Bipolar DisorderPhase 3NCT00221975
Combination Therapy in Dual Diagnosis Bipolar Rapid Cycling
A Phase 3 study testing Divalproex, Lamotrigine and Lithium in people with Bipolar Disorder, run by University Hospitals Cleveland Medical Center at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 16 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Divalproex, Lamotrigine and Lithium
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 98 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2002to Dec 2007
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 65 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University Hospitals of Cleveland
Cleveland, Ohio, 44106
About this study
Official title: 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.
- Conditions
- Bipolar Disorder
- Being tested
- Divalproex, Lamotrigine, Lithium
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DivalproexDrug
Also called Depakote
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.
LamotrigineDrug
Also called 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.
LithiumDrug
Also called Eskalith
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).
| Study group | Role | What they receive |
|---|---|---|
| Lithium + Divalproex + Lamictal | Active comparator | 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. Receives: Drug: Divalproex; Drug: Lamotrigine; Drug: Lithium |
| Lithium + Divalproex + Placebo | Placebo comparator | 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. Receives: Drug: Divalproex; Drug: Lithium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients who experience a marked and persistent bimodal response
Measured: Phase 1: Baseline - Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startJul 2002
- Primary completionJun 2007
- Study completionDec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by University Hospitals Cleveland Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals Cleveland Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joseph Calabrese, MD, University Hospitals Cleveland Medical Center
- Investigators
- Keming Gao, MD, PhD, Principal investigator, Case Western Reserve University / University Hospitals of Cleveland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00221975
- Sponsor's protocol ID
- 02T 183
- Status last verified
- Dec 2014
- First submitted
- 13 Sep 2005
- Last updated
- 3 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gao K, Verduin ML, Kemp DE, Tolliver BK, Ganocy SJ, Elhaj O, Bilali S, Brady KT, Findling RL, Calabrese JR. Clinical correlates of patients with rapid-cycling bipolar disorder and a recent history of substance use disorder: a subtype comparison from baseline data of 2 randomized, placebo-controlled trials. J Clin Psychiatry. 2008 Jul;69(7):1057-63. doi: 10.4088/jcp.v69n0703.
PubMed 18588360
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Therapy in Dual Diagnosis Rapid Cycling Bipolar Disorder
- ClinicalTrials.gov ID
- NCT00221975
- Acronym / sponsor ID
- 02T 183
- Conditions
- Bipolar Disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- University Hospitals Cleveland Medical CenterUniversity, hospital or other
- Study start
- Jul 2002
- Primary completion
- Jun 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lithium + Divalproex + Lamictal | Active comparator | Drug: Divalproex, Drug: Lamotrigine, Drug: LithiumLithium 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. |
| Lithium + Divalproex + Placebo | Placebo comparator | Drug: Divalproex, Drug: LithiumLithium 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. |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DivalproexAlso: DepakoteOnce 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. | Drug | Lithium + Divalproex + Lamictal, Lithium + Divalproex + Placebo |
| LamotrigineAlso: LamictalLithium monotherapy was initiated at 450 mg once daily and titrated slowly over 3 weeks to a minimum blood level of 0.5 mEqlL. | Drug | Lithium + Divalproex + Lamictal |
| LithiumAlso: EskalithSubjects 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). | Drug | Lithium + Divalproex + Lamictal, Lithium + Divalproex + Placebo |
Primary outcome
Proportion of patients who experience a marked and persistent bimodal response
Time frame: Phase 1: Baseline - Week 16
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2014.
- Derived from this study: PubMed 18588360Gao K, Verduin ML, Kemp DE, Tolliver BK, Ganocy SJ, Elhaj O, Bilali S, Brady KT, Findling RL, Calabrese JR. Clinical correlates of patients with rapid-cycling bipolar disorder and a recent history of substance use disorder: a subtype comparison from baseline data of 2 randomized, placebo-controlled trials. J Clin Psychiatry. 2008 Jul;69(7):1057-63. doi: 10.4088/jcp.v69n0703.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keming Gao, MD, PhD principal investigator
Case Western Reserve University / University Hospitals of Cleveland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Divalproex, Lamotrigine and Lithium in people with Bipolar Disorder, run by University Hospitals Cleveland Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients who experience a marked and persistent bimodal response (time frame: Phase 1: Baseline - Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00221975, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2014.