MetAbolism vaRiability of VEnLafaxine

Major Depressive Disorders Clinical Trial

— MARVEL  

Official title:

Xploring Venlafaxine Pharmacokinetic Variability by a Phenotyping Approach

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02590185
• Other study ID #: AOM14562
• Status: Recruiting
• Phase: N/A
• Start date: December 2015
• Est. completion date: April 2020

Study information

• Verified date: February 2019
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: celia Lloret-Linares, MD
• Email: celia.lloret-linares[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 205
• Est. completion date: April 2020
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorders

Intervention

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

Locations

Country	Name	City	State
France	Fernand Widal hospital	Paris
France	Lariboisiere hospital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The CYP2C19 activity	5-hydroxyomeprazole/omeprazole	2 hours
Primary	The CYP2D6 activity	dextrorphan/dextromethorphan ratio	2 hours
Primary	The CYP3A4 activity	1-hydroxymidazolam/ midazolam ratio	2 hours
Primary	The P-gp activity	Fexofenadine AUC based on fexofenadine concentrations	2, 3 and 6 hours
Secondary	Tobacco use	Fagerstrom test	20, 40, 70 days
Secondary	Mood disorder		20, 40, 70 days
Secondary	Anxiety scale Tyrer		20, 40, 70 days
Secondary	QIDS-SR16		20, 40, 70 days
Secondary	Criteria for rating medication trials for antidepressant failure and level of resistance		20, 40, 70 days
Secondary	MARS Score		20, 40, 70 days
Secondary	PRISE-M score		20, 40, 70 days
Secondary	FISBER score		20, 40, 70 days