Clinical trial NCT00943969: Determinants of Oral Morphine Answer Among Obese Patients Before and After Gastric Bypass
Official title: Determinants of Oral Morphine Answer Among Obese Patients Before and After Gastric Bypass
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obesity
Keywords: obesity
gastric bypass
morphine
pharmacokinetic
absorption
Lead sponsor: Hopital Lariboisière
Sponsor class: OTHER
First posted: 2009-07-22
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

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.


Eligibility criteria: 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

Primary outcomes:
measure: 30mg Oral morphine systemic exposure (AUC 0-24)
timeFrame: Before surgery-7-15 days after surgery- 6 months after surgery
Secondary outcomes:
measure: Morphine and M6G AUC, clearance, Cmax and Tmax
timeFrame: Before surgery-7-15 days after surgery- 6 months after surgery
measure: fat mass and total body water (assessed by DEXA and BIA)
timeFrame: before surgery and 6 months following surgery
measure: mRNA and protein expression of P-gp , UGT2B7, MRP2 and MRP3 in intestinal biopsies
timeFrame: obtained from the bariatric surgery
measure: 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
timeFrame: Before surgery
Other outcomes:
Locations:
city: Paris cedex 10
country: France
facility: Unit of Therapeutic Research, Department of Internal Medicine, Lariboisière Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Célia LLoret Linares
role: PRINCIPAL_INVESTIGATOR
References: