Gulf War Illness
Conditions
Keywords
Veterans, neuropsychology, fatigue, Chronic Multisymptom Illness, Gulf War Illness, behavioral treatment
Brief summary
There are almost 700,000 Gulf War Veterans (GWV) with 25-30% suffering from a devastating multi-symptom illness coined Gulf War Illness (GWI). GWV with GWI report significant activity limitations and chronic cognitive problems consistent with problem-solving deficits. Problem-solving is considered the most complex of cognitive abilities and is what enables us to conduct complicated behaviors such as setting goals, sequencing and multi-tasking. As a result studies have found that problem-solving deficits are prospectively related to a greater risk of disability. Despite published reports documenting these problems there are no treatments that target the problem-solving deficits of GWI. This proposal seeks to determine whether Problem-Solving Therapy, a patient centered cognitive rehabilitation therapy, can reduce disability by compensating for problem-solving deficits.
Detailed description
Gulf War Illness (GWI) is a complex multi-dimensional illness which causes as much disability as other major medical diseases. Previous clinical trials (i.e. cognitive behavioral therapy and graded exercise) for GWI have sought to improve disability by increasing activity regardless of symptom presentation. These previous trials for GWI have shown limited efficacy and poor adherence. An innovative treatment approach is to target a specific component of GWI, namely problem-solving ability, known to be associated with disability. Impairment in problem-solving ability affects Gulf War Veterans (GWV) with GWI and is prospectively related to greater risk of disability. This impairment is also related to poorer adherence to medical regimes, making it difficult for GWV to manage other aspects of GWI. Problem-solving is considered one of the most complex of cognitive abilities and is related to complicated behaviors such as setting goals, sequencing and multi-tasking. Despite published reports documenting these deficits there are no treatments that target the problem-solving deficits of GWI in order to reduce disability. The investigators propose a targeted treatment, Problem-Solving Therapy, to compensate for the problem-solving deficits of GWI and thereby reducing disability. Problem-Solving Therapy, a top down approach, teaches patients skills to overcome problems like cognitive dysfunction or physical symptoms that impact problem-solving. Compensating for problem-solving deficits would reduce disability and provide information on the effect of treating one component of GWI on other symptoms of GWI. This is the first trial of cognitive rehabilitation therapy for GWI.
Interventions
BEHAVIORALProblem-Solving Therapy
Problem-Solving Therapy is a treatment approach that teaches patients strategies to address real-life problems.
BEHAVIORALHealth Education
Health Education provides didactic information about Gulf War Illness
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Inclusion: * deployed to first Gulf War and meets Kansas definition for GWI (see definition in measures section); * scores at least a half a standard deviation worse than the mean on the World Health Organization Disability Schedule (WHO-DAS II).
Exclusion criteria
Exclusion: * current suicidal/homicide intent or plan assessed by The Columbia Suicide Severity Rating Scale, schizophrenia or current psychotic symptoms * self-reported diagnosis of a degenerative brain disorder or serious psychiatric or medical illness which may limit generalizability of the findings, limit safety or account for the symptoms of GWI. Exclusionary medical illnesses include: Class 3 and 4 heart failure, cancer diagnosed within the past year and/or undergoing active treatment (chemotherapy or radiation therapy), chronic renal insufficiency, hospitalization due to myocardial infarct, stroke in the past year, a neurodegenerative disorder, or another medical or psychiatric disorder that may limit generalizability, limit participants safety or account for the symptoms of GWI at the discretion of the PI. * a disability that would preclude telephone use.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disability - WHO-DAS 2 Change | Baseline and 12 weeks | World Health Organization Disability Assessment Schedule. The WHO-DAS 2.0 measures disability due to physical and mental health conditions. The WHO-DAS 2.0 is a 36 item measure that focuses upon six life tasks: * Understanding and communicating * Self-care * Mobility (getting around) * Interpersonal relationships (getting along with others) * Work and household roles (life activities) * Community and civic roles (participation) These six life tasks reflect two underlying constructs: Activity limitations and Participation deficits. Scores range from 0-100 with higher scores = more disability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Problem-Solving Inventory Change | Baseline and 12 weeks | Self-report problem-solving ability. Scores range from 32-192 with lower scores equally better problem-solving ability. |
| Problem-Solving Ability Change | Baseline and 12 weeks | Neuropsychological Battery includes: Halstead Category Test, Russell Revised Version, The Conner's Continuous Performance Test-3 (CPT-3), Stroop Color and Word Test, Trails Making Test A and B (TMT). Problem-solving ability was be created by standardizing (i.e., converting to z-scores) these neuropsychological tests based on administrative norms and averaging them. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched). Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population and higher scores reflecting greater problem solving. |
| Disability - WHO-DAS 2 Change | Baseline and 6 months | World Health Organization Disability Assessment Schedule. The WHO-DAS 2.0 measures disability due to physical and mental health conditions. The WHO-DAS 2.0 is a 36 item measure that focuses upon six life tasks: * Understanding and communicating * Self-care * Mobility (getting around) * Interpersonal relationships (getting along with others) * Work and household roles (life activities) * Community and civic roles (participation) These six life tasks reflect two underlying constructs: Activity limitations and Participation deficits. Scores range from 0-100 with higher scores = more disability. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Multidimensional Pain Inventory - Pain Severity Subscale Change | baseline and 12 weeks | three items assessing pain severity. scores range 0-18 with higher scores=worse severity |
| Fatigue Change | Baseline and 12 weeks | The Fatigue Severity Scale (FSS). Scale from 9 to 63 with higher scores = worse fatigue |
| Pain Disability Change | Baseline and 12 weeks | Pain Disability Index (PDI). Scale ranges from 0-70 with higher scores meaning worse disability. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Problem-Solving Therapy Problem-Solving Therapy is a treatment approach that teaches patients strategies to address real-life problems.
Problem-Solving Therapy: Problem-Solving Therapy is a treatment approach that teaches patients strategies to address real-life problems. | 135 |
| Health Education Health education provides didactic information about Gulf War Illness
Health Education: Health Education provides didactic information about Gulf War Illness | 133 |
| Total | 268 |
Baseline characteristics
| Characteristic | Problem-Solving Therapy | Total | Health Education |
|---|---|---|---|
| Age, Continuous | 53.1 years STANDARD_DEVIATION 7.6 | 52.9 years STANDARD_DEVIATION 7.3 | 52.8 years STANDARD_DEVIATION 7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 18 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 118 Participants | 233 Participants | 115 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 17 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants | 12 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 30 Participants | 63 Participants | 33 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 91 Participants | 179 Participants | 88 Participants |
| Region of Enrollment United States | 135 Participants | 268 Participants | 133 Participants |
| Sex: Female, Male Female | 15 Participants | 31 Participants | 16 Participants |
| Sex: Female, Male Male | 120 Participants | 237 Participants | 117 Participants |
| World Health Organization DIsability Assessment Schedule 2.0 | 46 units on a scale STANDARD_DEVIATION 18.1 | 45.4 units on a scale STANDARD_DEVIATION 18.6 | 44.8 units on a scale STANDARD_DEVIATION 19.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 135 | 0 / 133 |
| other Total, other adverse events | 15 / 135 | 14 / 133 |
| serious Total, serious adverse events | 21 / 135 | 31 / 133 |
Outcome results
Primary
Disability - WHO-DAS 2 Change
World Health Organization Disability Assessment Schedule. The WHO-DAS 2.0 measures disability due to physical and mental health conditions. The WHO-DAS 2.0 is a 36 item measure that focuses upon six life tasks: * Understanding and communicating * Self-care * Mobility (getting around) * Interpersonal relationships (getting along with others) * Work and household roles (life activities) * Community and civic roles (participation) These six life tasks reflect two underlying constructs: Activity limitations and Participation deficits. Scores range from 0-100 with higher scores = more disability.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Problem-Solving Therapy | Disability - WHO-DAS 2 Change | -2.81 score on a scale | Standard Error 1.16 |
| Health Education | Disability - WHO-DAS 2 Change | -2.21 score on a scale | Standard Error 1.12 |
p-value: 0.712Mixed Models Analysis
Secondary
Disability - WHO-DAS 2 Change
World Health Organization Disability Assessment Schedule. The WHO-DAS 2.0 measures disability due to physical and mental health conditions. The WHO-DAS 2.0 is a 36 item measure that focuses upon six life tasks: * Understanding and communicating * Self-care * Mobility (getting around) * Interpersonal relationships (getting along with others) * Work and household roles (life activities) * Community and civic roles (participation) These six life tasks reflect two underlying constructs: Activity limitations and Participation deficits. Scores range from 0-100 with higher scores = more disability.
Time frame: Baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Problem-Solving Therapy | Disability - WHO-DAS 2 Change | -2.61 score on a scale | Standard Error 1.45 |
| Health Education | Disability - WHO-DAS 2 Change | 1.11 score on a scale | Standard Error 1.29 |
p-value: 0.057Mixed Models Analysis
Secondary
Problem-Solving Ability Change
Neuropsychological Battery includes: Halstead Category Test, Russell Revised Version, The Conner's Continuous Performance Test-3 (CPT-3), Stroop Color and Word Test, Trails Making Test A and B (TMT). Problem-solving ability was be created by standardizing (i.e., converting to z-scores) these neuropsychological tests based on administrative norms and averaging them. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched). Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population and higher scores reflecting greater problem solving.
Time frame: Baseline and 12 weeks
Population: Participants who were unable to come in person did not complete this measure, as a result the overall number analyzed was smaller.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Problem-Solving Therapy | Problem-Solving Ability Change | 13.81 score on a scale | Standard Error 7.5 |
| Health Education | Problem-Solving Ability Change | 1.58 score on a scale | Standard Error 7.29 |
p-value: 0.244Mixed Models Analysis
Secondary
Problem-Solving Inventory Change
Self-report problem-solving ability. Scores range from 32-192 with lower scores equally better problem-solving ability.
Time frame: Baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Problem-Solving Therapy | Problem-Solving Inventory Change | -7.03 score on a scale | Standard Error 2.91 |
| Health Education | Problem-Solving Inventory Change | 0.26 score on a scale | Standard Error 1.94 |
p-value: 0.013Mixed Models Analysis
Secondary
Problem-Solving Inventory Change
Self-report problem-solving ability. Scores range from 32-192 with lower scores equally better problem-solving ability.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Problem-Solving Therapy | Problem-Solving Inventory Change | -12.77 score on a scale | Standard Error 1.77 |
| Health Education | Problem-Solving Inventory Change | -6.53 score on a scale | Standard Error 1.74 |
p-value: 0.013Mixed Models Analysis
Other Pre-specified
Fatigue Change
The Fatigue Severity Scale (FSS). Scale from 9 to 63 with higher scores = worse fatigue
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Problem-Solving Therapy | Fatigue Change | -2.71 score on a scale | Standard Error 0.98 |
| Health Education | Fatigue Change | -0.82 score on a scale | Standard Error 0.95 |
p-value: 0.168Mixed Models Analysis
Other Pre-specified
Multidimensional Pain Inventory - Pain Severity Subscale Change
three items assessing pain severity. scores range 0-18 with higher scores=worse severity
Time frame: baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Problem-Solving Therapy | Multidimensional Pain Inventory - Pain Severity Subscale Change | 0 score on a scale | Standard Error 0.1 |
| Health Education | Multidimensional Pain Inventory - Pain Severity Subscale Change | -0.06 score on a scale | Standard Error 0.1 |
p-value: 0.703Mixed Models Analysis
Other Pre-specified
Pain Disability Change
Pain Disability Index (PDI). Scale ranges from 0-70 with higher scores meaning worse disability.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Problem-Solving Therapy | Pain Disability Change | -2.05 score on a scale | Standard Error 1.13 |
| Health Education | Pain Disability Change | -0.68 score on a scale | Standard Error 1.09 |
p-value: 0.382Mixed Models Analysis