Bipolar DisorderPhase 4Ram-TIMENCT00552760
Ramelteon for the Treatment of Insomnia and Mood Stability in Patients With Euthymic Bipolar Disorder
A Phase 4 study testing Ramelteon in people with Bipolar Disorder, run by Lehigh Valley Hospital at 1 site in United States.
Trial summary
The purpose of this study is to determine whether treating sleep difficulties in patients with bipolar disorder also improves their mood stability. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Ramelteon
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to May 2010
- Phase
- Phase 4
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of written informed consent before initiation of any study-related procedures
- Men and women aged 18 to 65 years.
- A documented clinical diagnosis according to the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision) meeting criteria 296.4x Bipolar I disorder, most recent episode manic, 296.6x Bipolar I disorder, most recent episode mixed, or 296.5x Bipolar I disorder, most recent episode depressed.
- PSQI total score of >=5.
- MADRS total score of <=12.
- YMRS total score of <= 12
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- Female patients of childbearing potential must have a negative urine pregnancy test at enrollment and be willing to use a reliable method of birth control, i.e., double-barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device or tubal ligation, during the study.
- Be able to understand and comply with the requirements of the study, as judged by the investigator.
- Outpatient status at enrollment.
Who cannot join
- Patients with a diagnosis of DSM-IV Axis II disorder which has a major impact on the patient's current psychiatric status.
- Presence of prohibited medications of antidepressants (including MAOI's) and systemic corticosteroids.
- Patients with a diagnosis of primary insomnia disorders
- Patients with a diagnosis of severe chronic obstructive pulmonary disease
- A clinical finding that is untreated (eg, hypertension, poorly controlled diabetes, angina) or that, in the opinion of the investigator, would be negatively affected by the study medication or that would affect the study medication.
- Patients with active substance abuse diagnoses (except tobacco abuse).
- Known history of intolerance or hypersensitivity to ramelteon or to any other component in the tablet.
Trial locations and contacts
1 site in 1 country.
United States1 site
Lehigh Valley Hospital, Department of Psychiatry
Allentown, Pennsylvania, 18103
About this study
Official title: A Double-Blind, Randomized, Placebo-Controlled Trial of Ramelteon for the Treatment of Insomnia and Mood Stability in Patients With Euthymic Bipolar Disorder.
The purpose of this study is to determine whether treating sleep difficulties in patients with bipolar disorder also improves their mood stability.
Read the detailed description
Patients with euthymic bipolar disorder, although free of significant mood symptoms, often have continued sleep disturbances. Improving patients' sleep by also normalizing the circadian rhythm will lead to fewer mood exacerbations. Ramelteon offers a new and more pharmacologically exact mechanism to re-synchronize the SCN. The administration of ramelteon for bipolar patients will improve sleep and will cause fewer mood exacerbations.
Patients with bipolar disorder often experience frequent mood alterations that are attempted to be controlled by mood stabilizing agents and anti-psychotic agents. Both classes of medications have numerous significant side effects. Establishing that ramelteon is helpful in the sleep of patients with bipolar disorder and helpful in mood stability will increase the number of treatment options for bipolar patients.
- Conditions
- Bipolar Disorder
- Being tested
- Ramelteon, 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.
RamelteonDrug
Also called Rozerem
one 8 mg tablet at bedtime for up to 6 months
PlaceboDrug
one tablet at bedtime for up to 6 months
| Study group | Role | What they receive |
|---|---|---|
| Ramelteon | Experimental | 8 mg Receives: Drug: Ramelteon |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pittsburgh Sleep Quality Index (PSQI) Global Score
Self-rated scale to measure quality of sleep via questions regarding sleep latency, duration, efficiency, disturbances, use of sleep medication, and daytime dysfunction. Scores range from 0-21, higher scores represent more significant sleep disturbance.
Measured: Monthly for 6 months
Secondary outcomes (4)
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
10-item, standardized, well-validated scale used to measure severity of depressive symptoms; sensitive to treatment effects in depressed outpatients. Scores range from 0-60, higher scores represent more severe depressive symptoms.
Measured: Monthly for 6 months
Young Mania Rating Scale (YMRS) Total Score
11-item standardized, well-validated scale used to measure manic symptoms; sensitive to treatment effects in manic patients. Scores range from 0-60, higher scores represent more severe manic symptoms.
Measured: Monthly for 6 months
Clinical Global Impressions Bipolar Version(CGI-BP) Severity of Illness Overall Score
3-part (mania, depression, overall bipolar illness), physician-administered scale used to assess global illness severity; used to measure change. Each part is rated from 1-7, higher scores represent more severe mental illness. Only overall bipolar rating was used.
Measured: Monthly for 6 months
Cumulative Proportion of Participants in Each Arm Surviving Without Relapse
Survival analysis techniques, including Kaplan Meier curves, were used to evaluate group differences in time to relapse. Relapse was defined as a medication initiation or change for manic/depressed/mixed symptoms, a hospitalization for manic/depressed/mixed symptoms, MADRS score >= 16, YMRS score > 14, and suicide risk or imminent risk of suicide. Time to relapse was measured discretely in terms of the number of assessment visits until discontinued from the study.
Measured: Monthly for 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2007 (estimated)
- Study startNov 2007
- Primary completionMar 2010
- Study completionMay 2010
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 (6)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lehigh Valley Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda
- Responsible party
- Principal investigator, Edward R. Norris, MD, Lehigh Valley Hospital
- Investigators
- Edward R. Norris, MD, Principal investigator, Lehigh Valley Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00552760
- Sponsor's protocol ID
- 07-006R
- Acronym
- Ram-TIME
- Status last verified
- Mar 2014
- First submitted
- 31 Oct 2007
- Last updated
- 14 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.
PubMed 2748771Dokucu ME, Yu L, Taghert PH. Lithium- and valproate-induced alterations in circadian locomotor behavior in Drosophila. Neuropsychopharmacology. 2005 Dec;30(12):2216-24. doi: 10.1038/sj.npp.1300764.
PubMed 15956996Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382-9. doi: 10.1192/bjp.134.4.382.
PubMed 444788Jones SH, Hare DJ, Evershed K. Actigraphic assessment of circadian activity and sleep patterns in bipolar disorder. Bipolar Disord. 2005 Apr;7(2):176-86. doi: 10.1111/j.1399-5618.2005.00187.x.
PubMed 15762859American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, CD, American Psychiatric Association, 2000.
Norris ER, Karen Burke, Correll JR, Zemanek KJ, Lerman J, Primelo RA, Kaufmann MW. A double-blind, randomized, placebo-controlled trial of adjunctive ramelteon for the treatment of insomnia and mood stability in patients with euthymic bipolar disorder. J Affect Disord. 2013 Jan 10;144(1-2):141-7. doi: 10.1016/j.jad.2012.06.023. Epub 2012 Sep 7.
PubMed 22963894
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Randomized, Placebo-Controlled Trial of Ramelteon for the Treatment of Insomnia and Mood Stability in Patients With Euthymic Bipolar Disorder.
- ClinicalTrials.gov ID
- NCT00552760
- Acronym / sponsor ID
- Ram-TIME / 07-006R
- Conditions
- Bipolar Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Lehigh Valley HospitalUniversity, hospital or other
- Collaborators
- Takeda
- Study start
- Nov 2007
- Primary completion
- Mar 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 2 Nov 2007 (estimated)
- Results
- Posted 5 Jul 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether treating sleep difficulties in patients with bipolar disorder also improves their mood stability.
Detailed description
Patients with euthymic bipolar disorder, although free of significant mood symptoms, often have continued sleep disturbances. Improving patients' sleep by also normalizing the circadian rhythm will lead to fewer mood exacerbations. Ramelteon offers a new and more pharmacologically exact mechanism to re-synchronize the SCN. The administration of ramelteon for bipolar patients will improve sleep and will cause fewer mood exacerbations.
Patients with bipolar disorder often experience frequent mood alterations that are attempted to be controlled by mood stabilizing agents and anti-psychotic agents. Both classes of medications have numerous significant side effects. Establishing that ramelteon is helpful in the sleep of patients with bipolar disorder and helpful in mood stability will increase the number of treatment options for bipolar patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ramelteon | Experimental | Drug: Ramelteon8 mg |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Provision of written informed consent before initiation of any study-related procedures
- Men and women aged 18 to 65 years.
- A documented clinical diagnosis according to the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision) meeting criteria 296.4x Bipolar I disorder, most recent episode manic, 296.6x Bipolar I disorder, most recent episode mixed, or 296.5x Bipolar I disorder, most recent episode depressed.
- PSQI total score of >=5.
- MADRS total score of <=12.
Key exclusion criteria (7 listed)
- Patients with a diagnosis of DSM-IV Axis II disorder which has a major impact on the patient's current psychiatric status.
- Presence of prohibited medications of antidepressants (including MAOI's) and systemic corticosteroids.
- Patients with a diagnosis of primary insomnia disorders
- Patients with a diagnosis of severe chronic obstructive pulmonary disease
- A clinical finding that is untreated (eg, hypertension, poorly controlled diabetes, angina) or that, in the opinion of the investigator, would be negatively affected by the study medication or that would affect the study medication.
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 |
|---|---|---|
| RamelteonAlso: Rozeremone 8 mg tablet at bedtime for up to 6 months | Drug | Ramelteon |
| Placeboone tablet at bedtime for up to 6 months | Drug | Placebo |
Primary outcome
Pittsburgh Sleep Quality Index (PSQI) Global Score
Time frame: Monthly for 6 months
Self-rated scale to measure quality of sleep via questions regarding sleep latency, duration, efficiency, disturbances, use of sleep medication, and daytime dysfunction. Scores range from 0-21, higher scores represent more significant sleep disturbance.
4 secondary outcomes
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Time frame: Monthly for 6 months
Young Mania Rating Scale (YMRS) Total Score
Time frame: Monthly for 6 months
Clinical Global Impressions Bipolar Version(CGI-BP) Severity of Illness Overall Score
Time frame: Monthly for 6 months
Cumulative Proportion of Participants in Each Arm Surviving Without Relapse
Time frame: Monthly for 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 2748771Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.
- Background: PubMed 15956996Dokucu ME, Yu L, Taghert PH. Lithium- and valproate-induced alterations in circadian locomotor behavior in Drosophila. Neuropsychopharmacology. 2005 Dec;30(12):2216-24. doi: 10.1038/sj.npp.1300764.
- Background: PubMed 444788Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382-9. doi: 10.1192/bjp.134.4.382.
- Background: PubMed 15762859Jones SH, Hare DJ, Evershed K. Actigraphic assessment of circadian activity and sleep patterns in bipolar disorder. Bipolar Disord. 2005 Apr;7(2):176-86. doi: 10.1111/j.1399-5618.2005.00187.x.
- BackgroundAmerican Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, CD, American Psychiatric Association, 2000.
- Results publication: PubMed 22963894Norris ER, Karen Burke, Correll JR, Zemanek KJ, Lerman J, Primelo RA, Kaufmann MW. A double-blind, randomized, placebo-controlled trial of adjunctive ramelteon for the treatment of insomnia and mood stability in patients with euthymic bipolar disorder. J Affect Disord. 2013 Jan 10;144(1-2):141-7. doi: 10.1016/j.jad.2012.06.023. Epub 2012 Sep 7.
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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.
Edward R. Norris, MD principal investigator
Lehigh Valley Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ramelteon in people with Bipolar Disorder, run by Lehigh Valley Hospital 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 9 inclusion and 7 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 14 Apr 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 5 Jul 2010). 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?
Pittsburgh Sleep Quality Index (PSQI) Global Score (time frame: Monthly for 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 NCT00552760, which also lists 6 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 14 Apr 2014.