PhaRmacOgenetics and Therapeutic Drug Monitoring In SchizophrEnia

NCT05839613 | Not Yet Recruiting

• 1 other identifier: 2022-A01015-38
• Study Type: interventional
• Target: 400
• Locations: 0 countries
• Sites: N/A

Brief Summary

Schizophrenia is a severe chronic mental disorder with a long-term treatment. Most antipsychotic (AP) drugs are effective for only 30% to 60% of patients and for many drugs, treatment selection remains a "trial-and-error" process.The main result of treatment inefficiency is relapse, the recurrence of acute symptoms after a period of partial or complete remission. Pharmacogenetics (PG) is the study of genetic differences in drug met-abolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects. PG testing could therefore identify patients at potentially high risk of relapse allowing the opportunity of an individualized prescription. In this study, PG was shown to improve the safety profile of AP treatments in patients presenting PM or UM CYP variants, by reducing associated side effects. Therapeutic Drug Monitoring (TDM) is the quantification and interpretation of drug concentration in blood to optimize pharmacotherapy . For drugs with established therapeutic reference ranges (TRR) or with a narrow therapeutic index, it makes sense to measure drug concentrations in blood for dose titration after initial prescription or after dose change. Non adherence is a recurrent problem in the management of schizophrenia, leading to reduced quality of life and increased risk of relapse. TDM is recognized as a direct reliable measure for drug adherence and can be an additional support after a therapy adjustment. Additionally, TDM can be useful to educate patients and make them more aware of their treatment. Finally, TDM is likely to ensure a better tolerance and fewer side effects for APs, while allowing a better efficacy. However, evidence on the clinical impact of this tool in schizophrenic population is lacking and randomized clinical trials are needed to confirm it. Finally, relapses occur frequently in schizophrenia and the cost for a relapsing schizophrenic patient is estimate over 4 times higher than for a non-relapsing patient, highlighting the importance of cost-effective care strategies. When separately used PG testing or TDM alone, might not be sufficient to ensure the clinical utility and cost-effectiveness of these tests. We hypothesize that individualized medicine including the association of PG testing with TDM (PG/TDM intervention), on the most commonly prescribed AP drugs, can reduce relapse rate at one year while being cost-effective.

Conditions

Patients With Schizophrenia

Outcome Measures

Primary Outcomes (5)

• Clinical worsening

  Clinical worsening as defined by CGI-S score ≥ 5 and an increase of 25 % from base- line in the total score of the PANSS or an increase of 10 points if the baseline score was 40 or less Csernansky criteria (Csernansky et al. 2002)

  12 months

• Hospitalization

  Hospitalization due to worsening of psychotic symptoms

  12 months

• Risk of suicide

  Risk of suicide as defined by a CGI-SS score ≥ 6 (much worse)

  12 months

• Violent behavior

  Violent behavior resulting in clinically significant self-injury, injury to another person, or property damage

  12 months

• Serious Adverse Events

  APs related Serious Adverse Events (SAE)

  12 months

Secondary Outcomes (6)

• Number of relapses

  12 months

• Time to relapse

  12 months

• Remission rate

  12 months

• Therapeutic range

  12 months

• Clinical change

  12 months

Study Arms (2)

PG/TDM group

EXPERIMENTAL

experimental group with PG/TDM analysis results avalaible

Diagnostic Test: Therapeutic Drug Monitoring (TDM) and Pharmacogenetics (PG)

blinded group

EXPERIMENTAL

experimental group with PG/TDM analysis results blinded

Diagnostic Test: Therapeutic Drug Monitoring (TDM) and Pharmacogenetics (PG)

Interventions

Therapeutic Drug Monitoring (TDM) and Pharmacogenetics (PG) DIAGNOSTIC_TEST

Pharmacogenetics (PG) is the study of genetic differences in drug met-abolic pathways Therapeutic Drug Monitoring (TDM) is the quantification and interpre-tation of drug concentration in blood to optimize pharmacotherapy

PG/TDM group; blinded group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age ≥18 years and ≤ 60 years.
• Diagnostic of schizophrenia according to DSM-5.
• The clinical situation of the patient justifies a modification of his AP treatment according to the judgment of the attending psychiatrist (relapsing patients or patients in maintenance phase judged clinically stable by the attending psychiatrist but not optimally treated e.g. non- satisfactory treatment regarding symptoms or adverse events (AEs), Gaebel et al. 2010) or non-compliant patient or patient who has stopped the AP treatment.
• The patient is to receive a prescription for at least one of the following molecules in oral or injectable forms: aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, amisulpride
• Women and men of reproductive potential must agree to use highly effective contraception during the study.

You may not qualify if:

• Patients who do not meet the schizophrenia criteria as defined in the DSM-5.
• Patient with current prescription of clozapine.
• Patient who are in maintenance phase and optimally treated e.g. satisfactory treat- ment regarding symptoms or AEs (Gaebel et al. 2010).
• Previous PG testing used for drug therapy adjustment.
• Pregnant or breastfeeding woman.
• Subject refusing to give written informed consent.
• Adults protected by the law
• Subject non-affiliated to the French health insurance.

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

MeSH Terms

Interventions

Drug Monitoring

Intervention Hierarchy (Ancestors)

Monitoring, Physiologic; Diagnostic Techniques and Procedures; Diagnosis

Central Study Contacts

Olivier BLIN, Pr

CONTACT

04 91 38 75 63; olivier.blin@ap-hm.fr

Romain GUILHAUMOU, Dr

CONTACT

04 91 38 75 65; romain.guilhaumou@ap-hm.fr

Study Design

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

Model Details: The design of this study is a two parallel arms, followed during 12 months, randomized (1:1 ratio) as follow: * 200 patients in the experimental group with PG/TDM intervention (PG/TDM group). * 200 patients in Control group with the SOC group.

Study Record Dates

• First Submitted: April 20, 2023
• First Posted: May 3, 2023
• Study Start: May 1, 2023
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: May 3, 2023

Record last verified: 2023-04