Phenotypical Approach of the Drug Metabolizing Hormones Activity Before and After Roux-en Y-Gastric Bypass (SODA)

Phenotypical Approach of the Drug Metabolizing Hormones Activity (CYP1A2, CYP2D6, CYP2C9, CYP2C19, CYP3A4 and P-gp) Before and After Roux-en Y-Gastric Bypass. The SODA Protocol: Surgery for Obesity and Drug Availability

The activity of drug-metabolizing enzymes and transporters evolutes after Roux-en-Y gastric Bypass.

Primary aim : To study the intra individual evolution of phenotypical markers of different drug metabolizing enzymes and one transporter (CYP1A2, CYP2D6, CYP2C9, CYP2C19, CYP3A4 and P-gp), using a cocktail phenotypic approach, after Roux-en-Y gastric Bypass.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: phenotypical approach

Detailed Description

Principal Judgement criteria :

Phenotypical markers of enzymes and transporter activity before, at 5-8 weeks and 25-30 weeks following surgery.

Secondary judgement criteria :

• Genetic polymorphisms known to affect expression and/or activity of enzymes and transporter.
• Intestinal and hepatic expression and activity of the enzymes and transporter of interest.
• Markers of inflammation Methodology, study design : open-labelled monocentric study.

Sample size : It will be a descriptive experimental study involving 12 subjects.

Study design : In centre 1: Inclusion at least 2 weeks prior to surgery (V0)

In centre 2: Three studies of 12 hours each will occur (in addition with the usual clinical and surgical follow up) at three times periods: in the 8 weeks period before surgery (V1), at 5-8 weeks after surgery (V2) and at 25-30 weeks after surgery (V3).

In centre 3: the patients will undergo gastric bypass surgery (corresponding to the usual clinical and surgical follow up) and samples of jejunum and liver will be obtain during the surgery (J0).

Centres 4 and 5 are involved in samples analysis.Hence, patients will attend 3 visits, in addition to the usual clinical and surgical follow-up.

Study duration: 26 months (with duration of inclusion of 18 months)

Duration for a patient: 38 weeks at maximum (8 months)

Investigating center and participating units: one center enrolling the patients and three centers involving in the others investigations.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Unit of internal medicine A, Lariboisière Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with morbid obesity (IMC > 40 kg/m²) or severe obesity (IMC=35-40 kg/m²) with co morbidities (sleep apnea syndrome or hypertension without treatment or steatosis hepatitis) candidates for a gastric bypass.
• Patient not receiving more than two treatments whose effect on the expression of enzymes and drug transporters is zero other than vitamins.
• Patient agreeing to participate at three studies of one day (12 hours) occurring at three different periods.
• Patients aged between 18 and 60 years old.
• Patient giving its well-informed and free consent.
• Patient without allergy to any of the drugs used for test.
• Patients living in France during the study and with French social security

Exclusion Criteria:

• Tabacco
• Contraception including estrogens compounds
• Medication other than vitamins.
• Allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: phenotypical approach	Drug: phenotypical approach; each visit : CAFEINE : (solution orale) 2 ampoules de 2 ml = 100 mg de CAFEINE DEXTROMETHORPHANE : 15 ml de sirop contains 20 mg =>22,5 ml = 30mg Midazolam : (solution injectable, ampoule 1 ml = 1 mg) : deux ampoules = 2 mg Digoxine nativelle (solution injectable, ampoule de 0.5mg) : 1 ampoule per os = 0.5 mg Losartan 50 mg : 1cp de 50mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phenotypical markers of enzymes and transporter activity	plasmatic [Paraxanthine/caffeine] ratio (T4H) at 5-8 weeks following surgery. - plasmatic [Omeprazole/5-hydroxyomeprazole] ratio (T4H) at 5-8 weeks following surgery. - urinary Log (dextromethorphan/dextrorphan) (T0-T8h) at 5-8 weeks following surgery. - urinary Losartan/ E-3174 (T0-8h) at 5-8 weeks following surgery. - plasmatic AUC 0-inf midazolam at 5-8 weeks following surgery. - plasmatic AUC 0-inf digoxin at 5-8 weeks following surgery	at 5-8weeks
Phenotypical markers of enzymes and transporter activity	plasmatic [Paraxanthine/caffeine] ratio (T4H) at 25-30 weeks following surgery. - plasmatic [Omeprazole/5-hydroxyomeprazole] ratio (T4H) at 25-30 weeks following surgery. - urinary Log (dextromethorphan/dextrorphan) (T0-T8h) at 25-30 weeks following surgery. - urinary Losartan/ E-3174 (T0-8h) at 25-30 weeks following surgery. - plasmatic AUC 0-inf midazolam at 25-30 weeks following surgery. - plasmatic AUC 0-inf digoxin at 25-30 weeks following surgery	25-30 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal and hepatic expression and activity of the enzymes and transporter of interest and markers of inflammation	Intestinal and hepatic expression and activity of the enzymes and transporter of interest and markers of inflammation	before surgery

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Ministry of Health, France
• Investigators: Principal Investigator: Célia LLORET-LINARES, MD,, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: August 19, 2011
• First Submitted That Met QC Criteria: September 28, 2011
• First Posted (Estimate): September 29, 2011

Study Record Updates

• Last Update Posted (Estimate): January 4, 2017
• Last Update Submitted That Met QC Criteria: January 3, 2017
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Obesity; drug metabolizing enzymes and drug transporter; Roux-en Y-Gastric Bypass; Drug Availability; BMI over 35kg/m² and comorbidities or >40kg/m²
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: P100506; 2011-A00312-39 (Other Identifier: IDRCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No