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

Phase 4

Recruiting

• Conditions: Schizophrenia; Schizo Affective Disorder
• Interventions: Drug: Placebo; Drug: Lumateperone

• Registration Number: NCT06174116
• Lead Sponsor: University of Massachusetts, Worcester

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2023-12-08
• Study First Submitted QC: 2023-12-08
• Study First Posted: 2023-12-18
• Study Start: 2024-04-02
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-15
• Last Update Posted: 2025-05-20
• Primary Completion: 2026-08
• Study Completion: 2026-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	2 Placebo capsules taken orally per day for 12 weeks
Lumateperone	Lumateperone	42mg (two 21mg capsules) lumateperone (Caplyta) taken orally per day for 12 weeks

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Positive and Negative Symptoms Scale (PANSS)	Week 0, Week 6, and Week 12	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.
Calgary Depression Scale (CDRS)	Week 0, Week 6, and Week 12	The CDRS is used to assess depression symptoms in patients with schizophrenia.
Clinical Global Impression - Severity Scale (CGI-S)	Week 0, Week 6, and Week 12	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.
Clinical Global Impression - Improvement Scale (CGI-I)	Week 0, Week 6, and Week 12	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.
Insomnia Severity Index (ISI)	Week 0, Week 6, and Week 12	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.
Henrichs Carpenter Quality of Life Scale (QLS)	Week 0, Week 6, and Week 12	The QLS is a 21-item scale providing information on symptoms and functioning in patients with schizophrenia.

Trial Locations

Locations (1)

UMass Chan Medical School; 🇺🇸 Worcester, Massachusetts, United States