Trial Outcomes & Findings for Bipolar Disorder in Late Life (NCT NCT00787930)

NCT ID: NCT00787930

Last Updated: 2014-07-31

Results Overview

Subject with acute mania were treated for 3 weeks with STEP-BD protocol using valproic acid as the primary intervention. Subject MRI's were evaluated for the presence of deep white matter hyperintensities (DWM) (\>2 on the the Boyko Classification). Boyko lesion classification system assesses DWM hyperintensities as follows: 0 = absent, 1 = punctate, 2 = rounded \<5 mm, 3 = irregular \>5 mm, 4 = confluent lesions.

Recruitment status

COMPLETED

Target enrollment

19 participants

Primary outcome timeframe

3 weeks

Results posted on

2014-07-31

Participant Flow

Patients were recruited from 2005-2009 from the inpatient units and Duke University Medical Center and John Umstead Hospital and the outpatient clinics at DUMC.

Only subjects currently in a manic episode were recruited for the acute treatment protocol substudy.

Participant milestones

Participant milestones
Measure
Naturalistic Treatment
Acutely manic subjects were treated using the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) expert consensus guidelines beginning with valproic acid (titrated to therapeutic levels) over a three week period. If there was a non-response to this intervention, then a subject would continue acute treatment using other interventions indicated by STEP-BD protocols. After stabilization, subjects were followed monthly up to a year's duration and treated using the STEP-BD expert consensus guidelines.
Acute Treatment -- 3 Weeks
STARTED
19
Acute Treatment -- 3 Weeks
COMPLETED
19
Acute Treatment -- 3 Weeks
NOT COMPLETED
0
Continuation Treatment -- up to 12 Month
STARTED
19
Continuation Treatment -- up to 12 Month
COMPLETED
16
Continuation Treatment -- up to 12 Month
NOT COMPLETED
3

Reasons for withdrawal

Reasons for withdrawal
Measure
Naturalistic Treatment
Acutely manic subjects were treated using the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) expert consensus guidelines beginning with valproic acid (titrated to therapeutic levels) over a three week period. If there was a non-response to this intervention, then a subject would continue acute treatment using other interventions indicated by STEP-BD protocols. After stabilization, subjects were followed monthly up to a year's duration and treated using the STEP-BD expert consensus guidelines.
Continuation Treatment -- up to 12 Month
Withdrawal by Subject
3

Baseline Characteristics

Bipolar Disorder in Late Life

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Naturalistic Treatment
n=19 Participants
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
15 Participants
n=5 Participants
Age, Categorical
>=65 years
4 Participants
n=5 Participants
Age, Continuous
49.68 years
STANDARD_DEVIATION 17.84 • n=5 Participants
Sex: Female, Male
Female
14 Participants
n=5 Participants
Sex: Female, Male
Male
5 Participants
n=5 Participants
Region of Enrollment
United States
19 participants
n=5 Participants

PRIMARY outcome

Timeframe: 3 weeks

Population: All subjects in an acute manic state who were treated with specified protocol.

Subject with acute mania were treated for 3 weeks with STEP-BD protocol using valproic acid as the primary intervention. Subject MRI's were evaluated for the presence of deep white matter hyperintensities (DWM) (\>2 on the the Boyko Classification). Boyko lesion classification system assesses DWM hyperintensities as follows: 0 = absent, 1 = punctate, 2 = rounded \<5 mm, 3 = irregular \>5 mm, 4 = confluent lesions.

Outcome measures

Outcome measures
Measure
Responders to Acute Treatment
n=10 Participants
Subjects in an acute manic episode who responded to treatment as measured by a Young Mania Rating Scale (YMRS) \<15 by week 3, which was the protocol-defined determination point for response to treatment.
Non-Responders to Acute Treatment
n=9 Participants
Subjects in an acute manic episode who did not respond to treatment as measured by a YMRS \>15 by week 3.
Boyko DWM Hyperintensity Value >2 in Subjects Who Received Acute Treatment for Mania
10 participants
9 participants

PRIMARY outcome

Timeframe: 12 months

Population: Subjects who completed at least 4-12 months of consistent follow up appointments after stabilization from an acute manic episode. Note that 3 subjects dropped out of continuation treatment.

Subject were evaluated for relapse of their mood disorder and for the presence of DWM Hyperintensities (\>2 on the the Boyko Classification. Boyko lesion classification system assesses DWM hyperintensities as follows: 0 = absent, 1 = punctate, 2 = rounded \<5 mm, 3 = irregular \>5 mm, 4 = confluent lesions. Subjects were also assessed for relapse, as defined by the Montgomery-Asberg Depression Rating Scale (MADRS)and the Young Mania Rating Scale (YMRS). Relapse was defined by protocol as either a MADRS scale \>15 or a YMRS scale \>15.

Outcome measures

Outcome measures
Measure
Responders to Acute Treatment
n=9 Participants
Subjects in an acute manic episode who responded to treatment as measured by a Young Mania Rating Scale (YMRS) \<15 by week 3, which was the protocol-defined determination point for response to treatment.
Non-Responders to Acute Treatment
n=7 Participants
Subjects in an acute manic episode who did not respond to treatment as measured by a YMRS \>15 by week 3.
Boyko DWM Hyperintensity Value >2 in Subjects Who Received Continuation Treatment
4 participants
4 participants

SECONDARY outcome

Timeframe: up to 12 months

Population: Number of subjects who who had \>2 on the DWM hyperintensity assessment from the Boyko classification system.

Subject were evaluated for relapse of their mood disorder and for the presence of subcortical (SC) Hyperintensities (\>2 on the the Boyko Classification). Boyko lesion classification system assesses SC hyperintensities as follows: 0 = absent, 1 = punctate, 2 = rounded \<5 mm, 3 = irregular \>5 mm, 4 = confluent lesions. Subjects were also assessed for relapse, as defined by the Montgomery-Asberg Depression Rating Scale (MADRS)and the Young Mania Rating Scale (YMRS).

Outcome measures

Outcome measures
Measure
Responders to Acute Treatment
n=9 Participants
Subjects in an acute manic episode who responded to treatment as measured by a Young Mania Rating Scale (YMRS) \<15 by week 3, which was the protocol-defined determination point for response to treatment.
Non-Responders to Acute Treatment
n=7 Participants
Subjects in an acute manic episode who did not respond to treatment as measured by a YMRS \>15 by week 3.
Boyko Subcortical (SC) Hyperintensity Value >2 in Subjects Who Received Continuation Treatment
2 participants
4 participants

SECONDARY outcome

Timeframe: up to 12 months

Population: Number of subjects in continuation phase who had MRIs that were able to be processed for DTI data.

As an exploratory analysis, subject MRI's were also evaluated using diffusion tensor imaging (DTI) for differences in fractional anisoptery (fa) in the Left Orbitofrontal area (LOFC). FA is a scalar value between zero and one hundred that describes the degree of anisotropy of a diffusion process. A value of zero means that the diffusion is isotropic (unrestricted in all directions). A value of one hundred means that diffusion occurs only along one axis and is fully restricted along all other directions.

Outcome measures

Outcome measures
Measure
Responders to Acute Treatment
n=7 Participants
Subjects in an acute manic episode who responded to treatment as measured by a Young Mania Rating Scale (YMRS) \<15 by week 3, which was the protocol-defined determination point for response to treatment.
Non-Responders to Acute Treatment
n=3 Participants
Subjects in an acute manic episode who did not respond to treatment as measured by a YMRS \>15 by week 3.
fa LOFC in Subjects Who Received Continuation Treatment
76.3 units on a scale
Standard Deviation 8.18
81.4 units on a scale
Standard Deviation 1.81

SECONDARY outcome

Timeframe: up to 12 months

Population: Number of subjects in continuation phase who had MRIs that were able to be processed for DTI data.

As an exploratory analysis, subject MRI's were also evaluated using diffusion tensor imaging (DTI) for differences in fractional anisoptery (fa) in the Right Orbitofrontal area (ROFC). FA is a scalar value between zero and one hundred that describes the degree of anisotropy of a diffusion process. A value of zero means that the diffusion is isotropic (unrestricted in all directions). A value of one hundred means that diffusion occurs only along one axis and is fully restricted along all other directions.

Outcome measures

Outcome measures
Measure
Responders to Acute Treatment
n=7 Participants
Subjects in an acute manic episode who responded to treatment as measured by a Young Mania Rating Scale (YMRS) \<15 by week 3, which was the protocol-defined determination point for response to treatment.
Non-Responders to Acute Treatment
n=4 Participants
Subjects in an acute manic episode who did not respond to treatment as measured by a YMRS \>15 by week 3.
fa ROFC in Subjects Who Received Continuation Treatment
76.1 units on a scale
Standard Deviation 6.56
79.8 units on a scale
Standard Deviation 1.39

Adverse Events

Naturalistic Treatment

Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Naturalistic Treatment
n=19 participants at risk
Patients were treated acutely using expert consensus guidelines beginning with valproic acid. After stabilization, subjects were followed monthly up to a year's duration and treated using expert consensus guidelines. indicated.
Nervous system disorders
Lithium Toxicity
5.3%
1/19 • Number of events 1

Other adverse events

Adverse event data not reported

Additional Information

John Beyer, MD

Duke University Medical Center

Phone: 919-668-0209

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place