Lumateperone Study

Study Overview
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Brief Summary
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The main question this study is trying to answer is whether lumateperone, an FDA-approved antipsychotic drug, can help reduce possible side effects of clozapine, such as weight gain and elevated levels of sugar and bad cholesterol. Participants will be randomly assigned to either take lumateperone (Caplyta) or a placebo for 12 weeks, in addition to their regularly prescribed clozapine. During their participation, patients will answer questions about their psychiatric and daily functioning, have blood drawn, and have their body composition analyzed (similar to stepping on a scale).

Detailed Description
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This is a 12-week study in which we investigate how adjunctive lumateperone affects lipid particle size and body composition in clozapine-treated patients with schizophrenia; in addition, we will investigate if lumateperone improves insomnia. Outcome measures will record a variety of assessments related to participants' psychiatric symptoms, psychosocial functioning, and biological outcomes.

Official Title
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Metabolic Effects of Adjunctive Lumateperone Treatment in Clozapine-Treated Patients With Schizophrenia

Conditions
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Schizophrenia, Schizo Affective Disorder

Intervention / Treatment
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* Drug: Lumateperone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets the DSM-5 criteria for diagnoses of schizophrenia or schizoaffective disorder based on the MINI International Neuropsychiatric Interview (MINI 7.0) On clozapine treatment for at least 6 months Stable dose of antipsychotic treatment for at least 1 month Well established compliance with outpatient medications Subjects of child-bearing potential are required to practice appropriate birth control methods during the study. Exclusion Criteria: Psychiatrically unstable per clinical judgement by the principal investigator Patients not on stable dose of antipsychotic medications Currently meets DSM-5 criteria for any substance use disorder other than caffeine and nicotine Significant, unstable medical conditions including severe cardiovascular, hepatic, renal or other medical diseases History of a seizure disorder Pregnancy or breastfeeding On lumateperone treatment in the past 3 months On a dopamine partial agonist antipsychotic agent in the past 3 months (aripiprazole, brexpiprazole, cariprazine)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, double-blind, placebo-controlled trial.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Subject will take placebo for 12 weeks, in addition to their regular medications.<br>|
| Experimental: Lumateperone<br> | Drug: Lumateperone<br>* Subject will take lumateperone (Caplyta) for 12 weeks, in addition to their regular medications.<br>* Other names: Caplyta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Mass Index (BMI) | Participant Body Mass Index will be measured by standard methods | Week 0, Week 6, and Week 12 | 
| Waist Circumference | Participant Waist Circumference will be measured by standard methods | Week 0, Week 6, and Week 12 | 
| Body Composition - Fat Mass | Body Composition will be assessed using the research-grade medical body composition analyzer Seca 515/514. Fat mass will be measured in grams. | Week 0 and Week 12 | 
| Body Composition - Total Body Mass | Body Composition will be assessed using the research-grade medical body composition analyzer Seca 515/514. Total Body Mass will be measured in grams. | Week 0 and Week 12 | 
| Body Composition - Fat Percentage | Body Composition will be assessed using the research-grade medical body composition analyzer Seca 515/514. Fat Percentage will be calculated as fat mass (in grams) divided by total mass (in grams). | Week 0 and Week 12 | 
| HBA1C | Participant HBA1C will be measured using standard labs | Week 0 and Week 12 | 
| Fasting Insulin | Participant Fasting Insulin will be measured using standard labs | Week 0, Week 6, and Week 12 | 
| LDL Particle | LDL particle size will be determined using the NMR spectroscopy (LipoScience, Raleigh, NC) | Week 0 and Week 12 | 
| Small LDL Particle | Small LDL particle size will be determined using the NMR spectroscopy (LipoScience, Raleigh, NC) | Week 0 and Week 12 | 
| Large HDL Particle | Large HDL Particle size will be determined using the NMR spectroscopy (LipoScience, Raleigh, NC) | Week 0 and Week 12 | 
| Large VLDL Particle | Large VLDL Particle size will be determined using the NMR spectroscopy (LipoScience, Raleigh, NC) | Week 0 and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Symptoms Scale (PANSS) | PANSS is a measure used to assess symptom severity in patients with schizophrenia. It consists of three sections: Positive scale has 7 items, Negative scale has 7 items, and General Psychopathology has 16 items. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. | Week 0, Week 6, and Week 12 | 
| Calgary Depression Scale (CDRS) | The CDRS is used to assess depression symptoms in patients with schizophrenia. | Week 0, Week 6, and Week 12 | 
| Clinical Global Impression - Severity Scale (CGI-S) | The CGI-S is an observer rated scale. The CGI-S measures illness severity on a 7-point Likert scale 1) Normal, not at all ill, 2) Borderline mentally ill, 3) Mildly ill, 4) Moderately ill, 5) Markedly ill, 6) Severely ill, and 7) Among the most extremely ill patient. | Week 0, Week 6, and Week 12 | 
| Clinical Global Impression - Improvement Scale (CGI-I) | The CGI-I is an observer rated scale. The CGI-I is used to measure improvement in illness and uses a 7-point Likert scale: 1) Very much improved, 2) Much improved, 3) Minimally improved, 4) No change 5) Minimally worse, 6) Much worse, 7) Very much worse. | Week 0, Week 6, and Week 12 | 
| Insomnia Severity Index (ISI) | The ISI is a 7-question survey assessing symptoms of insomnia. The maximum score is 28 with higher scores indicating greater severity. The ISI is a reliable and valid instrument to assess insomnia and treatment response. | Week 0, Week 6, and Week 12 | 
| Henrichs Carpenter Quality of Life Scale (QLS) | The QLS is a 21-item scale providing information on symptoms and functioning in patients with schizophrenia. | Week 0, Week 6, and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clozapine