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

Primary Purpose

Bipolar Disorder

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ramelteon
Placebo
Sponsored by
Lehigh Valley Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bipolar Disorder

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Lehigh Valley Hospital, Department of Psychiatry

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ramelteon

Placebo

Arm Description

8 mg

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
October 31, 2007
Last Updated
March 17, 2014
Sponsor
Lehigh Valley Hospital
Collaborators
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT00552760
Brief Title
Ramelteon for the Treatment of Insomnia and Mood Stability in Patients With Euthymic Bipolar Disorder
Acronym
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.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
November 2007 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
May 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Lehigh Valley Hospital
Collaborators
Takeda

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
90 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ramelteon
Arm Type
Experimental
Arm Description
8 mg
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Ramelteon
Other Intervention Name(s)
Rozerem
Intervention Description
one 8 mg tablet at bedtime for up to 6 months
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
one tablet at bedtime for up to 6 months
Primary Outcome Measure Information:
Title
Pittsburgh Sleep Quality Index (PSQI) Global Score
Description
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.
Time Frame
Monthly for 6 months
Secondary Outcome Measure Information:
Title
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Description
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.
Time Frame
Monthly for 6 months
Title
Young Mania Rating Scale (YMRS) Total Score
Description
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.
Time Frame
Monthly for 6 months
Title
Clinical Global Impressions Bipolar Version(CGI-BP) Severity of Illness Overall Score
Description
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.
Time Frame
Monthly for 6 months
Title
Cumulative Proportion of Participants in Each Arm Surviving Without Relapse
Description
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.
Time Frame
Monthly for 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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. Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edward R. Norris, MD
Organizational Affiliation
Lehigh Valley Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lehigh Valley Hospital, Department of Psychiatry
City
Allentown
State/Province
Pennsylvania
ZIP/Postal Code
18103
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
2748771
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.
Results Reference
background
PubMed Identifier
15956996
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.
Results Reference
background
PubMed Identifier
444788
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.
Results Reference
background
PubMed Identifier
15762859
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.
Results Reference
background
Citation
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, CD, American Psychiatric Association, 2000.
Results Reference
background
PubMed Identifier
22963894
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.
Results Reference
result

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

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