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

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.

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Intellectual Disability; Psychosis
• Intervention / Treatment: Drug: Clozapine; Drug: haloperidol, pimozide, olanzapine, risperidone, amisulpride

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.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clara Rosso Fernández, PhD; Phone Number: +34 955 013414; Email: claram.rosso.sspa@juntadeandalucia.es

Study Locations

• Spain
  • Andújar, Spain
    • Unidad de Salud Mental Comunitaria Andújar
  • Armilla, Spain
    • Centro psicopedagógico Reina Sofía
  • Cabra, Spain
    • Unidad de Salud Mental Comunitaria Cabra
  • Castril, Spain
    • Residencia Rodríguez Penalva
  • Córdoba, Spain
    • Hospital Universitario Reina Sofia
  • Córdoba, Spain
    • Unidad de Salud Mental Comunitaria Córdoba Sur
  • Granada, Spain
    • Hospital Universitario Clinico San Cecilio
  • Granada, Spain
    • Fundación Purísima Concepción Hermanas Hospitalarias
  • Jerez De La Frontera, 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
  • Montilla, Spain
    • Unidad de Salud Mental Comunitaria Montilla
  • Montoro, Spain
    • Unidad de Salud Mental Comunitaria Montoro
  • Málaga, Spain
    • Hospital Regional Universitario
  • Málaga, Spain
    • Centro Asistencial San Juan de Dios
  • Reus, Spain
    • Villablanca Serveis Assistencials
  • Sanlúcar De Barrameda, Spain
    • Residencia de gravemente afectados Virgen de la Caridad
  • Seville, Spain, 41013
    • Hospital Universitario Virgen Del Rocio
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Ubrique, Spain
    • Centro Ocupacional El Curtido

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
Experimental: Clozapine; Pharmaceutical Form: Tablet Anatomical Therapeutic Chemical classification system (ATC Code): N: nervous system, N05: psycholeptic, N05A: antipsychotic, N05AH02: clozapine (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: Leponex; Nemex

What is the study measuring?

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
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
Quality of Life Improvement based on the 5 levels Quality of Life 5 dimensional (5D) 5 levels (5L) questionnaire (Euro-QoL 5D-5L scale)	Generic health status improvement measured by change from baseline to last study visit scores	Baseline and 12 Months

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Investigators: Principal Investigator: Benedicto Crespo Facorro, Professor, Andalusian Health Service

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2020
• Primary Completion (Estimated): January 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: August 25, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (Actual): August 27, 2020

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Schizophrenia Spectrum and Other Psychotic Disorders; Neurodevelopmental Disorders; Psychotic Disorders; Mental Disorders; Intellectual Disability; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; GABA Agents; Antidepressive Agents, Second-Generation; Anti-Dyskinesia Agents; GABA Antagonists; Selective Serotonin Reuptake Inhibitors; Olanzapine; Risperidone; Amisulpride; Haloperidol; Haloperidol decanoate; Clozapine; Pimozide
• Other Study ID Numbers: CLOZ-AID; 2020-000091-37 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No