Risk of Breakthrough Symptoms With Long-Acting Injectable Medications

Schizophrenia Clinical Trial

Official title: Risk of Breakthrough Symptoms On Antipsychotic Maintenance Medication When Remitted Patients Are Treated With Long-Acting Injectable Medications

Status Recruiting

Clinical Trial Summary

This prospective longitudinal cohort study will follow patients with schizophrenia who are treated with second generation long-acting injectable antipsychotic medications (LAIs) for 48 weeks to determine the risk of psychotic symptom relapse when treatment adherence is established. The study is designed to minimize the other factors that have contributed to breakthrough psychotic symptoms in patients treated with LAIs including poor adherence, substance use, concurrent mood disorders, poor treatment response, failed cross-titration, and insufficient dosing. Eligible subjects will undergo a screening visit to document that inclusion criteria are met and those meeting exclusion criteria are excluded. Participants will be assessed every 12 weeks to determine whether they remain in remission or meet criteria for a relapse. More comprehensive assessment will be completed at the beginning of the study (baseline visit), at the 24-week study midpoint and the 48-week study endpoint. Plasma antipsychotic levels will be measured at these three study time points to investigate associations between plasma levels and remission/relapse status as well as side effects. Plasma prolactin will also be measured to assess the association with sexual side effects. Hemoglobin A1c and measures of total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol will be obtained to assess the effects of SGA LAIs on these measures.

Clinical Trial Description

Rationale and Study Objectives In this study, we aim to determine the likelihood that relapse of psychosis will occur when patients with schizophrenia who have experienced a remission of their psychotic symptoms are adherent to treatment with a second generation antipsychotic (SGA) LAI on which they have been stable at a therapeutic dose for at least three months.

Primary objective:

1. To estimate the rate of psychotic relapse in patients with schizophrenia whose psychotic symptoms have remitted and who are adherent with second generation LAIs for maintenance treatment.

Secondary objectives:

1. To determine whether the risk of psychotic relapse is associated with antipsychotic plasma levels in patients treated with second generation LAIs.

Study design:

This prospective longitudinal cohort study will follow patients with schizophrenia who are treated with the second generation LAIs (paliperidone palmitate, risperidone or aripiprazole) for 48 weeks to determine the risk of psychotic symptom relapse when treatment adherence is established. The study is designed to minimize the other factors that have contributed to breakthrough psychotic symptoms in patients treated with LAIs including poor adherence, concurrent mood disorders, poor treatment response, failed cross-titration, and insufficient dosing.

Laboratory tests:

The following laboratory tests will be carried out at the baseline visit, 24-week visit and 48-week visit:

1. Urine drug screen - to document use of cannabis and other common recreational drugs. This will allow us to determine whether substance use is associated with the risk of relapse in remitted patients with established adherence to LAIs.

2. Plasma antipsychotic levels - to determine whether trough (pre-injection) plasma levels are associated with risk of relapse and medication side effects

3. Plasma prolactin - to determine whether the incidence and severity of sexual dysfunction is associated with antipsychotic plasma levels

The following laboratory tests will be carried out at the baseline visit and 48-week visit:

4. Hemoglobin A1c - to determine the effects of LAIs on blood sugar levels

5. Lipid panel - to determine the effects of LAIs on total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol

The target population is individuals diagnosed with schizophrenia whose psychotic symptoms have remitted and are receiving outpatient care at the Centre for Addiction and Mental Health (CAMH) in Toronto, Ontario, Canada. Patients who have been stabilized on long-acting injectable forms of either paliperidone palmitate, risperidone or aripiprazole with be invited to participate in this study.

Participants will be recruited from CAMH outpatient treatment teams in Toronto, Ontario, Canada, that provide follow-up to individuals diagnosed with schizophrenia including:

1. Downtown Central Flexible Assertive Community Treatment (DC-FACT)

2. Downtown West Flexible Assertive Community Treatment (DW-FACT)

3. Downtown East Flexible Assertive Community Treatment (DE-FACT)

4. Slaight Centre Early Intervention Service (SCEIS)

5. Forensic Outpatient Program for Schizophrenia (FOPS)

6. Psychosis Coordinated Care Service (PCCS)

7. General Psychosis Service (GPS)

All outpatients of the above clinics who are receiving treatment with LAI paliperidone, risperidone, or aripiprazole will be invited to participate in this study if they are considered to meet inclusion criteria and do not meet any of the exclusion criteria listed below. A screening visit will be scheduled for potential participants who express interest in the study. The study and procedures involved with be explained to eligible participants and informed consent will be obtained for study participation by the study research coordinator or research assistant. A baseline visit will then be scheduled.

Study Duration:

The study duration will be 48 weeks rather than 52 weeks as participants treated with LAIs are most commonly administered medication at intervals of two, three, four or twelve weeks. Each of these intervals would fit with major assessments as 24 weeks (study mid-point) and 48 weeks (study end-point).

Study Visit:

At the screening visit, the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) will be administered to determine if the subject meets criteria for schizophrenia and that they do not meet diagnoses that would exclude them from study participation. Screening for other exclusion criteria including medical disorders, concomitant medications, and suicide attempts or hospitalizations in the past 3 months, will be completed at this visit. Subjects who do not meet inclusion criteria or who meet exclusion criteria will be informed and will not participate in further assessments.

Following the Screening visit, all subjects will be assessed at the following time points:

Baseline, 12-week, 24-week, 36-week and 48-week visits, with more comprehensive assessments carried out at baseline, 24 weeks and 48 weeks. The following laboratory tests will be carried out at the baseline visit, 24-week visit and 48-week visit: urine drug screen, plasma antipsychotic levels, plasma prolactin. Height will be collected at baseline and weight and waist circumference will be collected at these time points. Hemoglobin A1c and a lipid panel will be obtained at baseline and 48 weeks. ;

Related Conditions & MeSH terms

• Recurrence
• Schizophrenia
• Schizophrenia Relapse

• NCT number: NCT05473741
• Study type: Observational
• Source: Centre for Addiction and Mental Health
• Contact: Robert B Zipursky, MD
• Phone: 416-535-8501
• Email: robert.zipursky@camh.ca
• Status: Recruiting
• Start date: January 9, 2023
• Completion date: December 31, 2025