Drug Metabolism and Antidepressant

NCT02438072 | Unknown

• 1 other identifier: CER-14051
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression

Keywords

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

Outcome Measures

Primary Outcomes (7)

• CYP1A2 activity

  paraxanthine/caffeine

  >two hours after an oral intake of the cocktail probe drugs

• CYP2B6 activity

  4-hydroxybupropion/ bupropion

  >two hours after an oral intake of the cocktail probe drugs

• CYP2D6 activity

  dextrorphan / dextromethorphan

  >two hours after an oral intake of the cocktail probe drugs

• CYP2C9 activity

  4-hydroxyflurbiprofen/ flurbiprofen

  >two hours after an oral intake of the cocktail probe drugs

• CYP2C19 activity

  5-hydroxyomeprazole/ omeprazole

  >two, three and six hours after an oral intake of the cocktail probe drugs

• CYP3A4 activity

  1-hydroxymidazolam/ midazolam

  >two hours after an oral intake of the cocktail probe drugs

• P-gp activity

  Limited sampling fexofenadine AUC

  >two, three and six hours after an oral intake of the cocktail probe drugs

Secondary Outcomes (3)

• Antidepressant Concentration

  almost 6 weeks after the last treatment change

• Antidepressant tolerance

  almost 6 weeks after the last treatment change

• Antidepressant efficacy

  almost 6 weeks after the last treatment change

Study Arms (1)

Overall population

OTHER

Drug: Omeprazole (10 mg, A02BC01)

Interventions

Omeprazole (10 mg, A02BC01) DRUG

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

Also known as: Flurbiprofen (10 mg, M01AE09), Dextromethorphan (10 mg, R05DA09), Midazolam (1 mg, N05CD08), Fexofenadine (25mg, R06AX26 ), Bupropion (20 mg, N06AX12), Caffeine (50 mg, N06BC01)

Overall population

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Male and female aged from 18 to 70 years
• Volunteers to participate to the study
• Understanding of French language and able to give a written inform consent.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Geneva: lead

Study Sites (1)

Hôpitaux Universitaires de Genève

Geneva, 1205, Switzerland

RECRUITING

Related Publications (3)

• Bosilkovska M, Samer CF, Deglon J, Rebsamen M, Staub C, Dayer P, Walder B, Desmeules JA, Daali Y. Geneva cocktail for cytochrome p450 and P-glycoprotein activity assessment using dried blood spots. Clin Pharmacol Ther. 2014 Sep;96(3):349-59. doi: 10.1038/clpt.2014.83. Epub 2014 Apr 10.

  PMID: 24722393 BACKGROUND

• Hall-Flavin DK, Winner JG, Allen JD, Carhart JM, Proctor B, Snyder KA, Drews MS, Eisterhold LL, Geske J, Mrazek DA. Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting. Pharmacogenet Genomics. 2013 Oct;23(10):535-48. doi: 10.1097/FPC.0b013e3283649b9a.

  PMID: 24018772 RESULT

• Lloret-Linares C, Bosilkovska M, Daali Y, Gex-Fabry M, Heron K, Bancila V, Michalopoulos G, Perroud N, Richard-Lepouriel H, Aubry JM, Desmeules J, Besson M. Phenotypic Assessment of Drug Metabolic Pathways and P-Glycoprotein in Patients Treated With Antidepressants in an Ambulatory Setting. J Clin Psychiatry. 2018 Mar/Apr;79(2):16m11387. doi: 10.4088/JCP.16m11387.

  PMID: 29570971 DERIVED

MeSH Terms

Conditions

Depression

Interventions

Omeprazole; Flurbiprofen; Dextromethorphan; Midazolam; fexofenadine; Bupropion; Caffeine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Propionates; Acids, Acyclic; Carboxylic Acids; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Benzodiazepines; Benzazepines; Propiophenones; Ketones; Xanthines; Purinones; Purines

Study Officials

• Celia Lloret-Linares, MD, PhD

  University Hospital, Geneva

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Celia Lloret-Linares, MD, PhD

CONTACT

0041 79 55 36 389; Celia.LloretLinares@hcuge.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: April 30, 2015
• First Posted: May 8, 2015
• Study Start: December 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: May 8, 2015

Record last verified: 2015-05

Locations

CH (1)