Recruiting

ClozapineCLOZAPINE Response in Biotype-1

Sponsor:

University of Texas Southwestern Medical Center

Code:

NCT04580134

Conditions

Schizophrenia

Schizoaffective Disorder

Bipolar 1 Disorder

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Not accepted

Interventions

clozapine

risperidone

Study Details

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

Schizophrenia

Schizoaffective Disorder

Bipolar 1 Disorder

Study ID

NCT04580134

Start date

Mar 1, 2022

Status verified date

May, 2026

Completion date

Apr 30, 2027

Anticipated

Primary completion date

Apr 30, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Not accepted

Inclusion Criteria:

18-60y/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)

Exclusion Criteria:

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.

Study Design

Enrollment

524 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Biotype 1 - Clozapine (B1C)

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 \[up to 40mg/day (20mg twice/day)\].

placebo comparator: Biotype 1 - Risperidone (B1R)

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 \[up to 40mg/day (20mg twice/day)\].

active comparator: Biotype 2 - Clozapine (B2C)

placebo comparator: Biotype 2 - Risperidone (B2R)

Interventions

clozapine

Biotype 1 and Biotype 2

risperidone

Biotype 1 and Biotype 2

Primary outcome measure

Change in the PANSS total score [ Time Frame: Week 4, Week 10 and Week 18 ]

Central Contacts and Locations

Central contacts

Asha Philip

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

Emily McNeil

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

Locations

Hartford Healthcare

Recruiting

Hartford, Connecticut, United States, 06106

Contacts

Dr. Godfrey Pearlson

860-545-7757 Godfrey.Pearlson@hhchealth.org

Aarti Kotecha

860-545-7767 Aarti.Kotecha@hhchealth.org

University of Georgia

Recruiting

Athens, Georgia, United States, 30602

Contacts

Isaac Doss

706-255-7445 Isaac.Doss@uga.edu

University of Chicago

Recruiting

Chicago, Illinois, United States, 60615

Contacts

Sanjana Venkat

773-230-6624 sanjanav1@uchicago.edu

Aashana Daru

773-230-6624 adaru@bsd.uchicago.edu

Beth Israel Deaconess Medical Center

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Gautami Shashidhar

617-754-1244 gshashid@bidmc.harvard.edu

Diane Beckman

339-364-8464 dkbeckma@bidmc.harvard.edu

UT Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75235

Contacts

Asha Philip

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

Yelonda Williams, B.A

214/645-2784 yelonda.williams@utsouthwestern.edu

More Information

Sponsor

University of Texas Southwestern Medical Center

Last update posted

May 11, 2026

Last verified

May, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-26. This information was provided to ClinicalTrials.gov by University of Texas Southwestern Medical Center on 2026-05-11. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.