Clozapine Versus Other Atypical Antipsychotics for Bipolar Disorder

NCT02562287 | Unknown Phase 4

• 1 other identifier: 32356214200005327
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The clinical use of clozapine has been an unequivocal advance in the treatment of schizophrenia, a chronic and severe mental illness. A wealth of clinical data demonstrates it offers enhanced efficacy on both positive and negative symptomatology, improving cognition, functioning and quality of life. It is also associated with improved compliance and a continued efficacy in long-term treatment that can be translated into a reduction of suicidality and all-cause mortality. Because of preclinical evidence that it modulates neuroplasticity and prefrontal cortex connectivity, clozapine may be an interesting strategy for further severe psychotic illnesses. Nevertheless, even considering the growing use of other atypical antipsychotics in the management of bipolar disorder, a role for clozapine has been poorly defined. The clinical evidence-base for its use in this condition is largely based on uncontrolled naturalistic trials and retrospective studies and chart reviews. Several of these have supported clozapine's efficacy in treatment-resistant bipolar disorder. Possibly because of clozapine's profile of adverse effects and lack of interest from pharmaceutical companies, only two randomized trials have examined its effectiveness. Both suggest clinically relevant antimanic and mood-stabilizing properties. Therefore, the primary objective of this trial is to determine the effectiveness of clozapine for treatment-resistant bipolar disorder. Secondary objectives include examining the effects of treatment with clozapine on cognition and functioning of patients with bipolar disorder. Tolerability and safety of long-term clozapine use will also be examined. To that end, the investigators will conduct a clinical trial with 54 patients with a history of treatment resistance. Patients will be randomized to either open-label treatment with clozapine, in combination with lithium or valproate, or open-label treatment with an atypical antipsychotic with consistent evidence of efficacy in the treatment of bipolar disorder (olanzapine, quetiapine or risperidone), also in combination with lithium or valproate. Patients will be followed for one-year and time to all-cause treatment failure will be the primary outcome measure. It is the belief of the investigators that this study will generate meaningful clinical data of tremendous importance to validate clozapine as a legitimate treatment option for treatment-resistant bipolar disorder.

Conditions

Bipolar Disorder

Outcome Measures

Primary Outcomes (1)

• Functioning according to Functioning Assessment Short-Test

  Global functioning according to Functioning Assessment Short-Test

  6 month follow up

Secondary Outcomes (1)

• Time to all-cause treatment failure

  Six months

Study Arms (2)

Clozapine

EXPERIMENTAL

Clozapine, P.O., flexible dose, for up to 6 months

Drug: Clozapine

Risperidone, olanzapine or quetiapine

ACTIVE COMPARATOR

Risperidone, olanzapine or quetiapine, according to clinical indication, flexible dose, for up to 6 months

Drug: Risperidone; Drug: Olanzapine; Drug: Quetiapine

Interventions

Clozapine DRUG

Flexible dosage, with up-titration according to standard schedules employed for schezophrenia

Also known as: Clozaril

Clozapine

Risperidone DRUG

Risperidone, in a flexible dosage

Also known as: Risperdal

Risperidone, olanzapine or quetiapine

Olanzapine DRUG

Olanzapine, flexible dosage

Also known as: Zyprexa

Risperidone, olanzapine or quetiapine

Quetiapine DRUG

Quetiapine, flexible dosage

Also known as: Seroquel

Risperidone, olanzapine or quetiapine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• DSM-IV Bipolar I Disorder;
• having had a mood episode within the preceding year; DSM-IV rapid cyclers will be permitted to participate in this study;
• males or females between 18 and 65 years of age;
• ongoing illness symptoms including significant functional impairment;
• documented history of treatment resistance, defined as persistent symptoms despite simultaneous, adequate treatment with at least two medications: one mood stabilizer (lithium or valproate) + antipsychotic OR two mood stabilizers (at least one of them being lithium or valproate).
• each patient must have a level of understanding sufficient to agree to all the tests required by the protocol and must sign an informed consent document

You may not qualify if:

• patients with onset of illness after age 40 or illness resulting from secondary causes
• women who are pregnant or breastfeeding, or not using adequate contraception
• unstable medical illnesses
• clinically significant abnormal laboratory tests
• current active alcohol or substance abuse
• severe personality disorders
• contraindication to the use of clozapine or previous treatment with clozapine

Sponsors & Collaborators

• Hospital de Clinicas de Porto Alegre: lead
• Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.: collaborator
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator

Study Sites (1)

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90540001, Brazil

RECRUITING

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Clozapine; Risperidone; Olanzapine; Quetiapine Fumarate

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals

Study Officials

• PEDRO V MAGALHAES, M.D., Ph.D.

  Hospital de Clínicas de Porto Alegre / Universidade Federal do Rio Grande do Sul

  PRINCIPAL INVESTIGATOR

Central Study Contacts

PEDRO V MAGALHAES, M.D., Ph.D.

CONTACT

+555191123773; pedromaga2@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: August 11, 2015
• First Posted: September 29, 2015
• Study Start: October 1, 2015
• Primary Completion: June 1, 2019
• Study Completion: December 1, 2020
• Last Updated: October 2, 2018

Record last verified: 2018-10

Locations

BR (1)