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.
Aperçu de l'étude
Description détaillée
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.
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
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Paris, France, 75010
- Unit of internal medicine A, Lariboisière Hospital
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La 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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: phenotypical approach
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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
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Phenotypical markers of enzymes and transporter activity
Délai: at 5-8weeks
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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
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at 5-8weeks
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Phenotypical markers of enzymes and transporter activity
Délai: 25-30 weeks
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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
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25-30 weeks
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Intestinal and hepatic expression and activity of the enzymes and transporter of interest and markers of inflammation
Délai: before surgery
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Intestinal and hepatic expression and activity of the enzymes and transporter of interest and markers of inflammation
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before surgery
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Célia LLORET-LINARES, MD,, Assistance Publique - Hôpitaux de Paris
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- P100506
- 2011-A00312-39 (Autre identifiant: IDRCB)
Informations sur les médicaments et les dispositifs, documents d'étude
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