CLOZAPINE Response in Biotype-1

NCT04580134 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: ( STU-2020-0989 )
• Study Type: interventional
• Target: 524
• Locations: 1 country
• Sites: 5

Brief Summary

The CLOZAPINE study is designed as a multisite study across 5 sites and is a clinical trial, involving human participants who are prospectively assigned to an intervention. The study will utilize a stringent randomized, double-blinded, parallel group clinical trial design. B2 group will serve as psychosis control with risperidone as medication control. The study is designed to evaluate effect of clozapine on the B1 participants, and the effect that will be evaluated is a biomedical outcome. The study sample will be comprised of individuals with psychosis, including 1) schizophrenia, 2) schizoaffective disorder and 3) psychotic bipolar I disorder. The investigators plan to initially screen and recruit n=524 (from both the existing B-SNIP library and newly-identified psychosis cases, \~50% each) in order to enroll n=320 (B1 and B2) into the RCT.

Conditions

Bipolar 1 Disorder; Schizophrenia; Schizoaffective Disorder

Keywords

Schizophrenia, Bipolar, Psychosis, Biomarker, Biotype, BSNIP, B-SNIP, IEA

Outcome Measures

Primary Outcomes (1)

• Change in the PANSS total score

  The change in the PANSS total score from the clinical trial baseline (W4) to the end of treatment (W18) will be a primary outcome measure. We predict that B1/clozapine will show a significantly larger change in the PANSS score from W4 to W18, compared to B1/risperidone, B2/clozapine and B2/risperidone. We will also examine the patterns of change in the PANSS score during the 'stable treatment' phase (W10-W18), across the same study groups. A mixed-effect repeated-measures ANCOVA \[2(Biotypes) × 2(clozapine/risperidone) × 2(time points\] will be used. We also predict that the reduction in the PANSS scores will correlate with increased IEA in B1/clozapine but not in B1/risperidone, B2/clozapine or B2/risperidone. Multivariate prediction models will be used.

  Week 4, Week 10 and Week 18

Study Arms (4)

Biotype 1 - Clozapine (B1C)

EXPERIMENTAL

Target doses will be up to clozapine 500mg po qd. In addition, several concomitant (open label) medications for symptomatic management will be available via the study protocol \[non-benzodiazepine sleep aid (melatonin, hydroxyzine); motor side effect treatments (benztropine, propranolol)\]. The doses for these medications will be consistent with those routinely used in a clinical practice: melatonin \[up to 10mg at bedtime\], hydroxyzine \[up to 100mg at bedtime\]; benztropine \[up to 4mg/day (2mg twice/day)\], propranolol \[up to 40mg/day (20mg twice/day)\].

Drug: clozapine

Biotype 1 - Risperidone (B1R)

PLACEBO COMPARATOR

Target doses will be up to risperidone 6mg po qd. In addition, several concomitant (open label) medications for symptomatic management will be available via the study protocol \[non-benzodiazepine sleep aid (melatonin, hydroxyzine); motor side effect treatments (benztropine, propranolol)\]. The doses for these medications will be consistent with those routinely used in a clinical practice: melatonin \[up to 10mg at bedtime\], hydroxyzine \[up to 100mg at bedtime\]; benztropine \[up to 4mg/day (2mg twice/day)\], propranolol \[up to 40mg/day (20mg twice/day)\].

Drug: risperidone

Biotype 2 - Clozapine (B2C)

ACTIVE COMPARATOR

Target doses will be up to clozapine 500mg po qd. In addition, several concomitant (open label) medications for symptomatic management will be available via the study protocol \[non-benzodiazepine sleep aid (melatonin, hydroxyzine); motor side effect treatments (benztropine, propranolol)\]. The doses for these medications will be consistent with those routinely used in a clinical practice: melatonin \[up to 10mg at bedtime\], hydroxyzine \[up to 100mg at bedtime\]; benztropine \[up to 4mg/day (2mg twice/day)\], propranolol \[up to 40mg/day (20mg twice/day)\].

Drug: clozapine

Biotype 2 - Risperidone (B2R)

PLACEBO COMPARATOR

Target doses will be up to risperidone 6mg po qd. In addition, several concomitant (open label) medications for symptomatic management will be available via the study protocol \[non-benzodiazepine sleep aid (melatonin, hydroxyzine); motor side effect treatments (benztropine, propranolol)\]. The doses for these medications will be consistent with those routinely used in a clinical practice: melatonin \[up to 10mg at bedtime\], hydroxyzine \[up to 100mg at bedtime\]; benztropine \[up to 4mg/day (2mg twice/day)\], propranolol \[up to 40mg/day (20mg twice/day

Drug: risperidone

Interventions

clozapine DRUG

Biotype 1 and Biotype 2

Also known as: Clozaril

Biotype 1 - Clozapine (B1C); Biotype 2 - Clozapine (B2C)

risperidone DRUG

Biotype 1 and Biotype 2

Also known as: Risperdal

Biotype 1 - Risperidone (B1R); Biotype 2 - Risperidone (B2R)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• y/o; males and females; all races and ethnicities; able to provide written informed consent; able to read, speak, and understand English; medically stable; meeting DSM-IV (SCID-based) criteria for schizophrenia, schizoaffective disorder, or bipolar I disorder with psychotic features (we will use DSM-IV to be consistent with prior B-SNIP samples); PANSS total score of ≥70 and at least one item scored ≥5 or two items scored ≥4 on PANSS Positive Subscale; normal baseline values for absolute neutrophil count (ANC above 1500/mm3)

You may not qualify if:

• premorbid intellectual ability estimate below 70 (WRAT-4, Word Reading subtest, age-corrected standardized score); comorbid DSM-IV diagnosis of alcohol or substance abuse in prior 1 month or substance dependence in prior 3 months; neurological (e.g., seizure disorder, stroke, traumatic brain injury with a loss of consciousness ≥ 30min) or severe medical condition (e.g., decompensated cardiovascular disorder, AIDS) that may affect central nervous system function; concomitant medications known to affect EEG properties (i.e., lithium, anticonvulsants, benzodiazepines) or strong CYP 1A2 inhibitors (e.g., ciprofloxacin, enoxacin) or strong CYP 3A4 inducers (e.g., phenytoin, carbamazepine, phenobarbital, rifampin) which cannot be safely discontinued; vulnerable populations (e.g., pregnant, nursing, incarcerated); unwilling to use reliable means of contraception; history of neuroleptic malignant syndrome; prior treatment with clozapine, prior treatment with long-acting injectable antipsychotics that are 1-month formulations within the past 3 months and for 3-month formulations within the past 6 months; intolerable side effects to either clozapine or risperidone in lifetime, or a previously failed trial of either clozapine or risperidone at adequate doses in lifetime; history of drug reaction with eosinophilia and systemic symptoms syndrome (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS); high risk for suicide defined as more than 1 attempt in past 12 months that required medical attention, any attempt in the past 3 months or current suicidal ideation with plan and intent such that outpatient care is precluded; current homicidal ideation with plan and intent such that outpatient care is precluded.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Beth Israel Deaconess Medical Center: collaborator
• Hartford Hospital: collaborator
• University of Georgia: collaborator
• University of Chicago: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (5)

Hartford Healthcare

Hartford, Connecticut, 06106, United States

RECRUITING

University of Georgia

Athens, Georgia, 30602, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60615, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

RECRUITING

UT Southwestern Medical Center

Dallas, Texas, 75235, United States

RECRUITING

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Clozapine; Risperidone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Carol Tamminga, M.D.

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Asha Philip

CONTACT

214-648-5276; asha.philip@utsouthwestern.edu

Emily McNeil

CONTACT

214-648-1683; emily.mcneil@utsouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All participants and those who interact with them are blinded to study medication. The pharmacy dispensing team and the Safety Officer will remain unblinded for safety reasons.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair, Department of Psychiatry

Model Details: Individuals who previously participated in a B-SNIP trial who have already been biotyped will be grouped accordingly. New incoming individuals will have their Biotype completed. Those with Biotypes 1 and 2 will be recruited into this protocol. Anyone with Biotype 3 will be excluded from this protocol, but their information will be retained for use in a later study. Biotypes 1 and 2 will be separated into two groups. Each Biotype, B1 and B2, will be randomized between risperidone and clozapine to create parallel comparator groups.

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 8, 2020
• Study Start: March 1, 2022
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: February 6, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)