MARVEL: MetAbolism vaRiability of VEnLafaxine

• Sponsor: Assistance Publique - Hôpitaux de Paris (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT02590185
• Collaborator: (none)
• Enrollment: 205
• Locations: 2
• Arm: 1
• Duration (Months): 52
• Patients Per Site: 102.5
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

Regarding the direct costs and the social value of depression, the decision of an antidepressant treatment prescription must be optimized as much as possible. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence burden and costs of affective disorders.

There is hope that biomarkers will be found to guide treatment selection. It might be of decisive interest to be able to assess an individual's metabolism activity. We propose here to explore the relationship between the activity of drug-metabolizing enzymes (DME) and transporters- assessed by a phenotypic approach and the efficacy of antidepressants. We will focus on venlafaxine (V) that provides a reasonable second-step choice for patients with depression and is used extensively in psychiatric practice, and the metabolism of which involves several cytochromes (CYP) P450 enzymes and the transporter P-gp.

Thus, the primary objective of this study is to study the correlation between the concentration of V and its metabolite ODesmethylV (V+ODV) and drug metabolism variability assessed by a phenotypic approach, in patients with major depressive disorder and MADRS ≥ 20 despite 4 weeks of V at 150mg or less

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorders	Drug: cocktail probe drugs	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 205 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Xploring Venlafaxine Pharmacokinetic Variability by a Phenotyping Approach
• Study Start Date: Dec 1, 2015
• Anticipated Primary Completion Date: Dec 1, 2019
• Anticipated Study Completion Date: Apr 1, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: cocktail probe drugs A capsule of omeprazole ABBOTT® 10mg 10 mg of an oral liquid formulation of Dextrométhorphane bromhydrate (Drill Pierre FABRE MEDICAMENT® 5mg/5mL, syrup) 1 mg of an injectable solution of Midazolam for oral administration (Midazolam Panpharma® 1mg/mL, injectable solution) A tablet of fexofenadine Zentiva® 120mg

Drug: cocktail probe drugs; For the assessment of drug-metabolizing enzyme activity, the patients will be given the cocktail probe drugs, by oral route, one time during the study: A capsule of omeprazole ABBOTT® 10mg 10 mg of an oral liquid formulation of Dextrométhorphane bromhydrate (Drill Pierre FABRE MEDICAMENT® 5mg/5mL, syrup) 1 mg of an injectable solution of Midazolam for oral administration (Midazolam Panpharma® 1mg/mL, injectable solution) A tablet of fexofenadine Zentiva® 120mg

Outcome Measures

Primary Outcome Measures

1. The CYP2C19 activity [2 hours]

   5-hydroxyomeprazole/omeprazole

2. The CYP2D6 activity [2 hours]

   dextrorphan/dextromethorphan ratio

3. The CYP3A4 activity [2 hours]

   1-hydroxymidazolam/ midazolam ratio

4. The P-gp activity [2, 3 and 6 hours]

   Fexofenadine AUC based on fexofenadine concentrations

Secondary Outcome Measures

1. Tobacco use [20, 40, 70 days]

   Fagerstrom test

2. Mood disorder [20, 40, 70 days]

3. Anxiety scale Tyrer [20, 40, 70 days]

4. QIDS-SR16 [20, 40, 70 days]

5. Criteria for rating medication trials for antidepressant failure and level of resistance [20, 40, 70 days]

6. MARS Score [20, 40, 70 days]

7. PRISE-M score [20, 40, 70 days]

8. FISBER score [20, 40, 70 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient (Hospitalized or outpatient) with major depressive disorder and MADRS ≥ 20 at visit of selection

• Patients non responders to V after 4 weeks of V at 150mg or less

• Decision of the psychiatrist to increase the dose of V at visit of selection

• Understanding of French language and able to give a written inform consent.

• Informed consent signed to participate to the study

• Individuals covered by social security regimen

Exclusion Criteria:

• Patients treated by more than one antidepressant

• Patients currently treated with one of the drug substrate of the cocktail

• Sensitivity or contra-indication to any of the substrate drugs used

• Current pregnancy, desire to get pregnant, or breastfeeding

• Bipolar disorder and schizophrenia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fernand Widal hospital	Paris		France	75010
2	Lariboisiere hospital	Paris		France	75010

Sponsors and Collaborators

• Assistance Publique - Hôpitaux de Paris

Investigators

• Principal Investigator: Celia Lloret-Linares, MD, APHP

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT02590185
• Other Study ID Numbers: AOM14562
• First Posted: Oct 28, 2015
• Last Update Posted: Feb 19, 2019
• Last Verified: Feb 1, 2019

• Additional relevant MeSH terms: Depressive Disorder; Depressive Disorder, Major

Study Results

No Results Posted as of Feb 19, 2019