Ramelteon for the Treatment of Insomnia and Mood Stability in Patients With Euthymic Bipolar Disorder (Ram-TIME)

This study has been completed.
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
Edward R. Norris, MD, Lehigh Valley Hospital
ClinicalTrials.gov Identifier:
NCT00552760
First received: October 31, 2007
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Bipolar Disorder
Drug: Ramelteon
Drug: Placebo
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Lehigh Valley Hospital:

Primary Outcome Measures:
  • Pittsburgh Sleep Quality Index (PSQI) Global Score [ Time Frame: Monthly for 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Monthly for 6 months ] [ Designated as safety issue: No ]
    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.

  • Young Mania Rating Scale (YMRS) Total Score [ Time Frame: Monthly for 6 months ] [ Designated as safety issue: No ]
    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.

  • Clinical Global Impressions Bipolar Version(CGI-BP) Severity of Illness Overall Score [ Time Frame: Monthly for 6 months ] [ Designated as safety issue: No ]
    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.

  • Cumulative Proportion of Participants in Each Arm Surviving Without Relapse [ Time Frame: Monthly for 6 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 90
Study Start Date: November 2007
Study Completion Date: May 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ramelteon
8 mg
Drug: Ramelteon
one 8 mg tablet at bedtime for up to 6 months
Other Name: Rozerem
Placebo Comparator: Placebo Drug: Placebo
one tablet at bedtime for up to 6 months

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00552760

Locations
United States, Pennsylvania
Lehigh Valley Hospital, Department of Psychiatry
Allentown, Pennsylvania, United States, 18103
Sponsors and Collaborators
Lehigh Valley Hospital
Takeda
Investigators
Principal Investigator: Edward R. Norris, MD Lehigh Valley Hospital
  More Information

Publications:
Responsible Party: Edward R. Norris, MD, Physician-Investigator, Lehigh Valley Hospital
ClinicalTrials.gov Identifier: NCT00552760     History of Changes
Other Study ID Numbers: 07-006R
Study First Received: October 31, 2007
Results First Received: May 29, 2010
Last Updated: March 17, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders

ClinicalTrials.gov processed this record on July 22, 2014