Clinical trial NCT01003873: Gastric Bypass and Peripheral Activity of the Endocannabinoid System
Official title: Effect of Weight Loss Induced Either by Gastric Bypass or Lifestyle Intervention on the Peripheral Activity of the Endocannabinoid System
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity
Keywords: morbid obesity
bariatric surgery
lifestyle intervention
endocannabinoids system
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2009-10-29
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

Brief summary: 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

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

Eligibility criteria: 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

Primary outcomes:
measure: Plasmatic endocannabinoïd concentration variation
timeFrame: Inclusion and 6 month-follow up
Secondary outcomes:
measure: Plasma concentration of the endocannabinoids during food exposure
timeFrame: At each visit
measure: Post prandial pic of the plasma concentration of the endocannabinoids
timeFrame: At each visit
measure: Adipose tissue concentration of the endocannabinoids
timeFrame: Inclusion and 6 month-follow up
measure: Plasma concentration of adipokines
timeFrame: At each visit
measure: Body mass index
timeFrame: At each visit
measure: Body composition
timeFrame: At each visit
measure: Insulin sensitivity
timeFrame: At each visit
measure: Area under the curve of plasma concentration of 2AG
timeFrame: Inclusion and 6 month follow-up
measure: Questionaries scores
timeFrame: At each visit
Other outcomes:
Locations:
city: Pessac
country: France
facility: Haut Lévêque Hospital, Endocrine department
Study officials:
affiliation: University Hospital, Bordeaux, France
name: Blandine GATTA-CHERIFI, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Bordeaux, France
name: Antoine BENARD, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.