Bipolar Disorder
Conditions
Keywords
BPD
Brief summary
The purpose of this study is to look at certain structural changes in the brain in people with bipolar disorder or those with a history of Bipolar disorder.
Detailed description
Individuals with bipolar disorder or those with a history of bipolar disorder may have certain structural changes in their brain. The purpose of this study is to look at those changes, as well as the assessment of risk factors for bipolar disorders, involving both social and psychological aspects of behavior, age, education, marital relations, nutrition, physical activity, etc., compared with persons not having bipolar disorder. These changes in the brain will be measured by Magnetic Resonance Imaging (MRI).
Interventions
DRUGValproic Acid
Tablets, 250mg-3000mg
Sponsors
Duke University
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
1. DSM-IV diagnosis of bipolar Disorder, Manic and mixed episodes. 2. 18 years of age and older, male or female, any race. 3. Capacity to give informed consent and follow study procedures.
Exclusion criteria
1. History of alcohol/drug dependence 2. Any metal or pacemaker in the body which precludes MRI 3. Pregnancy 4. Dementia or other primary psychiatric disorders including substance abuse/dependence, anxiety disorders, schizophrenia 5. For controls, numbers one through four above as well as any history of depression or the use of antidepressants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Boyko DWM Hyperintensity Value >2 in Subjects Who Received Acute Treatment for Mania | 3 weeks | 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. |
| Boyko DWM Hyperintensity Value >2 in Subjects Who Received Continuation Treatment | 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Boyko Subcortical (SC) Hyperintensity Value >2 in Subjects Who Received Continuation Treatment | up to 12 months | 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). |
| fa LOFC in Subjects Who Received Continuation Treatment | up to 12 months | 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. |
| fa ROFC in Subjects Who Received Continuation Treatment | up to 12 months | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
Only subjects currently in a manic episode were recruited for the acute treatment protocol substudy.
Participants by arm
| Arm | Count |
|---|---|
| Naturalistic Treatment | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Continuation Treatment -- up to 12 Month | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Naturalistic Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 49.68 years STANDARD_DEVIATION 17.84 |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 19 |
| serious Total, serious adverse events | 1 / 19 |
Outcome results
Primary
Boyko DWM Hyperintensity Value >2 in Subjects Who Received Acute Treatment for Mania
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.
Time frame: 3 weeks
Population: All subjects in an acute manic state who were treated with specified protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Responders to Acute Treatment | Boyko DWM Hyperintensity Value >2 in Subjects Who Received Acute Treatment for Mania | 10 participants |
| Non-Responders to Acute Treatment | Boyko DWM Hyperintensity Value >2 in Subjects Who Received Acute Treatment for Mania | 9 participants |
p-value: >0.05Chi-squared
Primary
Boyko DWM Hyperintensity Value >2 in Subjects Who Received 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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Responders to Acute Treatment | Boyko DWM Hyperintensity Value >2 in Subjects Who Received Continuation Treatment | 4 participants |
| Non-Responders to Acute Treatment | Boyko DWM Hyperintensity Value >2 in Subjects Who Received Continuation Treatment | 4 participants |
p-value: 1Chi-squared
Secondary
Boyko Subcortical (SC) Hyperintensity Value >2 in Subjects Who Received Continuation Treatment
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).
Time frame: up to 12 months
Population: Number of subjects who who had \>2 on the DWM hyperintensity assessment from the Boyko classification system.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Responders to Acute Treatment | Boyko Subcortical (SC) Hyperintensity Value >2 in Subjects Who Received Continuation Treatment | 2 participants |
| Non-Responders to Acute Treatment | Boyko Subcortical (SC) Hyperintensity Value >2 in Subjects Who Received Continuation Treatment | 4 participants |
p-value: 0.6056Chi-squared
Secondary
fa LOFC in Subjects Who Received Continuation Treatment
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.
Time frame: up to 12 months
Population: Number of subjects in continuation phase who had MRIs that were able to be processed for DTI data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Responders to Acute Treatment | fa LOFC in Subjects Who Received Continuation Treatment | 76.3 units on a scale | Standard Deviation 8.18 |
| Non-Responders to Acute Treatment | fa LOFC in Subjects Who Received Continuation Treatment | 81.4 units on a scale | Standard Deviation 1.81 |
p-value: 0.081t-test, 1 sided
Secondary
fa ROFC in Subjects Who Received Continuation Treatment
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.
Time frame: up to 12 months
Population: Number of subjects in continuation phase who had MRIs that were able to be processed for DTI data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Responders to Acute Treatment | fa ROFC in Subjects Who Received Continuation Treatment | 76.1 units on a scale | Standard Deviation 6.56 |
| Non-Responders to Acute Treatment | fa ROFC in Subjects Who Received Continuation Treatment | 79.8 units on a scale | Standard Deviation 1.39 |
p-value: 0.091t-test, 1 sided