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Asenapine in the Treatment of Older Adults With Bipolar Disorder

Primary Purpose

Bipolar Disorder

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Asenapine
Sponsored by
University Hospitals Cleveland Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bipolar Disorder

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects must have type I Bipolar disorder by DSM-IV criteria confirmed on the Mini Neuropsychiatric Interview (MINI)
  • Subjects must be age 60 or older

  • Subjects must have sub-optimal response to current psychotropic management including at least one of the following:

    1. Behaviors and symptoms of irritability, agitation, mood lability or diminished ability to interact with others in their place of residence
    2. Diminished ability to take care of basic personal needs in their place of residence due to symptoms of BD

Exclusion Criteria:

  • History of intolerance or resistance to asenapine
  • Clinical diagnosis of dementia or Mini-mental state (MMSE) < 24
  • History of TIA, stroke or MI within the past 12 months
  • Medical illness that is the clear, underlying etiology of BD
  • Unstable medical illness or condition including prolonged QT interval, which in the opinion of the study investigators, is likely to affect the outcome of the study or the subject's safety
  • DSM-IV substance dependence (except nicotine or caffeine) within the past 3 months.
  • Rapid cycling BD defined as 4 or more discrete mood episodes within the previous 12 months.
  • At high risk for self-harm or suicide

Sites / Locations

  • University Hospitals Case Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Asenapine

Arm Description

12-weeks of open-label asenapine treatment

Outcomes

Primary Outcome Measures

Change in Depressive Symptoms as Measured by the Hamilton Depression Rating Scale (HAM-D)
The minimum possible score is 0 and the maximum score is 52. A higher score implies a worse condition.
Change in Manic Symptoms as Measured by the Young Mania Rating Scale (YMRS)
The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.

Secondary Outcome Measures

Change in Global Psychopathology as Measured by the Clinical Global Impression Scale for Use in Bipolar Illness (CGI-BP)
The minimum possible score is 1 and the maximum score is 7. A higher score implies a worse condition. The CGI-BP has three scores - Mania Severity, Depression Severity, and Overall Bipolar Illness Severity.
Change in Perception of Physical Health as Measured by the Short Form General Health Survey (SF-12)
The minimum possible score is 1 and the maximum score is 99. A higher score implies a better perceived condition.
Change in Perception of Mental Health as Measured by the Short Form General Health Survey (SF-12)
The minimum possible score is 1 and the maximum score is 99. A higher score implies a better perceived condition.
Change in Depressive Symptoms as Measured by the Montgomery Asberg Depression Rating Scale (MADRS)
The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.
Change in Bipolar Disorder Symptoms as Measured by the Brief Psychiatric Rating Scale (BPRS)
The minimum possible score is 18 and the maximum score is 126. A higher score implies a worse condition.
Change in Cognitive Status as Measured by the Stroop Task
The Stroop evaluates patients for cognitive functioning. Patients are to read words aloud or name colors as quickly as possible in a 45-second period. The measure contains three tasks, each associated with a subscale as follows: Word, Color, and Color-Word. Each subscale contains 100 items. The raw score range for each of the subscales is 0-100. Each raw subscale score is converted to a T-Score. The possible T-Score range for the Word subscale is 15 to 85. The possible T-Score range for the Color subscale is 8 to 92. The possible T-Score range for the Color-Word subscale is 3 to 98. Higher scores on the subscales indicate better cognitive functioning. Subscales are scored independently and are not added to produce a total score.
Change in Cognitive Status as Measured by the Trail Making Test
The Trails test is a measure of cognitive functioning. The measure consists of two parts: A and B. In part A, participants are asked to draw a trail connecting a series of numbers in sequential order. In Part B, participants are asked to draw a trail connecting a combination of letters and numbers. The time taken to complete each task is noted as the score (e.g., 78 seconds). For Trails A, there is no upper limit on the score, as subjects are given as much time as is needed for them to complete the task. Higher scores indicate poorer cognitive functioning. In Trails B, the task is timed with an upper limit of five minutes. If, at four minutes, it is determined that the subject will not likely complete the task in the time allotted, then the task can be called off. Higher scores indicate poorer cognitive functioning.
Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT)
Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-36). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Total recall scores appear in this entry below.
Change in Cognitive Status as Measured by the Dementia Rating Scale (DRS)
The DRS contains items that evaluate cognitive function across 5 subscales: attention, initiation/perseveration, construction, conceptualization, and memory. Subscale raw score ranges are: attention (0-37), initiation/perseveration (0-37), construction (0-6), conceptualization (0-39), and memory (0-25). Raw subscale scores are added for a total raw score with range 0-144. For each raw subscale score, scaled scores are looked up from a battery of 13 tables. Age of the participant determines which table is to be used. Total raw subscale score also has its own scaled score in the tables. In addition to use in determining scaled scores for each of the subscales, these tables are used to look up the scaled score for the total raw score. The tables are contained in the article Robust and Expanded Norms for the Dementia Rating Scale (Pedraza, Lucas, et al. 2010); Archives of Clinical Neuropsychology 25; 347-358. Higher scores, raw and scaled, indicate better cognitive functioning.
World Health Organization Disability Assessment Scale (WHO-DAS)
The WHO-DAS II is used to assess patients for difficulties that they experience due to health conditions. Six subscales are represented which cover the following domains: Getting Around (range 1-10), Self Care (range 1-10), Life Activities (range 1-20), Understand/Communicate (range 1-10), Participation in Society (range 1-10), and Getting Along with People (range 1-10). Lower scores represent more positive outcomes, while higher scores represent worse outcomes. Total summary scores were not computed for our analyses and is optional for the measure.
Barnes Drug-induced Akathisia Rating Scale (BARS)
This scale is used to measure the presence of akathisia, as may result from use of certain psychotropic medications. The scale contains four items and the score for each item is added to produce the total score. Total scores range from 0 to 14. Higher scores indicate more adverse outcomes.
Assessment of Motor Control Abnormality as Measured by the Simpson Angus Scale (SAS)
The Simpson-Angus Scale is used to monitor for neurological and musculoskeletal side effects that may be a result of certain psychotropic medications. The scale consists of 10 questions which each can be rated on a scale of 0 to 4. Scores for each item are added to produce a total score. The highest possible total score is 40. Higher scores indicate more adverse outcomes.
Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT)
Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-12). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Delayed recall scores appear in this entry below.
Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT)
Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-12). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Retention scores appear in this entry below.
Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT)
Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-12). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Recognition Discrimination Index appears in this entry below

Full Information

First Posted
October 24, 2011
Last Updated
December 8, 2014
Sponsor
University Hospitals Cleveland Medical Center
Collaborators
Case Western Reserve University
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1. Study Identification

Unique Protocol Identification Number
NCT01460290
Brief Title
Asenapine in the Treatment of Older Adults With Bipolar Disorder
Official Title
Asenapine in the Treatment of Older Adults With Bipolar Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
October 2011 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
March 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospitals Cleveland Medical Center
Collaborators
Case Western Reserve University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Objectives: The investigators propose a first-ever, prospective trial of asenapine in older adults with bipolar disorder (BD) to evaluate effects on mood symptoms, tolerability and functional/general health status. Given the dearth of treatment data on older adults with BD, findings are likely to be of substantial clinical interest, may inform larger future studies and will assist in refining bipolar treatment recommendations. Hypotheses: Primary: Asenapine therapy will be associated with reduced bipolar manic and depressive symptoms in older adults with BD. Secondary: Asenapine therapy will be associated with improved functional and general health status, improved global psychopathology, and good tolerability in older adults with BD.

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
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Asenapine
Arm Type
Experimental
Arm Description
12-weeks of open-label asenapine treatment
Intervention Type
Drug
Intervention Name(s)
Asenapine
Other Intervention Name(s)
Saphris
Intervention Description
Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
Primary Outcome Measure Information:
Title
Change in Depressive Symptoms as Measured by the Hamilton Depression Rating Scale (HAM-D)
Description
The minimum possible score is 0 and the maximum score is 52. A higher score implies a worse condition.
Time Frame
Baseline and 12 weeks
Title
Change in Manic Symptoms as Measured by the Young Mania Rating Scale (YMRS)
Description
The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.
Time Frame
Baseline and 12 weeks
Secondary Outcome Measure Information:
Title
Change in Global Psychopathology as Measured by the Clinical Global Impression Scale for Use in Bipolar Illness (CGI-BP)
Description
The minimum possible score is 1 and the maximum score is 7. A higher score implies a worse condition. The CGI-BP has three scores - Mania Severity, Depression Severity, and Overall Bipolar Illness Severity.
Time Frame
Baseline and 12 weeks
Title
Change in Perception of Physical Health as Measured by the Short Form General Health Survey (SF-12)
Description
The minimum possible score is 1 and the maximum score is 99. A higher score implies a better perceived condition.
Time Frame
Baseline and 12 weeks
Title
Change in Perception of Mental Health as Measured by the Short Form General Health Survey (SF-12)
Description
The minimum possible score is 1 and the maximum score is 99. A higher score implies a better perceived condition.
Time Frame
Baseline and 12 weeks
Title
Change in Depressive Symptoms as Measured by the Montgomery Asberg Depression Rating Scale (MADRS)
Description
The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.
Time Frame
Baseline and 12 weeks
Title
Change in Bipolar Disorder Symptoms as Measured by the Brief Psychiatric Rating Scale (BPRS)
Description
The minimum possible score is 18 and the maximum score is 126. A higher score implies a worse condition.
Time Frame
Baseline and 12 weeks
Title
Change in Cognitive Status as Measured by the Stroop Task
Description
The Stroop evaluates patients for cognitive functioning. Patients are to read words aloud or name colors as quickly as possible in a 45-second period. The measure contains three tasks, each associated with a subscale as follows: Word, Color, and Color-Word. Each subscale contains 100 items. The raw score range for each of the subscales is 0-100. Each raw subscale score is converted to a T-Score. The possible T-Score range for the Word subscale is 15 to 85. The possible T-Score range for the Color subscale is 8 to 92. The possible T-Score range for the Color-Word subscale is 3 to 98. Higher scores on the subscales indicate better cognitive functioning. Subscales are scored independently and are not added to produce a total score.
Time Frame
Baseline and 12 weeks
Title
Change in Cognitive Status as Measured by the Trail Making Test
Description
The Trails test is a measure of cognitive functioning. The measure consists of two parts: A and B. In part A, participants are asked to draw a trail connecting a series of numbers in sequential order. In Part B, participants are asked to draw a trail connecting a combination of letters and numbers. The time taken to complete each task is noted as the score (e.g., 78 seconds). For Trails A, there is no upper limit on the score, as subjects are given as much time as is needed for them to complete the task. Higher scores indicate poorer cognitive functioning. In Trails B, the task is timed with an upper limit of five minutes. If, at four minutes, it is determined that the subject will not likely complete the task in the time allotted, then the task can be called off. Higher scores indicate poorer cognitive functioning.
Time Frame
Baseline and 12 weeks
Title
Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT)
Description
Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-36). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Total recall scores appear in this entry below.
Time Frame
Baseline and 12 weeks
Title
Change in Cognitive Status as Measured by the Dementia Rating Scale (DRS)
Description
The DRS contains items that evaluate cognitive function across 5 subscales: attention, initiation/perseveration, construction, conceptualization, and memory. Subscale raw score ranges are: attention (0-37), initiation/perseveration (0-37), construction (0-6), conceptualization (0-39), and memory (0-25). Raw subscale scores are added for a total raw score with range 0-144. For each raw subscale score, scaled scores are looked up from a battery of 13 tables. Age of the participant determines which table is to be used. Total raw subscale score also has its own scaled score in the tables. In addition to use in determining scaled scores for each of the subscales, these tables are used to look up the scaled score for the total raw score. The tables are contained in the article Robust and Expanded Norms for the Dementia Rating Scale (Pedraza, Lucas, et al. 2010); Archives of Clinical Neuropsychology 25; 347-358. Higher scores, raw and scaled, indicate better cognitive functioning.
Time Frame
Baseline and 12 weeks
Title
World Health Organization Disability Assessment Scale (WHO-DAS)
Description
The WHO-DAS II is used to assess patients for difficulties that they experience due to health conditions. Six subscales are represented which cover the following domains: Getting Around (range 1-10), Self Care (range 1-10), Life Activities (range 1-20), Understand/Communicate (range 1-10), Participation in Society (range 1-10), and Getting Along with People (range 1-10). Lower scores represent more positive outcomes, while higher scores represent worse outcomes. Total summary scores were not computed for our analyses and is optional for the measure.
Time Frame
12 weeks
Title
Barnes Drug-induced Akathisia Rating Scale (BARS)
Description
This scale is used to measure the presence of akathisia, as may result from use of certain psychotropic medications. The scale contains four items and the score for each item is added to produce the total score. Total scores range from 0 to 14. Higher scores indicate more adverse outcomes.
Time Frame
Baseline and 12 weeks
Title
Assessment of Motor Control Abnormality as Measured by the Simpson Angus Scale (SAS)
Description
The Simpson-Angus Scale is used to monitor for neurological and musculoskeletal side effects that may be a result of certain psychotropic medications. The scale consists of 10 questions which each can be rated on a scale of 0 to 4. Scores for each item are added to produce a total score. The highest possible total score is 40. Higher scores indicate more adverse outcomes.
Time Frame
Baseline and 12 weeks
Title
Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT)
Description
Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-12). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Delayed recall scores appear in this entry below.
Time Frame
Baseline and 12 weeks
Title
Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT)
Description
Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-12). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Retention scores appear in this entry below.
Time Frame
Baseline and 12 weeks
Title
Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT)
Description
Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-12). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Recognition Discrimination Index appears in this entry below
Time Frame
Baseline and 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must have type I Bipolar disorder by DSM-IV criteria confirmed on the Mini Neuropsychiatric Interview (MINI) Subjects must be age 60 or older Subjects must have sub-optimal response to current psychotropic management including at least one of the following: Behaviors and symptoms of irritability, agitation, mood lability or diminished ability to interact with others in their place of residence Diminished ability to take care of basic personal needs in their place of residence due to symptoms of BD Exclusion Criteria: History of intolerance or resistance to asenapine Clinical diagnosis of dementia or Mini-mental state (MMSE) < 24 History of TIA, stroke or MI within the past 12 months Medical illness that is the clear, underlying etiology of BD Unstable medical illness or condition including prolonged QT interval, which in the opinion of the study investigators, is likely to affect the outcome of the study or the subject's safety DSM-IV substance dependence (except nicotine or caffeine) within the past 3 months. Rapid cycling BD defined as 4 or more discrete mood episodes within the previous 12 months. At high risk for self-harm or suicide
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martha Sajatovic, M.D.
Organizational Affiliation
University Hospitals Cleveland Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospitals Case Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States

12. IPD Sharing Statement

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Asenapine in the Treatment of Older Adults With Bipolar Disorder

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