Open Label Study of Lithium Plus Extended-Release Carbamazepine (ERC-CBZ) for Rapid Cycling Bipolar Disorder
Information source: Creighton University
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Bipolar Disorder
Intervention: Lithium Plus Extended- Release Carbamazepine (Drug)
Phase: Phase 4
Status: Active, not recruiting
Sponsored by: Creighton University Official(s) and/or principal investigator(s):
Sriram Ramaswamy, M.D., Principal Investigator, Affiliation: Creighton University
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.
Clinical Details
Official title: Open Label Prophylaxis Study of Lithium Plus Extended- Release Carbamazepine (Equetro®) Combination for Rapid Cycling Bipolar Disorder
Study design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Primary outcome: 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.
Secondary outcome: 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
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
Minimum age: 19 Years.
Maximum age: 65 Years.
Gender(s): Both.
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.
Locations and Contacts
Creighton University Department of Psychiatry, Omaha, Nebraska 68131, United States
Additional Information
Starting date: May 2006
Ending date: March 2008
Last updated: December 13, 2007
|
