Clinical trial NCT00552760: Ramelteon for the Treatment of Insomnia and Mood Stability in Patients With Euthymic Bipolar Disorder
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bipolar Disorder
Lead sponsor: Lehigh Valley Hospital
Sponsor class: OTHER
Collaborators: name: Takeda
First posted: 2007-11-02
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pittsburgh Sleep Quality Index (PSQI) Global Score
timeFrame: Monthly for 6 months
Secondary outcomes:
measure: Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Monthly for 6 months
measure: Young Mania Rating Scale (YMRS) Total Score
timeFrame: Monthly for 6 months
measure: Clinical Global Impressions Bipolar Version(CGI-BP) Severity of Illness Overall Score
timeFrame: Monthly for 6 months
measure: Cumulative Proportion of Participants in Each Arm Surviving Without Relapse
timeFrame: Monthly for 6 months
Other outcomes:
Locations:
city: Allentown
country: United States
facility: Lehigh Valley Hospital, Department of Psychiatry
state: Pennsylvania
Study officials:
affiliation: Lehigh Valley Hospital
name: Edward R. Norris, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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. doi: 10.1038/sj.npp.1300764.
citation: Montgomery 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.
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. doi: 10.1111/j.1399-5618.2005.00187.x.
citation: American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, CD, American Psychiatric Association, 2000.
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 Affect Disord. 2013 Jan 10;144(1-2):141-7. doi: 10.1016/j.jad.2012.06.023. Epub 2012 Sep 7.