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

NCT ID: NCT04529226

Last Updated: 2024-03-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-26
• Study Completion Date: 2025-12-30

Brief Summary

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.

Detailed Description

Randomized, open-label, multicenter phase II clinical trial that seeks to evaluate the safety and efficacy of clozapine versus standard clinical treatment in patients between the ages of 16 and 55 with intellectual disability and treatment-resistant psychosis.

Clozapine is the most effective antipsychotic for patients with non-affective psychosis who do not respond to other first and second generation antipsychotic treatments. In addition, it has been shown to be very effective in another series of clinical situations such as hostility and aggressiveness, polydipsia and in behavioral disorders and psychosis, frequent situations in people with intellectual disabilities.

The primary objective is to assess the efficacy and safety of clozapine versus standard clinical practice treatment in patients with intellectual disability and resistant psychotic disorder, as measured by change in Clinical Global Impression: Clinical Global Impression-Schizophrenia scale (ICG-SCH) global score over trial visits.

The study determines to reach a sample size of 114 patients distributed among the 25 active centers. Randomization is 1:1 and consists of 6 visits to the center spread over 12 months. At each visit, the patient will undergo a physical examination and sample collection, along with a clinical and cognitive evaluation using the scales provided in accordance with the clinical guidelines.

In addition, if the patient falls into the experimental arm (Clozapine), it is necessary to collect a blood sample weekly during the first 18 weeks and biweekly until completing the 12 months of the study, so that the medical team has special control in the analytical parameters.

Conditions

Psychosis; Intellectual Disability

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Clozapine

Pharmaceutical Form: Tablet Anatomical Therapeutic Chemical classification system (ATC Code): N: nervous system, N05: psycholeptic, N05A: antipsychotic, N05AH02: clozapine (N05AH02)

Group Type: EXPERIMENTAL

Clozapine

Intervention Type: DRUG

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

Control

Usual antipsychotic medication used in the treatment of treatment-resistant psychosis.

Group Type: ACTIVE_COMPARATOR

haloperidol, pimozide, olanzapine, risperidone, amisulpride

Intervention Type: DRUG

Treatment as usual using first-generation or second-generation antipsychotics

Interventions

Clozapine

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

Intervention Type: DRUG

haloperidol, pimozide, olanzapine, risperidone, amisulpride

Treatment as usual using first-generation or second-generation antipsychotics

Intervention Type: DRUG

Other Intervention Names

Nemex; Leponex

Eligibility Criteria

Inclusion Criteria

• Subjects aged between 16 and 55 years
• Diagnosis of intellectual disability according to the Diagnostic and Statistical Manual of Mental Disorders Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (confirmed by a Intelligence Quotient (IQ) Score between 35 and 70 in the Kaufman test)
• Diagnosis of psychosis according to the Diagnostic and Statistical Manual of Mental Disorders (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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Benedicto Crespo Facorro, Professor

Role: PRINCIPAL_INVESTIGATOR

Andalusian Health Service

Locations

Unidad de Salud Mental Comunitaria Andújar

Andújar, , Spain

Centro psicopedagógico Reina Sofía

Armilla, , Spain

Unidad de Salud Mental Comunitaria Cabra

Cabra, , Spain

Residencia Rodríguez Penalva

Castril, , Spain

Hospital Universitario Reina Sofía

Córdoba, , Spain

Unidad de Salud Mental Comunitaria Córdoba Sur

Córdoba, , Spain

Fundación Purísima Concepción Hermanas Hospitalarias

Granada, , Spain

Hospital Universitario Clínico San Cecilio

Granada, , Spain

Hospital Universitario de Jerez

Jerez de la Frontera, , Spain

Residencia de Adultos María Dacia González Gordón

Jerez de la Frontera, , Spain

Residencia para personas con Discapacidad intelectual Gravemente Afectadas Vista Hermosa

Jerez de la Frontera, , Spain

Centro Asistencial San Juan de Dios

Málaga, , Spain

Hospital Regional Universitario

Málaga, , Spain

Unidad de Salud Mental Comunitaria Montilla

Montilla, , Spain

Unidad de Salud Mental Comunitaria Montoro

Montoro, , Spain

Villablanca Serveis Assistencials

Reus, , Spain

Residencia de gravemente afectados Virgen de la Caridad

Sanlúcar de Barrameda, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Centro Ocupacional El Curtido

Ubrique, , Spain

Countries

Spain

References

Alemany-Navarro M, Sanchez-Barbero B, Reguera-Pozuelo P, Altea-Manzano L, Gomez-Garrido A, Rocha-Gonzalez I, Garrido-Torres N, Ruiz-Veguilla M, Garcia-Cerro S, Rosso-Fernandez CM, Villagran-Moreno JM, Sarramea F, Cervilla-Ballesteros J, Martinez-Leal R, Mayoral-Cleries F; CLOZ-AID Group; Crespo-Facorro B. Efficacy of clozapine versus standard treatment in adult individuals with intellectual disability and treatment-resistant psychosis (CLOZAID): study protocol of a multicenter randomized clinical trial. Front Psychiatry. 2024 May 14;15:1400621. doi: 10.3389/fpsyt.2024.1400621. eCollection 2024.

Reference Type: DERIVED

PMID: 38807685 (View on PubMed)

Other Identifiers

2020-000091-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLOZ-AID

Identifier Type: -

Identifier Source: org_study_id