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

Study Overview
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Brief Summary
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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.

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

Conditions
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Obesity

Intervention / Treatment
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* Procedure: gastric bypass


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: obemo<br> | Procedure: gastric bypass<br>* gastric bypass combines restrictive and malabsorptive procedures<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30mg Oral morphine systemic exposure (AUC 0-24) |  | Before surgery-7-15 days after surgery- 6 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| mRNA and protein expression of P-gp , UGT2B7, MRP2 and MRP3 in intestinal biopsies |  | obtained from the bariatric 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, gastric bypass, morphine, pharmacokinetic, absorption