Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis

Study Overview
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Brief Summary
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This clinical trial will prove whether a large number of people with intellectual disability and treatment-resistant psychosis could benefit from the use of clozapine. Benefit will mean a measurable significant improvement in subjects' clinical response and quality of life.

Official Title
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A Randomized, Multicenter Clinical Trial to Assess the Efficacy and Safety of Clozapine vs Treatment as Usual for Treatment-resistant Psychosis in Adolescents and Young Adults With Intellectual Disability.

Conditions
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Psychosis, Intellectual Disability

Intervention / Treatment
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* Drug: Clozapine
* Drug: haloperidol, pimozide, olanzapine, risperidone, amisulpride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged between 16 and 40 years Diagnosis of intellectual disability according to the Diagnostic and Statistical Manual of Mental Disorders DSM-5 (confirmed by a IQ Score between 35 and 70 in the Kaufman test) Diagnosis of psychosis according to the DSM-5 (confirmed by clinical interview). Treatment Resistant to antipsychotic drugs except clozapine. Behavioural disturbances and self-injurious behaviour over the last 6 months. Written informed consent of patients or legal representative. Negative pregnancy test (if apply) Exclusion Criteria: Leukocytes < 3500/mm3 and neutrophils < 2000/mm3. Hypersensitivity to clozapine or excipients. Myeloproliferative disorders Uncontrolled epilepsy in the last 2 years. Paralytic ileus in the last 3 months. Diagnosis of an autism spectrum disorder Pregnancy and breastfeeding Any diseases with clozapine contraindicated. Any uncontrolled serious condition Need of treatment with more than one antipsychotic drug or electroconvulsive therapy Treatment with quinolones, drugs that cause agranulocytosis or drugs that affect the cytochrome P-450 enzymes. Risk of suicide based on the Columbia-Suicide Severity Rating Scale

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clozapine<br>Pharmaceutical Form: Tablet ATC Code: N05AH02 | Drug: Clozapine<br>* Start treatment with 12.5 mg every 12 hours with the recommendation to increase dosage by 25-50 mg/day provided it is well tolerated up to a level of 300-450 mg/day at the end of the second week<br>* Other names: Leponex;|
| Active Comparator: Control<br>Usual antipsychotic medication used in the treatment of treatment-resistant psychosis. | Drug: haloperidol, pimozide, olanzapine, risperidone, amisulpride<br>* Treatment as usual using first-generation or second-generation antipsychotics<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical improvement based on Clinical Global Impression-Schizophrenia (CGI-SCH) scale score. | Overall Severity of Illness as measured by change from baseline to last study visit score Minimum value = 1 Normal, not ill Maximum value = 7 Among the most severely ill | Baseline and 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical improvement based on Positive and Negative Syndrome Scale (PANSS) | Clinical improvement as measured by change from baseline to last study visit score Subjects rated from 1 to 7 on 30 different symptoms (items). Positive scale 7 Items. minimum score = 7, maximum score = 49 Negative scale 7 Items. minimum score = 7, maximum score = 49 General Psychopathology scale 16 Items. minimum score = 16, maximum score = 112 PANSS Total score minimum = 30, maximum = 210 | Baseline and 12 Months | 
| Clinical improvement based on Scale for the Assessment of Negative Symptoms (SANS) | Clinical improvement as measured by change from baseline to last study visit score. SANS is split into 5 domains, and within each domain separate symptoms are rated through a 6-point scale from 0 (absent) to 5 (severe). SANS Total score minimum = 0, maximum = 125 | Baseline and 12 Months | 
| Quality of Life Improvement based on the 5-level Quality of Life 5-dimensional questionnaire (Euro-QoL 5D-5L scale) | Generic health status improvement measured by change from baseline to last study visit scores | Baseline and 12 Months | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Up to 28 days after the last investigational medicinal product administration |