Bipolar DisorderPhase 3NCT00063362
Combination Therapy for the Treatment of Bipolar Disorders
A Phase 3 study testing Lithium, Lamotrigine and Divalproex in people with Bipolar Disorder, run by University Hospitals Cleveland Medical Center.
Trial summary
This study will compare triple and double drug regimens in the treatment of patients with depression, hypomania, or mania. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Lithium, Lamotrigine and Divalproex
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- No sites listed yet
- Study dates
- Feb 2002to Jul 2007
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Bipolar I or II Disorder
- Meet criteria for rapid cycling, defined as four or more episodes over the past 12 months
- Meet criteria for a major depressive episode
Who cannot join
- History of intolerability of lithium, divalproex, or lamotrigine
About this study
Official title: Combination Therapy in Bipolar Rapid Cycling
This study will compare triple and double drug regimens in the treatment of patients with depression, hypomania, or mania.
Read the detailed description
Early studies have shown lithium to produce a high percentage of satisfactory clinical response in patients with bipolar disorders. These studies, however, do not include lithium-refractory subgroups, such as bipolar II disorder patients. When the wide spectrum of bipolar disorders is considered, the lithium response rate decreases significantly. More broadly effective regimens are needed.
Participants in this study will be randomly assigned to receive either lithium plus divalproex or lithium, divalproex, and lamotrigine for 7 months. Symptoms of depression and mania will be assessed with scales and patient questionnaires.
- Conditions
- Bipolar Disorder
- Being tested
- Lithium, Lamotrigine, Divalproex, Placebo
- Keywords
- Depression
- Medical subject headings
- Bipolar Disorder, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LithiumDrug
Also called Lithium Carbonate
Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 milliequivalent /L (mEq/L).
LamotrigineDrug
Also called Lamictal
Patients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum dose of 200 mg per day.
DivalproexDrug
Also called Depakote, Valproic Acid
Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL.
PlaceboDrug
Patients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum dose of 200 mg per day.
| Study group | Role | What they receive |
|---|---|---|
| Lithium + divalproex + lamotrigine | Experimental | Not described Receives: Drug: Lithium; Drug: Lamotrigine; Drug: Divalproex |
| Lithium + divalproex + placebo | Placebo comparator | Not described Receives: Drug: Lithium; Drug: Divalproex; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Proportion of Patients Who Experience a Marked and Persistent Bimodal Response
A marked bimodal response is defined by the following three conditions over four consecutive weeks while on triple therapy and after three weeks of ltg:
- Montgomery Asberg Depression Rating Scale (MADRS) total score of <= 19
- Young Mania Rating Scale (YMRS) total score of <= 12.5
- Global Assessment Scale (GAS) score >= 51
The MADRS measures the severity of a subject's depression symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe depression.
The YMRS measures the severity of a subject's manic symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe mania.
The GAS measures a used to rate subjectively the social, occupational, and psychological functioning of a subject and ranges in score from 0-100, with a higher score indicating better social, occupational, and psychological functioning.
Measured: Baseline and Week 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2003 (estimated)
- Study startFeb 2002
- Primary completionJul 2007
- Study completionJul 2007
Why it stopped: Funding Expiration
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals Cleveland Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Keming Gao, 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
- NCT00063362
- Sponsor's protocol ID
- R21MH062650
- Other IDs
- R21MH062650, DSIR AT-SO
- Status last verified
- Oct 2016
- First submitted
- 25 Jun 2003
- Last updated
- 7 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Therapy in Bipolar Rapid Cycling
- ClinicalTrials.gov ID
- NCT00063362
- Acronym / sponsor ID
- R21MH062650
- Conditions
- Bipolar Disorder
- Keywords
- Depression
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding Expiration
- Enrolment
- 49 participants (actual)
- Lead sponsor
- University Hospitals Cleveland Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Feb 2002
- Primary completion
- Jul 2007 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 27 Jun 2003 (estimated)
- Results
- Posted 30 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will compare triple and double drug regimens in the treatment of patients with depression, hypomania, or mania.
Detailed description
Early studies have shown lithium to produce a high percentage of satisfactory clinical response in patients with bipolar disorders. These studies, however, do not include lithium-refractory subgroups, such as bipolar II disorder patients. When the wide spectrum of bipolar disorders is considered, the lithium response rate decreases significantly. More broadly effective regimens are needed.
Participants in this study will be randomly assigned to receive either lithium plus divalproex or lithium, divalproex, and lamotrigine for 7 months. Symptoms of depression and mania will be assessed with scales and patient questionnaires.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lithium + divalproex + lamotrigine | Experimental | Drug: Lithium, Drug: Lamotrigine, Drug: Divalproex |
| Lithium + divalproex + placebo | Placebo comparator | Drug: Lithium, Drug: Divalproex, Drug: Placebo |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Bipolar I or II Disorder
- Meet criteria for rapid cycling, defined as four or more episodes over the past 12 months
- Meet criteria for a major depressive episode
Key exclusion criteria (1 listed)
- History of intolerability of lithium, divalproex, or lamotrigine
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 |
|---|---|---|
| LithiumAlso: Lithium CarbonateLithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 milliequivalent /L (mEq/L). | Drug | Lithium + divalproex + lamotrigine, Lithium + divalproex + placebo |
| LamotrigineAlso: LamictalPatients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum dose of 200 mg per day. | Drug | Lithium + divalproex + lamotrigine |
| DivalproexAlso: Depakote, Valproic AcidDivalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL. | Drug | Lithium + divalproex + lamotrigine, Lithium + divalproex + placebo |
| PlaceboPatients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum dose of 200 mg per day. | Drug | Lithium + divalproex + placebo |
Primary outcome
The Proportion of Patients Who Experience a Marked and Persistent Bimodal Response
Time frame: Baseline and Week 28
A marked bimodal response is defined by the following three conditions over four consecutive weeks while on triple therapy and after three weeks of ltg: 1. Montgomery Asberg Depression Rating Scale (MADRS) total score of <= 19 2. Young Mania Rating Scale (YMRS) total score of <= 12.5 3. Global Assessment Scale (GAS) score >= 51 The MADRS measures the severity of a subject's depression symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe depression. The YMRS measures the severity of a subject's manic symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe mania. The GAS measures a used to rate subjectively the social, occupational, and psychological functioning of a subject and ranges in score from 0-100, with a higher score indicating better social, occupational, and psychological functioning.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lithium, Lamotrigine and Divalproex in people with Bipolar Disorder, run by University Hospitals Cleveland Medical Center.
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 3 inclusion and 1 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: stopped early, as of the sponsor's last update on 7 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
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?
Yes. Results are posted in the registry (first posted 30 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
The Proportion of Patients Who Experience a Marked and Persistent Bimodal Response (time frame: Baseline and Week 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Nov 2016.