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Open Label Study of Lithium Plus Extended-Release Carbamazepine (ERC-CBZ) for Rapid Cycling Bipolar Disorder
This study is ongoing, but not recruiting participants.
First Received: May 10, 2006   Last Updated: December 13, 2007   History of Changes
Sponsor: Creighton University
Collaborator: Shire Pharmaceutical Development
Information provided by: Creighton University
ClinicalTrials.gov Identifier: NCT00325286
  Purpose

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.


Condition Intervention Phase
Bipolar Disorder
Drug: Lithium Plus Extended- Release Carbamazepine
Phase IV

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Official Title: Open Label Prophylaxis Study of Lithium Plus Extended- Release Carbamazepine (Equetro®) Combination for Rapid Cycling Bipolar Disorder

Resource links provided by NLM:


Further study details as provided by Creighton University:

Primary Outcome Measures:
  • The primary efficacy measure will be the time to relapse. Relapse will determined by; need for additional pharmacotherapy, hospitalization for an affective episode, increase of >/= 50% in HAM-D and YMRS scores. [ Time Frame: Patients will be seen weekly during preliminary phase and biweekly during the open label phase ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: Patients will be seen weekly during the preliminary phase and biweekly during the open label phase ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: May 2006
Estimated Study Completion Date: March 2008
Arms Assigned Interventions
1: Experimental
Treatment with lithium and extended release carbamazepine
Drug: 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

  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   19 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00325286

Locations
United States, Nebraska
Creighton University Department of Psychiatry
Omaha, Nebraska, United States, 68131
Sponsors and Collaborators
Creighton University
Shire Pharmaceutical Development
Investigators
Principal Investigator: Sriram Ramaswamy, M.D. Creighton University
  More Information

No publications provided

Responsible Party: Creighton University ( Sriram Ramaswamy, M.D., Assistant Professor of Psychiatry )
Study ID Numbers: 05-13934
Study First Received: May 10, 2006
Last Updated: December 13, 2007
ClinicalTrials.gov Identifier: NCT00325286     History of Changes
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Psychotropic Drugs
Affective Disorders, Psychotic
Pathologic Processes
Sensory System Agents
Mental Disorders
Therapeutic Uses
Analgesics
Lithium
Antidepressive Agents
Disease
Tranquilizing Agents
Bipolar Disorder
Lithium Carbonate
Central Nervous System Depressants
Enzyme Inhibitors
Antimanic Agents
Antipsychotic Agents
Pharmacologic Actions
Carbamazepine
Analgesics, Non-Narcotic
Mood Disorders
Peripheral Nervous System Agents
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on November 25, 2009