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Pilot Study of Levetiracetam (Keppra® (Registered Trademark)) for Bipolar Illness

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ClinicalTrials.gov Identifier: NCT00015769
Recruitment Status : Completed
First Posted : May 7, 2001
Last Update Posted : March 4, 2008
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)

Tracking Information
First Submitted Date  ICMJE May 4, 2001
First Posted Date  ICMJE May 7, 2001
Last Update Posted Date March 4, 2008
Study Start Date  ICMJE April 2001
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00015769 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Study of Levetiracetam (Keppra® (Registered Trademark)) for Bipolar Illness
Official Title  ICMJE Pilot Evaluation of Levetiracetam (Keppra® (Registered Trademark)) in Bipolar Illness
Brief Summary

This study will explore the possible effectiveness of levetiracetam in patients with bipolar illness who have not responded adequately to standard treatments. Levetiracetam was recently approved to treat seizures. Other drugs in the same class as levetiracetam, including carbamazepine and valproate, are widely recognized as substitute medications for lithium or are used as an adjunct to it, and other anticonvulsants have also shown promise in improving bipolar symptoms.

Patients with bipolar illness whose manic, depressed or unstable moods are not adequately controlled by their current treatment and who have not responded previously to two standard treatments (i.e., lithium, valproate, carbamazepine or neuroleptics) may be eligible for this study.

Participants will take levetiracetam starting at 500 mg daily. If this dose is well tolerated, it will be increased to 500 mg twice a day. Every 3 days, doses may be increased until the target dose of 3000 mg/day is reached. Higher doses, not to exceed 4000 mg/day, may be tried in patients who do not respond fully to the lower doses. Patients and observers will use standard ratings to evaluate the patients' response to therapy during the 8-week study. If, after 8 weeks, the results appear promising, patients may continue treatment for an additional 6 months to evaluate longer-term effects.

Detailed Description

Almost all of the approved anticonvulsant compounds (with the exception of gabapentin and tiagabine) have now been suggested to have acute antimanic or more long-term mood stabilizing properties. Carbamazepine and valproate have gained a widely recognized role in treatment algorithms of bipolar illness, and lamotrigine has shown promising antidepressant effects. Levetiracetam (Keppra® (Registered Trademark)) is the most recently approved anti-epileptic drug available, and deserves pilot exploration in bipolar illness for a variety of reasons. These include: its positive side-effects profile; it is a derivative of the nootropic agent piracetam which has memory-enhancing properties in animal studies; it likely has a unique mechanism of action since it is not active on most of the traditional excitatory and inhibitory neurotransmitter systems; it is not active on traditional anticonvulsant models such as pentylenetetrazol (PTZ) or maximum electroshock (MES) seizures, but is able to stop both the development and completed phase of amygdala-kindled seizures; and it is not metabolized by hepatic enzymes and thus has few adverse pharmacokinetic interactions.

We propose pilot exploration of levetiracetam as an adjunctive agent in patients with bipolar illness who are inadequately responsive to routine psychopharmacological agents for bipolar illness. At the NIMH we will study a maximum of 10 acutely depressed, 10 manic, and 10 cycling patients enrolled in Protocol 97-M-0039. We would start at Levetiracetam doses of 500 mg/day, and not to exceed 4000 mg/day. Response will be based primarily on the percentage of patients showing "much" or "very much" improvement on the GCI-BP score in each of the three groups as augmented by the percentage decrement on cross-sectional scales such as the Inventory of Depressive Symptomatology (IDS) and Young Mania Rating Scale (YMRS) in conjunction with prospective ratings on the NIMH-LCMp. Should preliminary evidence of efficacy be observed in this open add-on clinical trial, more systematic controlled studies will then be designed for confirmation of promising target areas of efficacy.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE Bipolar Disorder
Intervention  ICMJE Drug: levetiracetam
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE
 (submitted: June¬†23,¬†2005)
30
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE April 2003
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

INCLUSION CRITERIA:

Patients meeting DSM -IV criteria for bipolar I, bipolar II, bipolar NOS, and schizoaffective illness-bipolar type will be eligible for study. They will be enrolled in approved Protocol #97-M-0039 and thus will not have H.I.V. and will have provided consent for all of the rating forms utilized in this study.

Patients with inadequate response to two standard agents (i.e., lithium, valproate, carbamazepine, or neuroleptics) in the treatment of bipolar illness will be eligible for open adjunctive levetiracetam.

If serum creatinine is above normal, a creatinine clearance will be preformed; this must be above 85 in order for a patient to be eligible for this study.

EXCLUSION CRITERIA:

Women of child-bearing age who are not on an active method of birth control or who are likely to become pregnant will be excluded.

Men or women with significant renal disease will also be excluded.

For the depressed phase, patients will have an IDS score of 18 or greater, an LCM depression score of low moderate or greater, and a GCI-BP severity score of moderate or greater for more than 2 weeks, i.e., the DSM-IV durational criteria.

For the hypomanic/manic phase, patients will have an YMRS score of 8 or greater, an LCM mania rating of mild or greater, and a CGI-BP severity score of moderately ill or greater for 7 days or more.

Those in the cycling group would meet the severity criteria for depression and mania. They would have four or more mood "switches," and have an overall illness rating on the CGI-BP severity score of moderate or greater.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00015769
Other Study ID Numbers  ICMJE 010168
01-M-0168
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE National Institute of Mental Health (NIMH)
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date April 2003

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP