plasma ghrelin levels to various test meals in relation to food intake, plasma insulin, and glucose. J Clin Endocrinol Metab. 2004 Jun;89(6):3048-54. — View Citation

Geliebter A, Ladell T, Logan M, Schneider T, Sharafi M, Hirsch J. Responsivity to food stimuli in obese and lean binge eaters using functional MRI. Appetite. 2006 Jan;46(1):31-5. Epub 2005 Dec 20. Erratum in: Appetite. 2006 May;46(3):395. Schweider, Tzipporah [corrected to Schneider, Tzipporah]. — View Citation

Hosoda H, Doi K, Nagaya N, Okumura H, Nakagawa E, Enomoto M, Ono F, Kangawa K. Optimum collection and storage conditions for ghrelin measurements: octanoyl modification of ghrelin is rapidly hydrolyzed to desacyl ghrelin in blood samples. Clin Chem. 2004 Jun;50(6):1077-80. — View Citation

Jirik-Babb P, Geliebter A. Comparison of psychological characteristics of binging and nonbinging obese, adult, female outpatients. Eat Weight Disord. 2003 Jun;8(2):173-7. — View Citation

Korner J, Bessler M, Cirilo LJ, Conwell IM, Daud A, Restuccia NL, Wardlaw SL. Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin, peptide YY, and insulin. J Clin Endocrinol Metab. 2005 Jan;90(1):359-65. Epub 2004 Oct 13. — View Citation

Le DS, Pannacciulli N, Chen K, Del Parigi A, Salbe AD, Reiman EM, Krakoff J. Less activation of the left dorsolateral prefrontal cortex in response to a meal: a feature of obesity. Am J Clin Nutr. 2006 Oct;84(4):725-31. — View Citation

Le DS, Pannacciulli N, Chen K, Salbe AD, Del Parigi A, Hill JO, Wing RR, Reiman EM, Krakoff J. Less activation in the left dorsolateral prefrontal cortex in the reanalysis of the response to a meal in obese than in lean women and its association with successful weight loss. Am J Clin Nutr. 2007 Sep;86(3):573-9. Erratum in: Am J Clin Nutr. 2008 Feb;87(2):463. Del Parigi, Angelo [added]. — View Citation

le Roux CW, Welbourn R, Werling M, Osborne A, Kokkinos A, Laurenius A, Lönroth H, Fändriks L, Ghatei MA, Bloom SR, Olbers T. Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Ann Surg. 2007 Nov;246(5):780-5. — View Citation

Liu J, Prudom CE, Nass R, Pezzoli SS, Oliveri MC, Johnson ML, Veldhuis P, Gordon DA, Howard AD, Witcher DR, Geysen HM, Gaylinn BD, Thorner MO. Novel ghrelin assays provide evidence for independent regulation of ghrelin acylation and secretion in healthy young men. J Clin Endocrinol Metab. 2008 May;93(5):1980-7. doi: 10.1210/jc.2007-2235. Epub 2008 Mar 18. — View Citation

Marzullo P, Verti B, Savia G, Walker GE, Guzzaloni G, Tagliaferri M, Di Blasio A, Liuzzi A. The relationship between active ghrelin levels and human obesity involves alterations in resting energy expenditure. J Clin Endocrinol Metab. 2004 Feb;89(2):936-9. — View Citation

Ongür D, Price JL. The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb Cortex. 2000 Mar;10(3):206-19. Review. — View Citation

Rosenbaum M, Leibel RL, Hirsch J. Obesity. N Engl J Med. 1997 Aug 7;337(6):396-407. Review. Erratum in: N Engl J Med 1998 Feb 19;338(3):555. — View Citation

Sorbara M, Geliebter A. Body image disturbance in obese outpatients before and after weight loss in relation to race, gender, binge eating, and age of onset of obesity. Int J Eat Disord. 2002 May;31(4):416-23. — View Citation

Whitson BA, Leslie DB, Kellogg TA, Maddaus MA, Buchwald H, Billington CJ, Ikramuddin S. Entero-endocrine changes after gastric bypass in diabetic and nondiabetic patients: a preliminary study. J Surg Res. 2007 Jul;141(1):31-9. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in brain activation in response to visual and auditory food cues	Measures of brain brain activation in areas associated with food reward and motor planning, including the orbitofrontal cortex (OFC). Over the course of 40-min fMRI scans, we will compare change in activation from 3 mo pre-surgery to 3 and 18 mo post-surgery, and predict a post-surgical decrease in activation in such regions.	3 mo pre-surgery and 3 and 18 mo post-surgery	No
Secondary	Anthropometrics and Body Composition	Height and weight will be assessed using a stadiometer and digital scale. Sagittal diameter and waist and hip circumferences, as well as maximum supine width, will be measured. Waist circumference will be measured. Air displacement (Bioelectrical impedance analyses) will also be performed to obtain lean and fat mass. Weights, BMI, and body composition will confirm that the four obese groups are similar at baseline and provide estimates of changes in body fat following treatment.	3 mo pre-surgery and 3 and 18 mo post-surgery	No
Secondary	Mood Measures	We will administer relevant psychological instruments to assess Mood: The Inventory of Depressive Symptomatology-Self Report (IDS-SR)will be assessed at 3mo pre-surgery, 3mo, 6mo and 18mo post surgery.	3 mo pre-surgery and 3 and 18 mo post-surgery	No
Secondary	Change in appetite-related gut peptide levels	We will measure changes in appetite-related gut peptide levels before and following a fixed meal prior to the fMRI. This will be assessed via blood plasma samples taken on 3 occasions: 3 mo pre-surgery, 3 mo post-surgery, and 18 mo post-surgery. At each session, there will be multiple time points: -15, 0, 15, 30, 60, and 90 minutes before/after ingestion of a meal replacement shake.	3 mo pre-surgery and 3 and 18 mo post-surgery	No
Secondary	Eating Behavior	We will administer relevant psychological instruments to assess Eating Behavior:including Eating Disorder Examination (EDE) to diagnose BED; Binge Eating Scale (BES), correlated with BED status; eating-related behavior (DEBQ - Restraint, Emotional, and Externality subscales); and dietary intake (24-Hour Food Recall).	3 mo pre-surgery and 3 and 18 mo post-surgery	No

External Links

•   New York Obesity Nutrition Research Center website