Clinical trial NCT04529226: Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Psychosis
Intellectual Disability
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
First posted: 2020-08-27
Enrollment: 75
Sex: ALL
Minimum age (years): 16
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Clinical improvement based on Clinical Global Impression-Schizophrenia (CGI-SCH) scale score.
timeFrame: Baseline and 12 Months
Secondary outcomes:
measure: Clinical improvement based on Positive and Negative Syndrome Scale (PANSS)
timeFrame: Baseline and 12 Months
measure: Clinical improvement based on Scale for the Assessment of Negative Symptoms (SANS)
timeFrame: Baseline and 12 Months
measure: Quality of Life Improvement based on the 5 levels Quality of Life 5 dimensional (5D) 5 levels (5L) questionnaire (Euro-QoL 5D-5L scale)
timeFrame: Baseline and 12 Months
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Up to 28 days after the last investigational medicinal product administration
Other outcomes:
Locations:
city: Andújar
country: Spain
facility: Unidad de Salud Mental Comunitaria Andújar
city: Armilla
country: Spain
facility: Centro psicopedagógico Reina Sofía
city: Cabra
country: Spain
facility: Unidad de Salud Mental Comunitaria Cabra
city: Castril
country: Spain
facility: Residencia Rodríguez Penalva
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Córdoba
country: Spain
facility: Unidad de Salud Mental Comunitaria Córdoba Sur
city: Granada
country: Spain
facility: Fundación Purísima Concepción Hermanas Hospitalarias
city: Granada
country: Spain
facility: Hospital Universitario Clínico San Cecilio
city: Jerez De La Frontera
country: Spain
facility: Hospital Universitario de Jerez
city: Jerez De La Frontera
country: Spain
facility: Residencia de Adultos María Dacia González Gordón
city: Jerez De La Frontera
country: Spain
facility: Residencia para personas con Discapacidad intelectual Gravemente Afectadas Vista Hermosa
city: Montilla
country: Spain
facility: Unidad de Salud Mental Comunitaria Montilla
city: Montoro
country: Spain
facility: Unidad de Salud Mental Comunitaria Montoro
city: Málaga
country: Spain
facility: Centro Asistencial San Juan de Dios
city: Málaga
country: Spain
facility: Hospital Regional Universitario
city: Reus
country: Spain
facility: Villablanca Serveis Assistencials
city: Sanlúcar De Barrameda
country: Spain
facility: Residencia de gravemente afectados Virgen de la Caridad
city: Seville
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Seville
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Ubrique
country: Spain
facility: Centro Ocupacional El Curtido
Study officials:
affiliation: Andalusian Health Service
name: Benedicto Crespo Facorro, Professor
role: PRINCIPAL_INVESTIGATOR
References: