MetAbolism vaRiability of VEnLafaxine

NCT02590185 | Unknown

• 1 other identifier: AOM14562
• Study Type: interventional
• Target: 205
• Locations: 1 country
• Sites: 2

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

Conditions

Major Depressive Disorders

Outcome Measures

Primary Outcomes (4)

• The CYP2C19 activity

  5-hydroxyomeprazole/omeprazole

  2 hours

• The CYP2D6 activity

  dextrorphan/dextromethorphan ratio

  2 hours

• The CYP3A4 activity

  1-hydroxymidazolam/ midazolam ratio

  2 hours

• The P-gp activity

  Fexofenadine AUC based on fexofenadine concentrations

  2, 3 and 6 hours

Secondary Outcomes (8)

• Tobacco use

  20, 40, 70 days

• Mood disorder

  20, 40, 70 days

• Anxiety scale Tyrer

  20, 40, 70 days

• QIDS-SR16

  20, 40, 70 days

• Criteria for rating medication trials for antidepressant failure and level of resistance

  20, 40, 70 days

Study Arms (1)

cocktail probe drugs

EXPERIMENTAL

* 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

Interventions

cocktail probe drugs DRUG

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

cocktail probe drugs

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Fernand Widal hospital

Paris, 75010, France

RECRUITING

Lariboisiere hospital

Paris, 75010, France

RECRUITING

Related Publications (1)

• Lloret-Linares C, Daali Y, Chevret S, Nieto I, Moliere F, Courtet P, Galtier F, Richieri RM, Morange S, Llorca PM, El-Hage W, Desmidt T, Haesebaert F, Vignaud P, Holtzmann J, Cracowski JL, Leboyer M, Yrondi A, Calvas F, Yon L, Le Corvoisier P, Doumy O, Heron K, Montange D, Davani S, Deglon J, Besson M, Desmeules J, Haffen E, Bellivier F. Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study). BMC Pharmacol Toxicol. 2017 Nov 7;18(1):70. doi: 10.1186/s40360-017-0173-2.

  PMID: 29115994 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Celia Lloret-Linares, MD

  APHP

  PRINCIPAL INVESTIGATOR

Central Study Contacts

celia Lloret-Linares, MD

CONTACT

celia.lloret-linares@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2015
• First Posted: October 28, 2015
• Study Start: December 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: April 1, 2020
• Last Updated: February 19, 2019

Record last verified: 2019-02

Locations

FR (2)