- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00221975
Combination Therapy in Dual Diagnosis Bipolar Rapid Cycling
December 1, 2014 updated by: Joseph Calabrese, MD, University Hospitals Cleveland Medical Center
Combination Therapy in Dual Diagnosis Rapid Cycling Bipolar Disorder
Combination Therapy in Dual Diagnosis Bipolar Rapid Cycling: This study recruits males and females age 18 and older who currently meet diagnostic criteria for rapid cycling bipolar disorder (type I or II) and who have met the criteria for substance abuse or dependence of cocaine, marijuana and/or alcohol within the past six months.
Patients begin treatment with a combination of lithium and divalproex.
Once these medications are tolerated, they are randomly assigned to double-blind treatment with lamotrigine or placebo.
Patients remain in this study until they experience a marked bimodal response for four consecutive weeks.
This study is sponsored by the Stanley Foundation.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
98
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ohio
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Cleveland, Ohio, United States, 44106
- University Hospitals of Cleveland
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 65 years (Child, Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Has given written informed consent.
- Males or females 16 years of age and older. For patients less than 18 years old, concurrent written informed consent will also be required from the parents or legal guardians.
- Must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depression at the time of study entry.
- Must meet DSM-IV criteria for rapid-cycling bipolar disorder in the last 12 months.
- Must meet DSM-IV criteria for alcohol or drug abuse within the past 3 months or dependence in the last 6 months (unless most recent period of abstinence occurred while in a controlled environment).
- Must have no medical illness precluding the use of lithium, divalproex sodium and/or lamotrigine.
- Regardless of treatment response, patients who have been exposed to lithium or divalproex sodium will be included as long as the medication was adequately tolerated and all three medications were not administered concurrently.
Exclusion Criteria:
- Patients who have had intolerable side effects to lamotrigine, lithium at levels of 0.6 mEq/L or divalproex sodium at levels of 50ug/ml.
- Patients who have previously been treated with lithium, divalproex sodium and lamotrigine concurrently.
- Patients who have previously been treated with an adequate trial of lamotrigine, which was considered to be a treatment failure.
- Patients who do not have a recent history of, or are not currently abusing or dependent on alcohol or drugs.
- Patients with a prior history of seizure disorder, cerebral vascular disease, structural brain damage from trauma, clinically significant focal neurological abnormalities, closed head injury, EEG abnormalities with frank paroxysmal activity or a previous CT/MRI scan of the brain with gross structural abnormalities.
- Patients who have clinically significant gastrointestinal, renal, hepatic, endocrine, cardiovascular, pulmonary, immunologic, hematologic, or oncologic diseases. Clinically significant evidence of thyroid failure will be defined as a decreased free thyroxine index with several clinical signs and symptoms of overt failure.
- Patients who are pregnant, at-risk of becoming pregnant or intend to become pregnant during the study. Patients who are not at risk of becoming pregnant are females who are post menopausal, who have undergone a hysterectomy, bilateral oophorectomy or sterilization, who agree to use an IUD, barrier protection, a contraceptive implantation system (e.g., Norplant), oral contraceptive pills, or who, in the investigator's judgment, will continue to be sexually inactive.
- Patients who have received haloperidol decanoate or fluphenazine decanoate within the last 10 weeks.
- Patients who have a central nervous system (CNS) neoplasm, uncontrolled metabolic, demyelinating or progressive degenerative disorder, active CNS infection, or any progressive neurological disorder.
- Patients who are taking exogenous steroids.
- Patients who have ultra-fast rapid-cycling bipolar disorder, but do not formally meet DSM-IV criteria for bipolar disorder. This is designed to exclude patients with episode frequencies too high to permit objective quantification.
- Patients who are currently suicidal in the opinion of the investigator or have a score of greater than 4 on the suicide item of the (Montgomery-Asberg Rating Scale (MADRS).
- Patients who have been treated with any dose or duration of a tricyclic antidepressant within the last three months.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Lithium + Divalproex + Lamictal
Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over 3 weeks to a minimum blood level of 0.5 mEqlL.
Divalproex was then initiated at 250 mg twice daily and increased slowly over 5 weeks to a minimum blood level of 50 μg/mL.
Patients meeting the criteria of being non-responsive to lithium plus divalproex were randomly assigned to receive lamotrigine or placebo.
Patients randomized to the lamotrigine group were titrated up to a minimum dose of 150 mg and maximum dose of 200 mg per day.
|
Once a therapeutic blood level of lithium was achieved, Divalproex was initiated at 250 mg twice daily and increased slowly over 5 weeks to a minimum blood level of 50 μg/mL.
Other Names:
Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over 3 weeks to a minimum blood level of 0.5 mEqlL.
Other Names:
Subjects who did not respond to the combination of Lithium and Divalproex were then randomly assigned in a 1:1 ratio to adjunctive lamotrigine versus placebo after stratification by illness type (bipolar I versus bipolar II), historical response to lithium (response versus oon-response), and the length of current exposure to the combination treatment with lithium and divalproex (<2 months versus ≥2 months).
Other Names:
|
Placebo Comparator: Lithium + Divalproex + Placebo
Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over 3 weeks to a minimum blood level of 0.5 mEqlL.
Divalproex was then initiated at 250 mg twice daily and increased slowly over 5 weeks to a minimum blood level of 50 μg/mL.
Patients meeting the criteria of being non-responsive to lithium plus divalproex were randomly assigned to receive lamotrigine or placebo.
Patients randomized to the placebo group were giving matching placebo.
|
Once a therapeutic blood level of lithium was achieved, Divalproex was initiated at 250 mg twice daily and increased slowly over 5 weeks to a minimum blood level of 50 μg/mL.
Other Names:
Subjects who did not respond to the combination of Lithium and Divalproex were then randomly assigned in a 1:1 ratio to adjunctive lamotrigine versus placebo after stratification by illness type (bipolar I versus bipolar II), historical response to lithium (response versus oon-response), and the length of current exposure to the combination treatment with lithium and divalproex (<2 months versus ≥2 months).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Proportion of patients who experience a marked and persistent bimodal response
Time Frame: Phase 1: Baseline - Week 16
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Phase 1: Baseline - Week 16
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2002
Primary Completion (Actual)
June 1, 2007
Study Completion (Actual)
December 1, 2007
Study Registration Dates
First Submitted
September 13, 2005
First Submitted That Met QC Criteria
September 16, 2005
First Posted (Estimate)
September 22, 2005
Study Record Updates
Last Update Posted (Estimate)
December 3, 2014
Last Update Submitted That Met QC Criteria
December 1, 2014
Last Verified
December 1, 2014
More Information
Terms related to this study
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
- Enzyme Inhibitors
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Membrane Transport Modulators
- GABA Agents
- Anticonvulsants
- Sodium Channel Blockers
- Antimanic Agents
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Lamotrigine
- Valproic Acid
Other Study ID Numbers
- 02T 183
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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