- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00029458
Clozapine for Treatment-Resistant Mania
A Double Blind Study Examining the Efficacy of Clozapine and a Study of the Pathophysiology in Treatment Resistant Mania
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.
Study Overview
Detailed Description
Study Type
Enrollment
Phase
- Phase 2
Contacts and Locations
Study Locations
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Maryland
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Bethesda, Maryland, United States, 20892
- National Institute of Mental Health (NIMH)
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
INCLUSION CRITERIA:
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.
EXCLUSION CRITERIA:
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;
General MRI exclusion criteria.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
Collaborators and Investigators
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Study Completion
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Bipolar and Related Disorders
- Bipolar Disorder
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Serotonin Agents
- Serotonin Antagonists
- GABA Agents
- GABA Antagonists
- Clozapine
Other Study ID Numbers
- 020085
- 02-M-0085
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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