NCT00029458

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of clozapine as a treatment for the manic phase of bipolar disorder. A significant proportion of manic patients either do not respond adequately to conventional treatment or cannot tolerate the adverse effects associated with therapeutic doses of these agents. Clozapine may be a safe and effective treatment for mania. However, the efficacy of clozapine as an alternative therapy in treatment-resistant bipolar disorder mania has not been extensively researched. The study will be conducted in three phases. Phase 1 is a screening phase that will take place for 2 to 7 days. Participants will undergo a baseline positron emission tomography (PET) scan of the brain at the end of this period. In Phase 2, participants will be randomly assigned to receive either clozapine or placebo (an inactive pill) for 3 weeks. They may also receive lorazepam for the first 10 days of Phase 2. After 3 weeks, patients treated with clozapine will undergo a second PET scan. During Phase 3, participants who received placebo and did not improve will be offered clozapine for 3 weeks. Those who received clozapine and did not improve will receive other treatment for 3 weeks. At the end of Phase 3, participants who were treated with clozapine will have another PET scan.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
42

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jan 2002

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2002

Completed
10 days until next milestone

First Submitted

Initial submission to the registry

January 11, 2002

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 14, 2002

Completed
3.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2005

Completed
Last Updated

March 4, 2008

Status Verified

October 1, 2005

First QC Date

January 11, 2002

Last Update Submit

March 3, 2008

Conditions

Bipolar Disorder

Keywords

Placebo ControlledAtypical Anti-PsychoticBipolar Mood DisorderPositron Emission TomographyDopamine Receptor BlockadeAntimanicManiaPathophysiologyTreatment-ResistantMood DisorderBPDBipolar

Interventions

ClozapineDRUG

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Males or females 18 to 65 years of age;
  • Diagnosis: DSM-IV Bipolar I Disorder, current episode manic or mixed with or without psychotic features as determined by SCID-P. This criteria includes the following diagnoses: 296.4X, Bipolar I Disorder, Most Recent Episode Manic, and 296.6X, Bipolar I Disorder, Most Recent Episode Mixed;
  • YMRS greater than or equal to 20 at Visits 1 and 2;
  • No decrease in total score of YMRS of greater than or equal to 20% during washout (between Visits 1 and 2);
  • Meet criteria for treatment resistance.
  • Patients must have experienced at least two manic or mixed episodes within five years prior to study entry; DSM-IV rapid cyclers will be permitted to participate in this study;
  • Each patient must have a level of understanding sufficient to agree to all the tests required by the protocol;
  • Each patient must understand the nature of the study and must sign an informed consent document. Before participating in this study, we will advise all patients to complete a NIH Advance Directive Form. However, completing a NIH Advanced Directive form is not a requirement for participating in this study.
  • Previous lack of response (during a manic episode) to any two of the following antimanic agents: lithium, valproate, carbamazepine, oxcarbazepine, typical antipsychotic drug, or atypical antipsychotic drug (olanzapine, risperidone, ziprasidone, aripiprazole, quetiapine). If the subject has only taking one of these antimanic treatments, then the research physician may start one of them at NIH. Subjects not responding to a 3 week trial of an antimanic agent of their choice (at least a 50% decrease on the YMRS rating scale form baseline) will be eligible to be randomized if they continue to meet study criteria.

You may not qualify if:

  • WBC count is less than 3500/mm(3) or history of a myeloproliferative disorder.
  • History of meeting criteria for DSM-IV criteria for schizophrenia or other psychotic disorder;
  • History of DSM-IV substance abuse or dependence, including alcohol within the last four weeks;
  • Acute or unstable medical illnesses, (e.g., delirium, metastatic cancer, unstable diabetes, decompensated cardiac, hepatic, renal or pulmonary disease, or stroke or myocardial infarction within the last six months);
  • Current pregnancy or plan to become pregnant during the first three months (the duration of the study) in woman of childbearing age; breast-feeding in woman with infants;
  • Previous treatment with clozapine;
  • History of seizures;
  • History of leukopenia or agranulocytosis;
  • Uncorrected hypo- or hyperthyroidism;
  • Clinically significant abnormal laboratory tests;
  • Concomitant use carbamazepine or other concomitant medication with primarily CNS activity; Has received an investigational drug within 30 days of enrollment.
  • Has received an antidepressant within 4 weeks prior to Visit 1 (8 weeks for fluoxetine);
  • No course of ECT (electroconvulsive therapy) within the preceding 4 weeks to Visit 1;
  • Treatment with an injectable depot neuroleptic within less than one dosing interval prior to Visit 1;
  • Has an acute or chronic illness likely to impair drug absorption, distribution, metabolism or excretion;

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institute of Mental Health (NIMH)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

  • Ahlfors UG, Baastrup PC, Dencker SJ, Elgen K, Lingjaerde O, Pedersen V, Schou M, Aaskoven O. Flupenthixol decanoate in recurrent manic-depressive illness. A comparison with lithium. Acta Psychiatr Scand. 1981 Sep;64(3):226-37. doi: 10.1111/j.1600-0447.1981.tb00778.x.

    PMID: 7324992BACKGROUND

  • Altshuler LL, Bartzokis G, Grieder T, Curran J, Mintz J. Amygdala enlargement in bipolar disorder and hippocampal reduction in schizophrenia: an MRI study demonstrating neuroanatomic specificity. Arch Gen Psychiatry. 1998 Jul;55(7):663-4. doi: 10.1001/archpsyc.55.7.663. No abstract available.

    PMID: 9672058BACKGROUND

  • American Psychiatric Association Practice Guidelines. Practice guideline for the treatment of patients with borderline personality disorder. American Psychiatric Association. Am J Psychiatry. 2001 Oct;158(10 Suppl):1-52. No abstract available.

    PMID: 11665545BACKGROUND

MeSH Terms

Conditions

Bipolar DisorderManiaMood Disorders

Interventions

Clozapine

Condition Hierarchy (Ancestors)

Bipolar and Related DisordersMental DisordersNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

DibenzazepinesHeterocyclic Compounds, 3-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Design

Study Type
interventional
Phase
phase 2
Purpose
TREATMENT
Sponsor Type
NIH

Study Record Dates

First Submitted

January 11, 2002

First Posted

January 14, 2002

Study Start

January 1, 2002

Study Completion

October 1, 2005

Last Updated

March 4, 2008

Record last verified: 2005-10

Locations

US(1)