Drug ResistanceM4PNCT03114098
Pharmacogenetics Anomaly Research in Children and Adolescents With Pharmacological Resistance to Psychotropic Drugs
A study testing gene abnormalities in people with Drug Resistance and Psychotropic Drugs, run by Fondation Lenval at 1 site in France.
Trial summary
Psychotropic drugs are frequently used in children and adolescents in France with a prescription rate of 2.5%. Antipsychotics (PA) and antidepressants (AD), each concern 0.3% of the pediatric population (Kovess et al., 2015). Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Drug Resistance, Psychotropic Drugs
- What is being tested?
- gene abnormalities
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteFrance
- Study dates
- 7 Dec 2016to 31 Jan 2019
- 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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Pharmaco resistance to psychotropic drugs
- Obtaining the informed consent of the patient and his / her parents or legal guardian
- Affiliation to a social security system
Who cannot join
- Patient deprived of liberty
Trial locations and contacts
1 site in 1 country.
France1 site
Fondation Lenval Hôpitaux Pédiatriques de Nice CHU-LENVAL
Nice, 06200
About this study
Official title: Personalized Medicine: Pharmacogenetics Anomaly Research in Children and Adolescents With Pharmacological Resistance to Psychotropic Drugs
Psychotropic drugs are frequently used in children and adolescents in France with a prescription rate of 2.5%. Antipsychotics (PA) and antidepressants (AD), each concern 0.3% of the pediatric population (Kovess et al., 2015). Despite appropriate pharmacological treatment, some patients are drug-resistant and have persisting symptoms and ineffective psychotropic treatments. These children and adolescents are generally exposed to many psychotropic molecules and often to poly-therapy.
Most psychotropic treatments, especially AP and AD, are metabolised at the hepatic level by cytochrome P450 and in particular by CYP2D6. Duplication / multiplication of the CYP2D6 gene induces too rapid metabolism of drugs.
Demonstration of a CYP2D6 abnormality has a direct impact on the management of the patient and on the clinical decisions of the clinician. Thus, knowledge of individual metabolism will decrease the failure of treatment, improve quality of life and therapeutic compliance.
Read the detailed description
Psychotropic drugs are frequently used in children and adolescents in France with a prescription rate of 2.5%. Antipsychotics (PA) and antidepressants (AD) each concern 0.3% of the pediatric population (Kovess et al., 2015). Despite appropriate pharmacological treatment, some patients are drug-resistant and have persisting symptoms and ineffective psychotropic treatments. These children and adolescents are generally exposed to many psychotropic molecules and often to poly-therapy. Additionally, hospitalizations for child psychiatry, sometimes of prolonged duration, are frequent for these patients. In France, to date, the psychiatrist practitioner rarely uses pharmacogenetic evaluation as a complementary tool for prescribing psychotropic drugs. Nevertheless, an individualized prescription taking into consideration the patient's individual metabolism could greatly improve the benefit and reduce the risk of psychotropic treatments in the pediatric population.
Most psychotropic treatments, especially AP and AD, are metabolised at the hepatic level by cytochrome P450 and in particular by CYP2D6. Duplication / multiplication of the CYP2D6 gene induces too rapid metabolism of the drugs (ultrafast metabolizer). It is linked to a clinical inefficiency of treatments, and concerns up to 10% of the general population in southern Europe (Scordo et al., 2004).
In a preliminary study in Nice, an abnormality of CYP2D6 was found in 4 of the 7 patients tested with drug-resistant and / or with numerous adverse effects to the AP, of which 3 of the 5 pharmacologically resistant patients shows a duplication of the gene.
Demonstration of a CYP2D6 abnormality has a direct impact on the management of the patient and on the clinical decisions of the clinician. Thus, knowledge of individual metabolism will decrease the failure of treatment, improve quality of life and therapeutic compliance.
- Conditions
- Drug Resistance, Psychotropic Drugs
- Being tested
- gene abnormalities
- Keywords
- Drug Resistance, CYP2D6, cytochrom P450
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gene abnormalitiesOther
A salivary sample (2 ml sample) Blood sampling will be performed to assess treatment tolerance (6 ml)
| Study group | Role | What they receive |
|---|---|---|
| CYP2D6 gene abnormalities | Experimental | * A salivary sample (2 ml sample) which will allow the investigation of an anomaly of the metabolism of psychotropic drug.
* Blood sampling will be performed to assess treatment tolerance (6 ml). A sample (4 ml) will be kept for possible future analyzes in relation to the objectives of this study for the recruiting center of Nice.
* Electrocardiogram
* Clinical exam
* Clinical Global Impression Scale (CGI-S)
* Children's Global Assessment Scale (CGAS)
* Sheehan Disability Scale (SDS)
* Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III )
* Wechsler Intelligence Scale for Children - 4 (WISC-4)
* Wechsler Adult Intelligence Scale 4 (WAIS 4)
* Diagnostic and Statistical Manual of Mental Disorders (DSM)
* Autism Diagnostic Interview (ADI) Receives: Other: gene abnormalities |
What is being measured
The primary outcome is the main question the study is designed to answer.
prevalence of a CYP2D6 duplication or polymorphisms
study the prevalence of a CYP2D6 duplication or polymorphisms associated with an ultrafast metabolizing phenotype in a population of children and adolescents who are drug-resistant to antipsychotic and antidepressant psychotropic drugs. performed by analysis of salivar sample
Measured: At baseline
Secondary outcomes (7)
Psychiatric diagnosis and comorbidities
Diagnostic and Statistical Manual of Mental Disorders 5 DSM5
Measured: At baseline
Global Severity of illness
Clinical Global Impression scale (échelle CGI-I)
Measured: At baseline
Severity of illness for children
Children's Global Assessment Scale (CGAS)
Measured: At baseline
Current and previous psychotropic treatment
Number of different molecules (antipsychotic antidepressant) used during the therapeutic history of the patient, duration of treatment with each molecule, type and maximum dose of current and previous psychotropic treatments.
Measured: At baseline
Side effects in different psychotropic treatments
Type and severity of the adverse effects identified during the various psychotropic treatments will be collected. This collection will be carried out through the interrogation and study of the medical file
Measured: At baseline
New anomalies of CYP2D6 gene
To look for any other abnormality of the CYP2D6 gene not known to be associated with an ultrafast metabolizing phenotype
Measured: At baseline
Description of the clinical phenotype of patients
The characterization of the clinical phenotype will be carried out on the one hand by the standardized diagnostic interview MINI Mini International Neuropsychiatric Interview
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2017
- Study start7 Dec 2016
- Primary completion12 Dec 2018
- Study completion31 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug ResistanceStudies of the same condition, open and under way.
- 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondation Lenval
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Susanne THÜMMLER, MD, Principal investigator, Fondation Lenval Hôpitaux Pédiatriques de Nice CHU-LENVAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03114098
- Sponsor's protocol ID
- 16-HPNCL-02
- Acronym
- M4P
- Status last verified
- Jul 2018
- First submitted
- 22 Feb 2017
- Last updated
- 26 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Personalized Medicine: Pharmacogenetics Anomaly Research in Children and Adolescents With Pharmacological Resistance to Psychotropic Drugs
- ClinicalTrials.gov ID
- NCT03114098
- Acronym / sponsor ID
- M4P / 16-HPNCL-02
- Conditions
- Drug Resistance, Psychotropic Drugs
- Keywords
- Drug Resistance, CYP2D6, cytochrom P450
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Fondation LenvalUniversity, hospital or other
- Study start
- 7 Dec 2016 (actual)
- Primary completion
- 12 Dec 2018 (actual)
- Study completion
- 31 Jan 2019 (actual)
- First posted
- 14 Apr 2017 (actual)
- 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.
Psychotropic drugs are frequently used in children and adolescents in France with a prescription rate of 2.5%. Antipsychotics (PA) and antidepressants (AD), each concern 0.3% of the pediatric population (Kovess et al., 2015). Despite appropriate pharmacological treatment, some patients are drug-resistant and have persisting symptoms and ineffective psychotropic treatments. These children and adolescents are generally exposed to many psychotropic molecules and often to poly-therapy.
Most psychotropic treatments, especially AP and AD, are metabolised at the hepatic level by cytochrome P450 and in particular by CYP2D6. Duplication / multiplication of the CYP2D6 gene induces too rapid metabolism of drugs.
Demonstration of a CYP2D6 abnormality has a direct impact on the management of the patient and on the clinical decisions of the clinician. Thus, knowledge of individual metabolism will decrease the failure of treatment, improve quality of life and therapeutic compliance.
Detailed description
Psychotropic drugs are frequently used in children and adolescents in France with a prescription rate of 2.5%. Antipsychotics (PA) and antidepressants (AD) each concern 0.3% of the pediatric population (Kovess et al., 2015). Despite appropriate pharmacological treatment, some patients are drug-resistant and have persisting symptoms and ineffective psychotropic treatments. These children and adolescents are generally exposed to many psychotropic molecules and often to poly-therapy. Additionally, hospitalizations for child psychiatry, sometimes of prolonged duration, are frequent for these patients. In France, to date, the psychiatrist practitioner rarely uses pharmacogenetic evaluation as a complementary tool for prescribing psychotropic drugs. Nevertheless, an individualized prescription taking into consideration the patient's individual metabolism could greatly improve the benefit and reduce the risk of psychotropic treatments in the pediatric population.
Most psychotropic treatments, especially AP and AD, are metabolised at the hepatic level by cytochrome P450 and in particular by CYP2D6. Duplication / multiplication of the CYP2D6 gene induces too rapid metabolism of the drugs (ultrafast metabolizer). It is linked to a clinical inefficiency of treatments, and concerns up to 10% of the general population in southern Europe (Scordo et al., 2004).
In a preliminary study in Nice, an abnormality of CYP2D6 was found in 4 of the 7 patients tested with drug-resistant and / or with numerous adverse effects to the AP, of which 3 of the 5 pharmacologically resistant patients shows a duplication of the gene.
Demonstration of a CYP2D6 abnormality has a direct impact on the management of the patient and on the clinical decisions of the clinician. Thus, knowledge of individual metabolism will decrease the failure of treatment, improve quality of life and therapeutic compliance.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CYP2D6 gene abnormalities | Experimental | Other: gene abnormalities* A salivary sample (2 ml sample) which will allow the investigation of an anomaly of the metabolism of psychotropic drug. * Blood sampling will be performed to assess treatment tolerance (6 ml). A sample (4 ml) will be kept for possible future analyzes in relation to the objectives of this study for the recruiting center of Nice. * Electrocardiogram * Clinical exam * Clinical Global Impression Scale (CGI-S) * Children's Global Assessment Scale (CGAS) * Sheehan Disability Scale (SDS) * Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III ) * Wechsler Intelligence Scale for Children - 4 (WISC-4) * Wechsler Adult Intelligence Scale 4 (WAIS 4) * Diagnostic and Statistical Manual of Mental Disorders (DSM) * Autism Diagnostic Interview (ADI) |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Pharmaco resistance to psychotropic drugs
- Obtaining the informed consent of the patient and his / her parents or legal guardian
- Affiliation to a social security system
Key exclusion criteria (1 listed)
- Patient deprived of liberty
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 |
|---|---|---|
| gene abnormalitiesA salivary sample (2 ml sample) Blood sampling will be performed to assess treatment tolerance (6 ml) | Other | CYP2D6 gene abnormalities |
Primary outcome
prevalence of a CYP2D6 duplication or polymorphisms
Time frame: At baseline
study the prevalence of a CYP2D6 duplication or polymorphisms associated with an ultrafast metabolizing phenotype in a population of children and adolescents who are drug-resistant to antipsychotic and antidepressant psychotropic drugs. performed by analysis of salivar sample
7 secondary outcomes
Psychiatric diagnosis and comorbidities
Time frame: At baseline
Global Severity of illness
Time frame: At baseline
Severity of illness for children
Time frame: At baseline
Current and previous psychotropic treatment
Time frame: At baseline
Side effects in different psychotropic treatments
Time frame: At baseline
New anomalies of CYP2D6 gene
Time frame: At baseline
Description of the clinical phenotype of patients
Time frame: At baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2019.
- Individual participant dataSharing planned: No
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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.
Susanne THÜMMLER, MD principal investigator
Fondation Lenval Hôpitaux Pédiatriques de Nice CHU-LENVAL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing gene abnormalities in people with Drug Resistance and Psychotropic Drugs, run by Fondation Lenval at 1 site 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 3 inclusion and 1 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: finished, as of the sponsor's last update on 26 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 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
prevalence of a CYP2D6 duplication or polymorphisms (time frame: At baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Feb 2019.