Drug Metabolism and Antidepressant

Not Applicable

• Conditions: Depression
• Interventions: Drug: Omeprazole (10 mg, A02BC01)

• Registration Number: NCT02438072
• Lead Sponsor: University Hospital, Geneva

Brief Summary

We propose here to explore systematically the association between drug-metabolizing enzymes activity assessed by a phenotypical approach and antidepressant plasma concentration, efficacy and tolerance in the clinical setting. During one year, patients receiving antidepressant will be included in tis prospective clinical, naturalistic and descriptive pilot study.

Detailed Description

* Objectives To describe drug metabolism variability in depressive patients using a phenotypic approach

* Study design Prospective, clinical, naturalistic, descriptive study During a consultation with their clinician, depressive patients will receive information.

During the visit V0 with an investigator: patients will be included:

* Verification of inclusion and non inclusion criteria

* Reminder participation conditions

* Inclusion, signature of consent

* Collection of clinical and demographic features Between V0 and V1, for patients with change in antidepressant therapy, will take place telephone interviews every two weeks, conducted by the clinician to evaluate treatment depression response (tolerance and efficacy)

During the visit V1, will take place:

* Phenotypic study

* Genetic study

* Dosage of current antidepressant drug

* Clinical evaluation: efficacy and tolerance

* Number of patients During one year, the protocol will be proposed to all patients with depression and decision of change in antidepressant therapy, and all patients with stability od prescription since almost 6 weeks. The inclusion of approximately 100 patients is expected.

* Name of the finished product Zyban®, Froben®, Antra®, Bexine®, Dormicum® Telfast®

* Name of the active substance Omeprazole (10 mg, A02BC01) Caffeine (50 mg, N06BC01) Flurbiprofen (10 mg, M01AE09) Dextromethorphan (10 mg, R05DA09) Midazolam (1 mg, N05CD08) Fexofenadine (25mg, R06AX26 ) Bupropion (20 mg, N06AX12)

* Duration of treatment One time during the study, one day (Visit 1)

* Time plan of research -Duration for the patient: The study will stop when the patient has performed the V1 study Minimal delay between V0 and V1: 6 weeks (5-7 weeks) : for patient with decision to change the treatment, 5 days for patients with stability of treatment since almost 6 weeks.

Maximal delay of participation for the patient: 4 months even when V1 was not performed

-Overall duration of inclusion: one year Maximal overall duration of the study: 12 months+4 months= 16 months Maximal duration for the analytical study since the beginning of the study= 16 months+6 months: 22 months.

Maximal delay for communication of the results: 2 years after the beginning of the study

Study Timeline

• Study Start: 2014-12
• Study First Submitted: 2015-04-30
• Status Verified: 2015-05
• Study First Submitted QC: 2015-05-05
• Last Update Submitted: 2015-05-05
• Study First Posted: 2015-05-08
• Last Update Posted: 2015-05-08
• Primary Completion: 2015-12
• Study Completion: 2015-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Patients with clinical diagnosis of depression and decision to change antidepressant therapy (augmentation or switch) OR Patients with clinical diagnosis of depression and stability of prescription since almost 6 weeks
2. Male and female aged from 18 to 70 years
3. Volunteers to participate to the study
4. Understanding of French language and able to give a written inform consent.

Exclusion Criteria

Renal or hepatic impairment (Clearance below 60mL/min, AST or ALT over 3N) Sensitivity to any of the substrate drugs used ECG showing long QT interval (>0.46sec) No antidepressant dosage available Current pregnancy or desire to get pregnant

Criteria to perform V1 Sufficient compliance between V0 and V1 Six weeks period without change in antidepressant therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Overall population	Omeprazole (10 mg, A02BC01)	-

Primary Outcome Measures

Name	Time	Method
CYP2B6 activity	>two hours after an oral intake of the cocktail probe drugs	4-hydroxybupropion/ bupropion
CYP2D6 activity	>two hours after an oral intake of the cocktail probe drugs	dextrorphan / dextromethorphan
CYP2C9 activity	>two hours after an oral intake of the cocktail probe drugs	4-hydroxyflurbiprofen/ flurbiprofen
CYP2C19 activity	>two, three and six hours after an oral intake of the cocktail probe drugs	5-hydroxyomeprazole/ omeprazole
P-gp activity	>two, three and six hours after an oral intake of the cocktail probe drugs	Limited sampling fexofenadine AUC
CYP1A2 activity	>two hours after an oral intake of the cocktail probe drugs	paraxanthine/caffeine
CYP3A4 activity	>two hours after an oral intake of the cocktail probe drugs	1-hydroxymidazolam/ midazolam

Secondary Outcome Measures

Name	Time	Method
Antidepressant tolerance	almost 6 weeks after the last treatment change	FISBER test
Antidepressant Concentration	almost 6 weeks after the last treatment change
Antidepressant efficacy	almost 6 weeks after the last treatment change	Tests: MADRS, Hamilton, QIDS-16

Trial Locations

Locations (1)

Hôpitaux Universitaires de Genève; 🇨🇭 Genève, Switzerland