Clozapine Versus Olanzapine as Treatment for Comorbid Psychotic Disorder and Substance Use Disorder

The purpose of this trial is to determine if patients with comorbid psychotic disorder and substance use disorder will continue in treatment longer if treated with clozapine than with olanzapine, and will have greater reductions in psychosis and in substance use if treated with clozapine than treated with olanzapine. The specific aims and hypotheses of this trial are: 1. To compare the enduring effectiveness and tolerability of clozapine and olanzapine, as measured by time to all-cause treatment discontinuation, over 12 weeks of follow-up; The investigators hypothesize that patients assigned to clozapine treatment will have significantly longer times to all cause treatment discontinuation, 2. To compare the total psychosis items scores between patients treated with clozapine and patients treated with olanzapine over 12 weeks of follow-up; The investigators hypothesize that patients treated with clozapine will have significantly lower total psychosis items scores than patients treated with olanzapine, and 3. To compare the frequencies of positive urine drug screens and blood alcohol levels (obtained weekly throughout 12 weeks of follow-up) between patients treated with clozapine and patients treated with olanzapine; The investigators hypothesize that patients treated with clozapine will have significantly fewer positive urine drug screens and blood alcohol levels than patients treated with olanzapine.

Study Overview

• Status: Unknown
• Conditions: Substance Use Disorders; Psychosis
• Intervention / Treatment: Drug: Clozapine; Drug: Olanzapine

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Evans, Georgia, United States, 30809
      • Sandarsh Surya

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-60 years of age, male or female (post-menopausal, surgically sterilized, or receiving either one of the listed contraception - depot contraceptive, Intrauterine device, or implanted hormonal contraceptive),
• who meet DSM-V criteria for schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, depression with psychotic features, or delusional disorder, and have ratings of Moderate or greater on at least one of the Brief Psychiatric Rating Scale psychosis items,
• who meet DSM-V criteria for at least one of alcohol, marijuana, cocaine, stimulant, or opioid use disorder, and have an admission urine drug screen positive for at least one of these substances,
• who have a stable living situation (family or supervised living, e.g. personal care home) to return to after release into the community,
• and who provide signed informed consent to participate (after testing for comprehension).

Exclusion Criteria:

• Prior failure to respond or tolerate clozapine or olanzapine
• Logistics that prevent outpatient follow-up at Serenity Behavioral Health Adult Outpatient services

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clozapine Arm	Drug: Clozapine; Subjects will be randomly assigned to clozapine or olanzapine and followed for up to 12 weeks with weekly visits.
Active Comparator: Olanzapine Arm	Drug: Olanzapine; Subjects will be randomly assigned to clozapine or olanzapine and followed for up to 12 weeks with weekly visits.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequencies of positive urine drug screens and breathalyzer alcohol levels	Participants will have weekly urine drug screens and alcohol level measurement using breathalyzer to monitor ongoing substance and alcohol abuse.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause treatment discontinuation	Discontinuation rate due to any cause (treatment non-compliance, worsening of mental health conditions, withdrawal of consent)	12 weeks
Brief Psychiatric Rating Scale (BPRS) - Positive Psychopathology items	BPRS scale is used to measure and monitor for symptoms of schizophrenia. For the purpose of the study, we will be measuring 4 items to monitor for positive psychopathology. The items are; Suspiciousness; Hallucinations; Unusual thought content; Conceptual disorganization Each item is rated on a scale of 1 to 7. 1 being condition not present and 7 being extreme form of the condition present. The maximum score a participant can score is 28 and minimum score is 4.	12 weeks

Collaborators and Investigators

• Sponsor: Augusta University

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2020
• Primary Completion (Anticipated): July 1, 2021
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: February 26, 2019
• First Submitted That Met QC Criteria: February 26, 2019
• First Posted (Actual): February 28, 2019

Study Record Updates

• Last Update Posted (Actual): March 23, 2020
• Last Update Submitted That Met QC Criteria: March 20, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Schizophrenia; Psychosis; Clozapine; Bipolar disorder; Schizoaffective disorder; Olanzapine; Major depressive disorder; Substance abuse
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Substance-Related Disorders; Disease; Psychotic Disorders; Mental Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Serotonin Antagonists; GABA Agents; GABA Antagonists; Olanzapine; Clozapine
• Other Study ID Numbers: 1303985

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No