Major Depressive DisordersMARVELNCT02590185
MetAbolism vaRiability of VEnLafaxine
A study testing cocktail probe drugs in people with Major Depressive Disorders, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Major Depressive Disorders
- What is being tested?
- cocktail probe drugs
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 205 participants
- Where
- 2 sitesFrance
- Study dates
- Dec 2015to Apr 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
celia Lloret-Linares, MD contact
France2 sites, 2 recruiting
- Recruiting
Fernand Widal hospital
Paris, 75010
Frank Bellivier, MD PhD, frank.bellivier@inserm.fr
- Recruiting
Lariboisiere hospital
Paris, 75010
celia Lloret-Linares, MD, celia.lloret-linares@aphp.fr
About this study
Official title: Xploring Venlafaxine Pharmacokinetic Variability by a Phenotyping Approach
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
- Being tested
- cocktail probe drugs
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cocktail probe drugsDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: cocktail probe drugs |
What is being measured
The primary outcome is the main question the study is designed to answer.
The CYP2C19 activity
5-hydroxyomeprazole/omeprazole
Measured: 2 hours
The CYP2D6 activity
dextrorphan/dextromethorphan ratio
Measured: 2 hours
The CYP3A4 activity
1-hydroxymidazolam/ midazolam ratio
Measured: 2 hours
The P-gp activity
Fexofenadine AUC based on fexofenadine concentrations
Measured: 2, 3 and 6 hours
Secondary outcomes (8)
Tobacco use
Fagerstrom test
Measured: 20, 40, 70 days
Mood disorder
Measured: 20, 40, 70 days
Anxiety scale Tyrer
Measured: 20, 40, 70 days
QIDS-SR16
Measured: 20, 40, 70 days
Criteria for rating medication trials for antidepressant failure and level of resistance
Measured: 20, 40, 70 days
MARS Score
Measured: 20, 40, 70 days
PRISE-M score
Measured: 20, 40, 70 days
FISBER score
Measured: 20, 40, 70 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2015 (estimated)
- Study startDec 2015
- Primary completionDec 2019 (estimated)
- Study completionApr 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisordersStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 205 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Celia Lloret-Linares, MD, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02590185
- Sponsor's protocol ID
- AOM14562
- Acronym
- MARVEL
- Status last verified
- Feb 2019
- First submitted
- 27 Oct 2015
- Last updated
- 19 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 29115994
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Xploring Venlafaxine Pharmacokinetic Variability by a Phenotyping Approach
- ClinicalTrials.gov ID
- NCT02590185
- Acronym / sponsor ID
- MARVEL / AOM14562
- Conditions
- Major Depressive Disorders
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 205 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Dec 2015
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Apr 2020 (estimated)
- First posted
- 28 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| cocktail probe drugs | Experimental | Drug: 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cocktail probe drugsFor 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 | Drug | cocktail probe drugs |
Primary outcome
The CYP2C19 activity
Time frame: 2 hours
5-hydroxyomeprazole/omeprazole
The CYP2D6 activity
Time frame: 2 hours
dextrorphan/dextromethorphan ratio
The CYP3A4 activity
Time frame: 2 hours
1-hydroxymidazolam/ midazolam ratio
The P-gp activity
Time frame: 2, 3 and 6 hours
Fexofenadine AUC based on fexofenadine concentrations
8 secondary outcomes
Tobacco use
Time frame: 20, 40, 70 days
Mood disorder
Time frame: 20, 40, 70 days
Anxiety scale Tyrer
Time frame: 20, 40, 70 days
QIDS-SR16
Time frame: 20, 40, 70 days
Criteria for rating medication trials for antidepressant failure and level of resistance
Time frame: 20, 40, 70 days
MARS Score
Time frame: 20, 40, 70 days
PRISE-M score
Time frame: 20, 40, 70 days
FISBER score
Time frame: 20, 40, 70 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2019.
- Derived from this study: PubMed 29115994Lloret-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.
Related trials for Major Depressive Disorders
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
celia Lloret-Linares, MD contact
Celia Lloret-Linares, MD principal investigator
APHP
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing cocktail probe drugs in people with Major Depressive Disorders, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact celia Lloret-Linares, MD (celia.lloret-linares@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The CYP2C19 activity (time frame: 2 hours). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02590185, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2019.