Ramelteon for the Treatment of Insomnia and Mood Stability in Patients With Euthymic Bipolar Disorder

Bipolar Disorder Clinical Trial

— Ram-TIME  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00552760
• Other study ID #: 07-006R
• Status: Completed
• Phase: Phase 4
• First received: October 31, 2007
• Last updated: March 17, 2014
• Start date: November 2007
• Est. completion date: May 2010

Study information

• Verified date: March 2014
• Source: Lehigh Valley Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether treating sleep difficulties in patients with bipolar disorder also improves their mood stability.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: May 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Provision of written informed consent before initiation of any study-related procedures

2. Men and women aged 18 to 65 years.

3. 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.

4. PSQI total score of >=5.

5. MADRS total score of <=12.

6. YMRS total score of <= 12

7. 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.

8. Be able to understand and comply with the requirements of the study, as judged by the investigator.

9. Outpatient status at enrollment.

Exclusion Criteria:

1. Patients with a diagnosis of DSM-IV Axis II disorder which has a major impact on the patient's current psychiatric status.

2. Presence of prohibited medications of antidepressants (including MAOI's) and systemic corticosteroids.

3. Patients with a diagnosis of primary insomnia disorders

4. Patients with a diagnosis of severe chronic obstructive pulmonary disease

5. 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.

6. Patients with active substance abuse diagnoses (except tobacco abuse).

7. Known history of intolerance or hypersensitivity to ramelteon or to any other component in the tablet.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Drug:
• Ramelteon
one 8 mg tablet at bedtime for up to 6 months
• Placebo
one tablet at bedtime for up to 6 months

Locations

Country	Name	City	State
United States	Lehigh Valley Hospital, Department of Psychiatry	Allentown	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Lehigh Valley Hospital	Takeda

Country where clinical trial is conducted

United States, 

References & Publications (6)

American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, CD, American Psychiatric Association, 2000.

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. — View Citation

Dokucu ME, Yu L, Taghert PH. Lithium- and valproate-induced alterations in circadian locomotor behavior in Drosophila. Neuropsychopharmacology. 2005 Dec;30(12):2216-24. — View Citation

Jones SH, Hare DJ, Evershed K. Actigraphic assessment of circadian activity and sleep patterns in bipolar disorder. Bipolar Disord. 2005 Apr;7(2):176-86. — View Citation

Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382-9. — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Monthly for 6 months	No
Secondary	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.	Monthly for 6 months	No
Secondary	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.	Monthly for 6 months	No
Secondary	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.	Monthly for 6 months	No
Secondary	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.	Monthly for 6 months	No