Open Label Study of Lithium Plus Extended-Release Carbamazepine (ERC-CBZ) for Rapid Cycling Bipolar Disorder

NCT ID: NCT00325286

Last Updated: 2007-12-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2008-03-31

Brief Summary

This is an open label design using Lithium plus extended release carbamazepine (Equetro) in combination for 6 months. Rapid cycling bipolar disorder is frequently treatment refractory and associated with repeated hospitalizations and complications. The results of this study will offer a promising approach to treat this complex disorder. The primary efficacy measure will be the time to relapse. Relapse will determined by the investigator based on the following: Need for additional pharmacotherapy for mood-related symptoms, hospitalization for an mood episode, increase of more than 50% in HAM-D and YMRS scores from the baseline visit.

Detailed Description

Open label Design with Lithium plus Extended release carbamazepine combination for 6 months. Extended release carbamazepine at doses of 1600 mg/day will be utilized. Lithium dosage will be adjusted to maintain therapeutic blood levels.

Patient Population: N = 20.

Primary and Secondary Efficacy Endpoints:

The primary efficacy measure will be the time to relapse. Relapse will determined by the investigator based on the following

• Need for additional pharmacotherapy for affective symptoms
• Hospitalization for an affective episode
• Increase of more than 50% in HAM-D and YMRS scores from baseline

The differences in the frequency of affective episodes in the 6-month prior to the treatment with ERC-CBZ and 6 months after treatment initiation will also be measured. Secondary efficacy measures will include; changes in the 17- Item Hamilton Depression Scale (HAM-D), Young Mania Rating Scale (YMRS), Clinical Global Severity Scale (CGI -S), Clinical Global Improvement Scale (CGI-I) scores at baseline and scores during treatment with ERC-CBZ.

Inclusion Criteria:

1. Subjects, 19 years and older with DSM-IV defined Bipolar Disorder with a history of the rapid cycling within the past 12 months.

2. Subjects may be either in a manic, mixed or depressive phase at time of study entry.

3. Subjects must be on lithium therapy for 6 months or longer. Stable lithium therapy will be defined as: No changes in lithium dosage for at least 2 weeks prior to study entry and a therapeutic lithium level (0.6 to 1.2 mEq) prior to study entry.

Exclusion Criteria:

1. Subjects with a lifetime history of Schizophrenia or Schizoaffective Disorder

2. If patients are on thyroid replacement therapy they have to on stable doses for the past 3 months at study enrollment.

3. Presence of active suicide ideations or score of > 3 on the suicide subscale of the 17 - item HAM-D.

4. Current substance dependence (excluding nicotine) defined as no dependence criteria for 30 days prior to study enrollment

5. Subjects with a history of non-response to carbamazepine or lithium

6. Subjects who are pregnant or planning to become pregnant

7. Subjects with a history of allergic/idiosyncratic reaction or intolerability to carbamazepine or lithium.

Study Procedures:

Preliminary Phase: The Structured Clinical Interview Diagnostic Schedule (SCID), medical & psychiatric history and baseline laboratory testing, EKG; pregnancy test will be obtained to ensure study eligibility. Eligible subjects will receive ERC-CBZ at starting doses ranging from 100 to 200 mg b.i.d. depending on clinical presentation and further titration up to a maximum dose of 1600 mg/day will be done at the discretion of the investigator. This titration phase will not extend beyond 2 weeks during which changes in concomitant medications will be allowed. Next, all psychotropics excluding lithium, ERC-CBZ and benzodiazepines will be tapered over a 2-week period. During the preliminary phase subjects will be seen weekly and assessments will be made using the HAM-D, YMRS, CGI -S, CGI-I, AE, and Concomitant medications

Open Label Phase: Subjects on lithium and ERC-CBZ therapy will enter this phase for 6 months. Changes to both lithium and ERC-CBZ will be permitted during this phase with serum levels to guide titration. Use of lorazepam, as a rescue medication will be permitted. Study visits will be every biweekly for 6 months. The HAM-D, YMRS and CGI-S, CGI-I, AE, concomitant medications will be assessed at each visit. Compliance will be assessed by pill counts at each study visit.

Conditions

Bipolar Disorder

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Treatment with lithium and extended release carbamazepine

Group Type: EXPERIMENTAL

Lithium Plus Extended- Release Carbamazepine

Intervention Type: DRUG

Preliminary phase subjects receive ERC-CBZ starting dose range from 100 to 200 mg b.i.d. and further titration up to a maximum dose of 1600 mg/day done at the discretion of the investigator. Titration phase will not extend beyond 2 weeks.Open label phase subjects stabilized on lithium and ERC-CBZ therapy will enter this phase for 6 months

Interventions

Lithium Plus Extended- Release Carbamazepine

Preliminary phase subjects receive ERC-CBZ starting dose range from 100 to 200 mg b.i.d. and further titration up to a maximum dose of 1600 mg/day done at the discretion of the investigator. Titration phase will not extend beyond 2 weeks.Open label phase subjects stabilized on lithium and ERC-CBZ therapy will enter this phase for 6 months

Intervention Type: DRUG

Other Intervention Names

Epitol, Tegretol

Eligibility Criteria

Inclusion Criteria

1. Subjects, 19 years and older with DSM-IV defined Bipolar Disorder with a history of the rapid cycling within the past 12 months.

2. Subjects may be either in a manic, mixed or depressive phase at time of study entry.

3. Subjects must be on lithium therapy for 6 months or longer. Stable lithium therapy will be defined as: No changes in lithium dosage for at least 2 weeks prior to study entry and a therapeutic lithium level (0.6 to 1.2 mEq) prior to study entry.

Exclusion Criteria

1. Subjects with a lifetime history of Schizophrenia or Schizoaffective Disorder

2. If patients are on thyroid replacement therapy they have to on stable doses for the past 3 months at study enrollment.

3. Presence of active suicide ideations or score of > 3 on the suicide subscale of the 17 - item HAM-D.

4. Current substance dependence (excluding nicotine) defined as no dependence criteria for 30 days prior to study enrollment

5. Subjects with a history of non-response to carbamazepine or lithium

6. Subjects who are pregnant or planning to become pregnant

7. Subjects with a history of allergic/idiosyncratic reaction or intolerability to carbamazepine or lithium.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: collaborator

Creighton University

OTHER

Sponsor Role: lead

Responsible Party

Creighton University

Principal Investigators

Sriram Ramaswamy, M.D.

Role: PRINCIPAL_INVESTIGATOR

Creighton University

Locations

Creighton University Department of Psychiatry

Omaha, Nebraska, United States

Countries

United States

Other Identifiers

05-13934

Identifier Type: -

Identifier Source: org_study_id