Gastric Bypass and Peripheral Activity of the Endocannabinoid System (CCENDO)

Effect of Weight Loss Induced Either by Gastric Bypass or Lifestyle Intervention on the Peripheral Activity of the Endocannabinoid System

The aim of the study is to precise the effect of a large amount of weight loss induced by gastric bypass on the endocannabinoid system (plasma and adipose tissue) of morbidly obese patients and to determine the influence of a gastric bypass surgery compared to a lifestyle intervention with equivalent weight loss on the endocannabinoid system

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Biological: Evaluation of the endocannabinoid system; Procedure: Biopsy of visceral and peripheral adipose tissue; Biological: Evaluation of metabolic parameters; Behavioral: Evolution of behavioral parameters; Behavioral: Dietician consultation; Behavioral: Psychologist consultation

Detailed Description

Dysregulation of the endocannabinoid system has been associated with the development of obesity, metabolic and cardiovascular disorders in both animals and humans.

Obese patients, especially those with abdominal obesity, have significantly higher levels of endocannabinoids. No influence of moderate (5%) body weight loss (induced either by diet intervention or sibutramine) on the peripheral activity of the endocannabinoid system gastric bypass (GB) surgery is the most efficient treatment of obesity Hormonal pathways may participate to the weight reducing effect of the procedure.The endocannabinoid system is present in the gastrointestinal tract.

In animals, sustained weight loss after GB is characterized by reduction of endocannabinoids levels.

The endocannabinoid levels will be studied (baseline and after stimulation) in:

• Normal-weight subjects
• Obese subjects before and after gastric bypass surgery
• Obese subjects before and after a lifestyle intervention

• Study Type: Observational
• Enrollment (Actual): 44

Contacts and Locations

Study Locations

• France
  • Pessac, France, 33600
    • Haut Lévêque Hospital, Endocrine department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

2 groups : from primary care clinic

• obese patients with gastric bypass
• obese patients with lifestyle intervention 1 group : volunteer

Description

Inclusion Criteria:

• Arms 1 and 2:
• Age between 18 and 60
• BMI > 40kg/m² or at least 30kg/m² with complication
• Medical follow up before surgery
• Patients that engaged themselves to a long medical follow up
• Efficient contraception
• Written, informed consent of each subject before the beginning of the study
• Arm 3:
• Age between 18 and 60
• BMI between 18 and 25 kg/m²
• Stable weight over the 3 past months
• Restrain score <4 disinhibition <6and hunger > 4 at the TFEQ
• No job in the endocrinology department
• Written, informed consent of each subject before the beginning of the study

Exclusion Criteria:

• Arms 1,2 and 3
• No care of obesity before inclusion
• Incapacity of the patient to follow a medical follow up
• Drug or alcohol abuse
• Urine test result positive for THC
• Threaten life diseases
• Pregnancy, breast feeding
• Smoking

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Bypass gastric; First arm is represented by obese patients that will be studied before and after a gastric bypass. They will be studied before surgery as well as 1 month and 6 months after surgery.	Biological: Evaluation of the endocannabinoid system; The evaluation of the endocannabinoid system consist in the determination of plasma concentration of the 2 main endocannabinoids (2AG and AEA) before (5 blood samples) and after (5 blood samples) after consumption of a calibrated food. As a comparator, ghrelin will be measured at the same time.; Procedure: Biopsy of visceral and peripheral adipose tissue; The endocannabinoids will be also determined in adipose tissue. Biopsy of visceral and peripheral adipose tissue will be done during surgery and peripheral adipose tissue will be done 6 months after surgery.; Biological: Evaluation of metabolic parameters; The evaluation of the metabolic status consist in evaluation of body composition (DEXA), determination of visceral adiposity (CT scan) and measurement of plasma lipids, glucose, insulin, leptin, adiponectin.; Behavioral: Evolution of behavioral parameters; The behavioral evaluation will de done with different questionnaires: ORWELL 97, HAD scale, Three Factor Eating Questionnaire, Beck Depression inventory, Questionnaire of personality TCI.; Behavioral: Dietician consultation; The evaluation of the metabolic status will also be seen by a dietician.; Behavioral: Psychologist consultation; The behavioural evaluation will de done with a psychologist consultation
Lifestyle intervention; The second group is represented by obese patients that will be studied before lifestyle intervention, 6 months after the beginning of the intervention and after a time that will allow patients to lose the same amount of weight that patients that had been through surgery had lost one month after surgery.	Biological: Evaluation of the endocannabinoid system; The evaluation of the endocannabinoid system consist in the determination of plasma concentration of the 2 main endocannabinoids (2AG and AEA) before (5 blood samples) and after (5 blood samples) after consumption of a calibrated food. As a comparator, ghrelin will be measured at the same time.; Biological: Evaluation of metabolic parameters; The evaluation of the metabolic status consist in evaluation of body composition (DEXA), determination of visceral adiposity (CT scan) and measurement of plasma lipids, glucose, insulin, leptin, adiponectin.; Behavioral: Evolution of behavioral parameters; The behavioral evaluation will de done with different questionnaires: ORWELL 97, HAD scale, Three Factor Eating Questionnaire, Beck Depression inventory, Questionnaire of personality TCI.; Behavioral: Dietician consultation; The evaluation of the metabolic status will also be seen by a dietician.; Behavioral: Psychologist consultation; The behavioural evaluation will de done with a psychologist consultation
Control subjects; The third group is a control group of normal weight people that will be studied at one time and after 6 months with stable weight.	Biological: Evaluation of the endocannabinoid system; The evaluation of the endocannabinoid system consist in the determination of plasma concentration of the 2 main endocannabinoids (2AG and AEA) before (5 blood samples) and after (5 blood samples) after consumption of a calibrated food. As a comparator, ghrelin will be measured at the same time.; Biological: Evaluation of metabolic parameters; The evaluation of the metabolic status consist in evaluation of body composition (DEXA), determination of visceral adiposity (CT scan) and measurement of plasma lipids, glucose, insulin, leptin, adiponectin.; Behavioral: Evolution of behavioral parameters; The behavioral evaluation will de done with different questionnaires: ORWELL 97, HAD scale, Three Factor Eating Questionnaire, Beck Depression inventory, Questionnaire of personality TCI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasmatic endocannabinoïd concentration variation	Inclusion and 6 month-follow up

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma concentration of the endocannabinoids during food exposure	At each visit
Post prandial pic of the plasma concentration of the endocannabinoids	At each visit
Adipose tissue concentration of the endocannabinoids	Inclusion and 6 month-follow up
Plasma concentration of adipokines	At each visit
Body mass index	At each visit
Body composition	At each visit
Insulin sensitivity	At each visit
Area under the curve of plasma concentration of 2AG	Inclusion and 6 month follow-up
Questionaries scores	At each visit

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Study Chair: Antoine BENARD, MD, University Hospital, Bordeaux, France; Principal Investigator: Blandine GATTA-CHERIFI, MD, University Hospital, Bordeaux, France

Publications and helpful links

General Publications

• Sjostrom L, Narbro K, Sjostrom CD, Karason K, Larsson B, Wedel H, Lystig T, Sullivan M, Bouchard C, Carlsson B, Bengtsson C, Dahlgren S, Gummesson A, Jacobson P, Karlsson J, Lindroos AK, Lonroth H, Naslund I, Olbers T, Stenlof K, Torgerson J, Agren G, Carlsson LM; Swedish Obese Subjects Study. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007 Aug 23;357(8):741-52. doi: 10.1056/NEJMoa066254.
• Di Marzo V, Matias I. Endocannabinoid control of food intake and energy balance. Nat Neurosci. 2005 May;8(5):585-9. doi: 10.1038/nn1457.
• Cota D. CB1 receptors: emerging evidence for central and peripheral mechanisms that regulate energy balance, metabolism, and cardiovascular health. Diabetes Metab Res Rev. 2007 Oct;23(7):507-17. doi: 10.1002/dmrr.764.
• Engeli S, Bohnke J, Feldpausch M, Gorzelniak K, Janke J, Batkai S, Pacher P, Harvey-White J, Luft FC, Sharma AM, Jordan J. Activation of the peripheral endocannabinoid system in human obesity. Diabetes. 2005 Oct;54(10):2838-43. doi: 10.2337/diabetes.54.10.2838.
• Bluher M, Engeli S, Kloting N, Berndt J, Fasshauer M, Batkai S, Pacher P, Schon MR, Jordan J, Stumvoll M. Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity. Diabetes. 2006 Nov;55(11):3053-60. doi: 10.2337/db06-0812.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: October 27, 2009
• First Submitted That Met QC Criteria: October 28, 2009
• First Posted (Estimate): October 29, 2009

Study Record Updates

• Last Update Posted (Actual): October 16, 2018
• Last Update Submitted That Met QC Criteria: October 11, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: bariatric surgery; lifestyle intervention; morbid obesity; endocannabinoids system
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: CHUBX 2008/19