Determinants of Oral Morphine Answer Among Obese Patients Before and After Gastric Bypass

Phase 4

Completed

• Conditions: Obesity
• Interventions: Procedure: gastric bypass

• Registration Number: NCT00943969
• Lead Sponsor: Hopital Lariboisière

Brief Summary

The bariatric surgery is widely used to treat obesity. Roux-en-Y gastric bypass is one of the most frequently surgical methods performed and combines restrictive and malabsorptive procedures. Different data suggest that this surgery may modify drug absorption and we think it would be clinically relevant to describe the consequences of gastric bypass on drug systemic exposure in obese patients, since no data on the comparison between the pharmacokinetics (PK) of a drug before and after surgery are available and help to predict the drugs posology.The investigators decided to study the morphine because there is a lack of information about the PK, pharmacodynamics (PD) et pharmacogenetics (PG) of morphine in obese subjects, in contrary with anaesthetic drugs. This is a drug with a narrow therapeutic range frequently prescribed in obese patients.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-04
• Primary Completion: 2009-05
• Study First Submitted: 2009-07-21
• Study First Submitted QC: 2009-07-21
• Study First Posted: 2009-07-22
• Study Completion: 2010-01
• Status Verified: 2015-12
• Last Update Submitted: 2015-12-14
• Last Update Posted: 2015-12-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

Inclusion Criteria

• Patients aged between 18 and 60 years old.
• Patients with morbid obesity (IMC > 40 kg/m²) or severe obesity (IMC=35-40 kg/m²) with co morbidities (sleep apnea syndrome or hypertension or steatosis hepatitis) with a favourable decision of a multidisciplinary team for a gastric bypass.
• Patient agreeing to go 3 times for a one day hospitalisation in the URT of the Lariboisière Hospital for the morphine PK/PD.
• Patient with a previous medical examination.
• Patient giving its well-informed and free consent after information.

Exclusion Criteria

• diabetes
• concomitant sedative, antidepressive or analgesic treatments or drugs unadvised with morphine
• untreated sleep apnea syndrom, hypoxia (PaO2<70mmHg) or hypercapnia (PaCO2>45mmHg), anaemia <10g/dL, ASAT or ALAT>3N

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
obemo	gastric bypass	-

Primary Outcome Measures

Name	Time	Method
30mg Oral morphine systemic exposure (AUC 0-24)	Before surgery-7-15 days after surgery- 6 months after surgery

Secondary Outcome Measures

Name	Time	Method
Morphine and M6G AUC, clearance, Cmax and Tmax	Before surgery-7-15 days after surgery- 6 months after surgery
fat mass and total body water (assessed by DEXA and BIA)	before surgery and 6 months following surgery
genetic polymorphisms known to affect expression and/or activity of enzymes, receptors and transporters involved in morphine PK/PD (UGT2B7, P-gp, OPRM1, COMT) and morphine PK/PD	Before surgery
mRNA and protein expression of P-gp , UGT2B7, MRP2 and MRP3 in intestinal biopsies	obtained from the bariatric surgery

Trial Locations

Locations (1)

Unit of Therapeutic Research, Department of Internal Medicine, Lariboisière Hospital; 🇫🇷 Paris cedex 10, France