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Drug Metabolism and Antidepressant

Cocktail Phenotypic Approach to Explore Antidepressant Pharmacokinetic Variability: a Pilot Study

Status
UNKNOWN
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02438072
Acronym
METADEP
Enrollment
100
Registered
2015-05-08
Start date
2014-12-31
Completion date
2015-12-31
Last updated
2015-05-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Depression

Keywords

antidepressive agent, drug metabolism, CYP450, P-glycoprotein, Phenotypic study

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

Interventions

DRUGOmeprazole (10 mg, A02BC01)

The cocktail of drug substrates will be given one time, one day during the study, to explore the activity of CYP 1A2, 2B6, 2C9, 2C19, 3A4, 2D6, and the P-gp

Sponsors

University Hospital, Geneva
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
P-gp activity>two, three and six hours after an oral intake of the cocktail probe drugsLimited sampling fexofenadine AUC
CYP2C9 activity>two hours after an oral intake of the cocktail probe drugs4-hydroxyflurbiprofen/ flurbiprofen
CYP2C19 activity>two, three and six hours after an oral intake of the cocktail probe drugs5-hydroxyomeprazole/ omeprazole
CYP3A4 activity>two hours after an oral intake of the cocktail probe drugs1-hydroxymidazolam/ midazolam
CYP1A2 activity>two hours after an oral intake of the cocktail probe drugsparaxanthine/caffeine
CYP2B6 activity>two hours after an oral intake of the cocktail probe drugs4-hydroxybupropion/ bupropion
CYP2D6 activity>two hours after an oral intake of the cocktail probe drugsdextrorphan / dextromethorphan

Secondary

MeasureTime frameDescription
Antidepressant tolerancealmost 6 weeks after the last treatment changeFISBER test
Antidepressant efficacyalmost 6 weeks after the last treatment changeTests: MADRS, Hamilton, QIDS-16
Antidepressant Concentrationalmost 6 weeks after the last treatment change

Countries

Switzerland

Contacts

Primary ContactCelia Lloret-Linares, MD, PhD
Celia.LloretLinares@hcuge.ch0041 79 55 36 389

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 24, 2026