Antipsychotic Response to Clozapine in B-SNIP Biotype-1 (Clozapine)
Schizophrenia, Schizoaffective Disorder, Bipolar 1 Disorder
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, Bipolar, Psychosis, Biomarker, Biotype, BSNIP, B-SNIP, IEA
Eligibility Criteria
Inclusion Criteria:
- 18-50y/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.
Sites / Locations
- UT Southwestern Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Placebo Comparator
Active Comparator
Placebo Comparator
Biotype 1 - Clozapine (B1C)
Biotype 1 - Risperidone (B1R)
Biotype 2 - Clozapine (B2C)
Biotype 2 - Risperidone (B2R)
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)].
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)].
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)].
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