Bipolar DisorderPhase 3NCT00194129
Lithium and Divalproex for the Treatment of Comorbid Rapid Cycling Bipolar Disorder and Substance Abuse Disorder
A Phase 3 study testing Lithium and Divalproex in people with Bipolar Disorder, run by University Hospitals Cleveland Medical Center at 1 site in United States.
Trial summary
This study will determine the efficacy and safety of combination therapy with divalproex and lithium for treating mania in people with rapid cycling bipolar disorder and a substance abuse disorder. Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Lithium and Divalproex
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 1997to Sep 2006
- 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 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- To be included in this study, patients will be required to be either acutely hypomanic or manic as defined by the Diagnostic and Statistical Manual -IV (DSM-IV) and meet criteria for current substance abuse and/or dependence disorder within the last six months.
- Must have 4 or more episodes in the immediate 12 months prior to study entry.
- Males or females 16 - 65 years of age.
- A score of 60 or less on the Global Assessment Scale.
- Have no medical illness precluding the use of lithium or divalproex.
Who cannot join
- Patients who have had intolerable side effects to lithium levels 0.8 meq/L or divalproex levels of 50 ug/ml. Patients who have been completely non-responsive to lithium in the past will be excluded, whereas patients who have had partial responses to lithium will be permitted into the study.
- Patients with a prior history of seizure disorder, cerebral vascular disease, structural brain damage from trauma, clinically significant focal neurological abnormalities, EEG abnormalities with frank paroxysmal activity or a previous CT/MRI scan of the brain with gross structural abnormalities.
- Patients who require anticoagulant drug therapy.
- Patients who have uncontrolled gastrointestinal, renal, hepatic, endocrine, cardiovascular, pulmonary, immunological or hematological disease. Patients with alcohol-related liver disease as reflected by diffuse elevations in liver functions tests exceeding the upper limits of the normal range by 50% will be excluded.
- Patients who are pregnant or plan to become pregnant during the study.
- Patients who have received haloperidol decanoate or fluphenazine decanoate within the last 10 weeks.
Show all 9Show fewer
- Patients who have a central nervous system (CNS) neoplasm, uncontrolled metabolic, demyelinating or progressive disorder; active CNS infection; or any progressive neurological disorder.
- Patients who are taking exogenous steroids.
- Patients who do not meet criteria for substance abuse or dependence.
Trial locations and contacts
1 site in 1 country.
United States1 site
University Hospitals of Cleveland
Cleveland, Ohio, 44106
About this study
Official title: A Randomized, Double Blind Comparison of Lithium Monotherapy Versus Lithium Plus Divalproex for the Outpatient Management of Hypomania/Mania in Patients With Rapid Cycling Bipolar Disorder Comorbid With Substance Abuse/Dependence
This study will determine the efficacy and safety of combination therapy with divalproex and lithium for treating mania in people with rapid cycling bipolar disorder and a substance abuse disorder.
Read the detailed description
Longitudinal Evaluation of the Efficacy and Safety of Divalproex and Lithium 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 are initially stabilized on dual therapy of lithium and depakote and then randomly assigned to double-blind treatment with either lithium monotherapy or continued dual therapy. Patients remain in the study for six months or until they experience a relapse. Patients in this study are required to bring a friend or family member to all study visits as well as attend chemical dependency services. This study is sponsored by the NIMH. Subjects receive study-related care at no cost.
- Conditions
- Bipolar Disorder
- Being tested
- Lithium, Divalproex, Placebo
- Medical subject headings
- Bipolar Disorder
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 300 mg twice daily and titrated over 3-6 weeks to minimum blood levels of 0.8 meq/L.
DivalproexDrug
Also called Valproic Acid, Depakote
Divalproex was then initiated at 250 mg twice daily and increased over 3-6 weeks to minimum blood levels of 50 ug/ml.
PlaceboDrug
Placebo pills that looked exact to divaloproex were provided to subjects and take twice daily.
| Study group | Role | What they receive |
|---|---|---|
| Lithium plus Divalproex | Experimental | Patients assigned to the combination group were continued on lithium and blinded divalproex. Receives: Drug: Lithium; Drug: Divalproex |
| Lithium plus placebo | Placebo comparator | Patients assigned to lithium monotherapy underwent divalproex-placebo substitution at a rate of 250 mg decrements every week until discontinued. Receives: Drug: Lithium; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Treatment for Emerging Symptoms of a Mood Relapse
A relapse is a return to either a depressive, manic, hypomanic or mixed episode after a period of not have any symptoms.
Measured: Up to 6 months
Secondary outcomes (5)
Time to Treatment for Emerging Symptoms of a Manic/Hypomanic/Mixed Episode
Measured: Up to 6 months
Time to Treatment for Emerging Symptoms of a Depressive Episode
Measured: Up to 6 months
Change in Rate of Alcohol Use Disorders After Open-label Treatment With Lithium and Divalproex
Number of subjects who no longer met criteria for active abuse or had entered into early full remission after receiving up to 6 months of open-label treatment with lithium and divalproex
Measured: Baseline to Month 6
Change in Rate of Cannabis Use Disorders After Open-label Treatment With Lithium and Divalproex
Number of subjects who no longer met criteria for active cannabis abuse or had entered into early full remission after receiving up to 6 months of open-label treatment with lithium and divalproex
Measured: Baseline to Month 6
Change in Rate of Cocaine Use Disorders After Open-label Treatment With Lithium and Divalproex
Number of subjects who no longer met criteria for active cocaine abuse or had entered into early full remission after receiving up to 6 months of open-label treatment with lithium and divalproex
Measured: Baseline to Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2005 (estimated)
- Study startNov 1997
- Primary completionSep 2006
- Study completionSep 2006
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.
- Publications (2)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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 31 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), Abbott
- Responsible party
- Principal investigator, Joseph Calabrese, MD, University Hospitals Cleveland Medical Center
- Investigators
- Joseph R Calabrese, MD, Principal investigator, Case Western Reserve University / University Hospitals of Cleveland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00194129
- Sponsor's protocol ID
- R01MH050165
- Other IDs
- R01MH050165
- Status last verified
- Jan 2018
- First submitted
- 13 Sep 2005
- Last updated
- 20 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kemp DE, Gao K, Ganocy SJ, Elhaj O, Bilali SR, Conroy C, Findling RL, Calabrese JR. A 6-month, double-blind, maintenance trial of lithium monotherapy versus the combination of lithium and divalproex for rapid-cycling bipolar disorder and Co-occurring substance abuse or dependence. J Clin Psychiatry. 2009 Jan;70(1):113-21. doi: 10.4088/jcp.07m04022. Epub 2008 Dec 30.
PubMed 19192457Gao 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 20 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind Comparison of Lithium Monotherapy Versus Lithium Plus Divalproex for the Outpatient Management of Hypomania/Mania in Patients With Rapid Cycling Bipolar Disorder Comorbid With Substance Abuse/Dependence
- ClinicalTrials.gov ID
- NCT00194129
- Acronym / sponsor ID
- R01MH050165
- Conditions
- Bipolar Disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University Hospitals Cleveland Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), Abbott
- Study start
- Nov 1997
- Primary completion
- Sep 2006 (actual)
- Study completion
- Sep 2006 (actual)
- First posted
- 19 Sep 2005 (estimated)
- Results
- Posted 23 Dec 2013
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 determine the efficacy and safety of combination therapy with divalproex and lithium for treating mania in people with rapid cycling bipolar disorder and a substance abuse disorder.
Detailed description
Longitudinal Evaluation of the Efficacy and Safety of Divalproex and Lithium 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 are initially stabilized on dual therapy of lithium and depakote and then randomly assigned to double-blind treatment with either lithium monotherapy or continued dual therapy. Patients remain in the study for six months or until they experience a relapse. Patients in this study are required to bring a friend or family member to all study visits as well as attend chemical dependency services. This study is sponsored by the NIMH. Subjects receive study-related care at no cost.
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 plus Divalproex | Experimental | Drug: Lithium, Drug: DivalproexPatients assigned to the combination group were continued on lithium and blinded divalproex. |
| Lithium plus placebo | Placebo comparator | Drug: Lithium, Drug: PlaceboPatients assigned to lithium monotherapy underwent divalproex-placebo substitution at a rate of 250 mg decrements every week until discontinued. |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- To be included in this study, patients will be required to be either acutely hypomanic or manic as defined by the Diagnostic and Statistical Manual -IV (DSM-IV) and meet criteria for current substance abuse and/or dependence disorder within the last six months.
- Must have 4 or more episodes in the immediate 12 months prior to study entry.
- Males or females 16 - 65 years of age.
- A score of 60 or less on the Global Assessment Scale.
- Have no medical illness precluding the use of lithium or divalproex.
Key exclusion criteria (9 listed)
- Patients who have had intolerable side effects to lithium levels 0.8 meq/L or divalproex levels of 50 ug/ml. Patients who have been completely non-responsive to lithium in the past will be excluded, whereas patients who have had partial responses to lithium will be permitted into the study.
- Patients with a prior history of seizure disorder, cerebral vascular disease, structural brain damage from trauma, clinically significant focal neurological abnormalities, EEG abnormalities with frank paroxysmal activity or a previous CT/MRI scan of the brain with gross structural abnormalities.
- Patients who require anticoagulant drug therapy.
- Patients who have uncontrolled gastrointestinal, renal, hepatic, endocrine, cardiovascular, pulmonary, immunological or hematological disease. Patients with alcohol-related liver disease as reflected by diffuse elevations in liver functions tests exceeding the upper limits of the normal range by 50% will be excluded.
- Patients who are pregnant or plan to become pregnant during the study.
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 300 mg twice daily and titrated over 3-6 weeks to minimum blood levels of 0.8 meq/L. | Drug | Lithium plus Divalproex, Lithium plus placebo |
| DivalproexAlso: Valproic Acid, DepakoteDivalproex was then initiated at 250 mg twice daily and increased over 3-6 weeks to minimum blood levels of 50 ug/ml. | Drug | Lithium plus Divalproex |
| PlaceboPlacebo pills that looked exact to divaloproex were provided to subjects and take twice daily. | Drug | Lithium plus placebo |
Primary outcome
Time to Treatment for Emerging Symptoms of a Mood Relapse
Time frame: Up to 6 months
A relapse is a return to either a depressive, manic, hypomanic or mixed episode after a period of not have any symptoms.
5 secondary outcomes
Time to Treatment for Emerging Symptoms of a Manic/Hypomanic/Mixed Episode
Time frame: Up to 6 months
Time to Treatment for Emerging Symptoms of a Depressive Episode
Time frame: Up to 6 months
Change in Rate of Alcohol Use Disorders After Open-label Treatment With Lithium and Divalproex
Time frame: Baseline to Month 6
Change in Rate of Cannabis Use Disorders After Open-label Treatment With Lithium and Divalproex
Time frame: Baseline to Month 6
Change in Rate of Cocaine Use Disorders After Open-label Treatment With Lithium and Divalproex
Time frame: Baseline to Month 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 19192457Kemp DE, Gao K, Ganocy SJ, Elhaj O, Bilali SR, Conroy C, Findling RL, Calabrese JR. A 6-month, double-blind, maintenance trial of lithium monotherapy versus the combination of lithium and divalproex for rapid-cycling bipolar disorder and Co-occurring substance abuse or dependence. J Clin Psychiatry. 2009 Jan;70(1):113-21. doi: 10.4088/jcp.07m04022. Epub 2008 Dec 30.
- 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.
Joseph R Calabrese, MD 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 Lithium and Divalproex 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 5 inclusion and 9 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 20 Feb 2018. 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?
Yes. Results are posted in the registry (first posted 23 Dec 2013). 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?
Time to Treatment for Emerging Symptoms of a Mood Relapse (time frame: Up to 6 months). 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 NCT00194129, which also lists 2 linked publications.
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 20 Feb 2018.