Pharmacogenetics Anomaly Research in Children and Adolescents With Pharmacological Resistance to Psychotropic Drugs

Drug Resistance Clinical Trial

— M4P  

Official title:

Personalized Medicine: Pharmacogenetics Anomaly Research in Children and Adolescents With Pharmacological Resistance to Psychotropic Drugs

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03114098
• Other study ID #: 16-HPNCL-02
• Status: Completed
• Phase: N/A
• Start date: December 7, 2016
• Est. completion date: January 31, 2019

Study information

• Verified date: July 2018
• Source: Fondation Lenval
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: January 31, 2019
• Est. primary completion date: December 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Patient deprived of liberty

Related Conditions & MeSH terms

• Drug Resistance
• Psychotropic Drugs

Intervention

Other:
• gene abnormalities
A salivary sample (2 ml sample) Blood sampling will be performed to assess treatment tolerance (6 ml)

Locations

Country	Name	City	State
France	Fondation Lenval Hôpitaux Pédiatriques de Nice CHU-LENVAL	Nice

Sponsors (1)

Lead Sponsor	Collaborator
Fondation Lenval

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	At baseline
Secondary	Psychiatric diagnosis and comorbidities	Diagnostic and Statistical Manual of Mental Disorders 5 DSM5	At baseline
Secondary	Global Severity of illness	Clinical Global Impression scale (échelle CGI-I)	At baseline
Secondary	Severity of illness for children	Children's Global Assessment Scale (CGAS)	At baseline
Secondary	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.	At baseline
Secondary	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	At baseline
Secondary	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	At baseline
Secondary	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	At baseline