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

Sponsor

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla (Other)

Overall Status

Recruiting

CT.gov ID

NCT04529226

Collaborator

(none)

114

Enrollment

Locations

Arms

38.2

Anticipated Duration (Months)

5.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Psychosis Intellectual Disability	Drug: Clozapine Drug: haloperidol, pimozide, olanzapine, risperidone, amisulpride	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

114 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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.

Actual Study Start Date :

Nov 26, 2020

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clozapine Pharmaceutical Form: Tablet ATC Code: N05AH02	Drug: 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 Other Names: Nemea Leponex
Active Comparator: Control Usual antipsychotic medication used in the treatment of treatment-resistant psychosis.	Drug: haloperidol, pimozide, olanzapine, risperidone, amisulpride Treatment as usual using first-generation or second-generation antipsychotics

Arm

Intervention/Treatment

Experimental: Clozapine

Pharmaceutical Form: Tablet ATC Code: N05AH02

Drug: 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

Other Names:

Nemea

Leponex

Active Comparator: Control

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

Drug: haloperidol, pimozide, olanzapine, risperidone, amisulpride

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

Outcome Measures

Primary Outcome Measures

Clinical improvement based on Clinical Global Impression-Schizophrenia (CGI-SCH) scale score. [Baseline and 12 Months]
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

Secondary Outcome Measures

Clinical improvement based on Positive and Negative Syndrome Scale (PANSS) [Baseline and 12 Months]
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
Clinical improvement based on Scale for the Assessment of Negative Symptoms (SANS) [Baseline and 12 Months]
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
Quality of Life Improvement based on the 5-level Quality of Life 5-dimensional questionnaire (Euro-QoL 5D-5L scale) [Baseline and 12 Months]
Generic health status improvement measured by change from baseline to last study visit scores
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]
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Unidad de Salud Mental Comunitaria Andújar	Andújar	Spain
2	Centro psicopedagógico Reina Sofía	Armilla	Spain
3	Unidad de Salud Mental Comunitaria Cabra	Cabra	Spain
4	Residencia Rodríguez Penalva	Castril	Spain
5	Hospital Universitario Reina Sofía	Córdoba	Spain
6	Unidad de Salud Mental Comunitaria Córdoba Sur	Córdoba	Spain
7	Fundación Purísima Concepción Hermanas Hospitalarias	Granada	Spain
8	Hospital Universitario Clínico San Cecilio	Granada	Spain
9	Hospital Universitario de Jerez	Jerez De La Frontera	Spain
10	Residencia de Adultos María Dacia González Gordón	Jerez De La Frontera	Spain
11	Residencia para personas con Discapacidad intelectual Gravemente Afectadas Vista Hermosa	Jerez De La Frontera	Spain
12	Unidad de Salud Mental Comunitaria Montilla	Montilla	Spain
13	Unidad de Salud Mental Comunitaria Montoro	Montoro	Spain
14	Centro Asistencial San Juan de Dios	Málaga	Spain
15	Hospital Regional Universitario	Málaga	Spain
16	Villablanca Serveis Assistencials	Reus	Spain
17	Residencia de gravemente afectados Virgen de la Caridad	Sanlúcar De Barrameda	Spain
18	Hospital Universitario Virgen Macarena	Seville	Spain	41009
19	Hospital Universitario Virgen del Rocío	Seville	Spain	41013
20	Centro Ocupacional El Curtido	Ubrique	Spain