PsychosisPhase 2CLOZ-AIDNCT04529226
Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
A Phase 2 study testing Clozapine and haloperidol, pimozide, olanzapine, risperidone, amisulpride in people with Psychosis and Intellectual Disability, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 20 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 55 years
- Conditions the study is for
- Psychosis, Intellectual Disability
- What is being tested?
- Clozapine and haloperidol, pimozide, olanzapine, risperidone, amisulpride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 20 sitesSpain
- Study dates
- 26 Nov 2020to 30 Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
Spain20 sites
Unidad de Salud Mental Comunitaria Andújar
Andújar
Centro psicopedagógico Reina Sofía
Armilla
Unidad de Salud Mental Comunitaria Cabra
Cabra
Residencia Rodríguez Penalva
Castril
Hospital Universitario Reina Sofía
Córdoba
Unidad de Salud Mental Comunitaria Córdoba Sur
Córdoba
Fundación Purísima Concepción Hermanas Hospitalarias
Granada
Hospital Universitario Clínico San Cecilio
Granada
Hospital Universitario de Jerez
Jerez de la Frontera
Residencia de Adultos María Dacia González Gordón
Jerez de la Frontera
Residencia para personas con Discapacidad intelectual Gravemente Afectadas Vista Hermosa
Jerez de la Frontera
Centro Asistencial San Juan de Dios
Málaga
Hospital Regional Universitario
Málaga
Unidad de Salud Mental Comunitaria Montilla
Montilla
Unidad de Salud Mental Comunitaria Montoro
Montoro
Villablanca Serveis Assistencials
Reus
Residencia de gravemente afectados Virgen de la Caridad
Sanlúcar de Barrameda
Hospital Universitario Virgen Macarena
Seville, 41009
Hospital Universitario Virgen del Rocío
Seville, 41013
Centro Ocupacional El Curtido
Ubrique
About this study
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.
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.
Read the 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
- Being tested
- Clozapine, haloperidol, pimozide, olanzapine, risperidone, amisulpride
- Medical subject headings
- Psychotic Disorders, Intellectual Disability
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClozapineDrug
Also called Nemex, Leponex
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
haloperidol, pimozide, olanzapine, risperidone, amisulprideDrug
Treatment as usual using first-generation or second-generation antipsychotics
| Study group | Role | What they receive |
|---|---|---|
| Clozapine | Experimental | Pharmaceutical Form: Tablet Anatomical Therapeutic Chemical classification system (ATC Code): N: nervous system, N05: psycholeptic, N05A: antipsychotic, N05AH02: clozapine (N05AH02) Receives: Drug: Clozapine |
| Control | Active comparator | Usual antipsychotic medication used in the treatment of treatment-resistant psychosis. Receives: Drug: haloperidol, pimozide, olanzapine, risperidone, amisulpride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline and 12 Months
Secondary outcomes (4)
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
Measured: 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
Measured: Baseline and 12 Months
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
Measured: 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
Measured: Up to 28 days after the last investigational medicinal product administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2020
- Study start26 Nov 2020
- Primary completion30 Jan 2025 (estimated)
- Study completion30 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PsychosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benedicto Crespo Facorro, Professor, Principal investigator, Andalusian Health Service
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04529226
- Sponsor's protocol ID
- CLOZ-AID
- Other IDs
- 2020-000091-37
- Acronym
- CLOZ-AID
- Status last verified
- Mar 2024
- First submitted
- 25 Aug 2020
- Last updated
- 20 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 38807685
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04529226
- Acronym / sponsor ID
- CLOZ-AID / CLOZ-AID
- Conditions
- Psychosis, Intellectual Disability
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en SevillaUniversity, hospital or other
- Study start
- 26 Nov 2020 (actual)
- Primary completion
- 30 Jan 2025 (estimated)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 27 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clozapine | Experimental | Drug: ClozapinePharmaceutical Form: Tablet Anatomical Therapeutic Chemical classification system (ATC Code): N: nervous system, N05: psycholeptic, N05A: antipsychotic, N05AH02: clozapine (N05AH02) |
| Control | Active comparator | Drug: haloperidol, pimozide, olanzapine, risperidone, amisulprideUsual antipsychotic medication used in the treatment of treatment-resistant psychosis. |
Who may qualify
- Ages
- 16 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClozapineAlso: Nemex, LeponexStart 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 | Drug | Clozapine |
| haloperidol, pimozide, olanzapine, risperidone, amisulprideTreatment as usual using first-generation or second-generation antipsychotics | Drug | Control |
Primary outcome
Clinical improvement based on Clinical Global Impression-Schizophrenia (CGI-SCH) scale score.
Time frame: 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
4 secondary outcomes
Clinical improvement based on Positive and Negative Syndrome Scale (PANSS)
Time frame: Baseline and 12 Months
Clinical improvement based on Scale for the Assessment of Negative Symptoms (SANS)
Time frame: Baseline and 12 Months
Quality of Life Improvement based on the 5 levels Quality of Life 5 dimensional (5D) 5 levels (5L) questionnaire (Euro-QoL 5D-5L scale)
Time frame: Baseline and 12 Months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: Up to 28 days after the last investigational medicinal product administration
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2024.
- Derived from this study: PubMed 38807685Alemany-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benedicto Crespo Facorro, Professor principal investigator
Andalusian Health Service
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Clozapine and haloperidol, pimozide, olanzapine, risperidone, amisulpride in people with Psychosis and Intellectual Disability, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 20 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical improvement based on Clinical Global Impression-Schizophrenia (CGI-SCH) scale score. (time frame: Baseline and 12 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04529226, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2024.