Back to resultsComplementary Neurosteroid Intervention in Gulf War Illnesses (GWVI)
Primary Purpose
Fatigue, Musculoskeletal Pain, Cognitive Decline
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pregnenolone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Fatigue focused on measuring Pregnenolone, Gulf War Veteran, Fatigue, Musculoskeletal Pain, Cognitive Decline, Placebo Control
Eligibility Criteria
Inclusion Criteria:
- Veterans deployed to the Gulf War theatre of operations between 1990 and 1991.
- Veterans who report at least 2 of the following 3 symptoms that began in 1990 or thereafter, that lasted for more than 6 months, and that are present at the time of screening: 1) fatigue that limited usual activity, 2) musculoskeletal pain involving 2 or more regions of the body, 3) cognitive symptoms (memory, concentration, or attentional difficulties by self-report)
- Stable on medication regimen (no change in last 4 weeks) and no anticipated change in medication during study.
- Able to provide informed consent for study participation.
Exclusion Criteria:
- Subjects with a history of clinically significant neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorders (e.g. unstable angina, seizures, cerebrovascular accident, decompensated congestive heart failure, central nervous system (CNS) infection, cancer [other than non-melanoma skin cancer], or history of HIV seropositivity), which would pose a risk to the patient if s/he were to participate in the study or that might confound the results of the study.
- Concurrent enrollment in another clinical trial.
- Pregnant women or women of child-bearing potential who are not surgically-sterile or not using appropriate methods of birth control.
- Use of oral contraceptives or other hormonal supplementation such as estrogen [although early studies suggested no effects on menstrual cycle, alterations in downstream metabolites or pregnenolone (such as estradiol) could theoretically impact the efficacy or oral contraceptives and/or estrogen replacement]. Similarly, it is theoretically possible that pregnenolone could be metabolized to other steroids such a DHEA, potentially resulting in hair, skin, or other steroid-related changes. Since the investigators' have determined in their prior study that pregnenolone administration does not result in downstream elevations in DHEA, DHEAS, estradiol, or testosterone, these possibilities may be unlikely.
- Women who are breast-feeding.
- Use of narcotic interventions.
- Known allergy to study medication.
- History of moderate or severe TBI (with loss of consciousness greater than 30 minutes)
- A clearly defined disease entity that accounts for the Veteran's symptoms.
- Current DSM-IV/DSM-IVTR/DSM-V diagnosis of bipolar I disorder, schizophrenia or other psychotic disorder, or dementia.
- Subjects with a DSM-IV/DSM-IVTR/DSM-V diagnosis of alcohol or substance dependence (other than nicotine or caffeine) within the last month.
- Subjects with a current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern.
- If in the judgment of the PI it is not in the subject's best interest to participate.
- Final eligibility decisions will be determined by the PI.
Sites / Locations
- Durham VA Medical Center, Durham, NC
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Pregnenolone (Arm 1)
Placebo (Arm 2)
Arm Description
Pregnenolone
Placebo
Outcomes
Primary Outcome Measures
Physical Component of the SF-36
These data report changes in the mean scores in physical health symptoms at Week 8 Post-Randomization and Week 4 Post-Randomization, relative to Baseline. The SF-36 is a health survey with an 8-scale profile embedded in 36 questions that measures physical and mental components of health. Each item is scored on a 0 to 100 range, with the lowest and highest possible scores set at 0 and 100, respectively. All of these items are scored such that a high score defines a more favorable health state, and the Physical Component Score is an average of 4 of the 8 domains of the SF-36. Thus, positive changes in scores represent an improvement relative to baseline.
Secondary Outcome Measures
Brief Pain Inventory (BPI)
These data report changes in the mean scores in pain symptoms at Week 8 Post-Randomization and Week 4 Post-Randomization, relative to Baseline. The Brief Pain Inventory is a 14-item self-report measure designed to assess the severity, frequency and daily pattern of pain, as well as its perceived interference with quality of life. Severity is measured on a 0-10 scale with 10 being the greatest pain. Interference score is measured by a mean score of 7 items (0-10 scale) with 10 being the greatest interference. Thus, negative changes in scores represent an improvement relative to baseline.
Tower of London Test of the Brief Assessment of Cognition in Affective Disorders (BAC-A)
These data report changes in the mean scores in cognitive symptoms at Week 8 Post-Randomization and Week 4 Post-Randomization, relative to Baseline. The Tower of London test assesses executive functioning on a scale of 0-20. (Note, if a perfect score of 20 occurs then there is the opportunity of 2 additional points, increasing the score to 22.) The higher the number, the higher the degree of executive functioning. Thus, positive changes in scores represent an improvement relative to baseline.
Multidimensional Fatigue Inventory (MFI)
These data report changes in the mean scores in fatigue symptoms at Week 8 Post-Randomization and Week 4 Post-Randomization, relative to Baseline. The MFI is a 20-item self-report measure designed to assess the principal manifestations of fatigue. Items are rated on a 1-5 scale indicating how true each statement was for the respondent during the last week, with some questions scored in an inverse fashion in the final calculation of the score. The 20 items are then summed, with higher scores representing greater fatigue. Thus, negative changes in scores represent an improvement relative to baseline.
Global Severity Index of the Symptom Checklist-90-Revised (SCL-90R)
These data report changes in the mean scores in psychiatric symptoms at Week 8 Post-Randomization and Week 4 Post-Randomization, relative to Baseline. The SCL-90R is used as a screening measure of general psychiatric symptomatology. It includes dimensions measuring somatization, obsessive-compulsive, depression, anxiety, phobic anxiety, hostility, interpersonal sensitivity, paranoid ideation, and psychoticism. Global Severity Index (GSI) of the SCL-90R is designed to measure overall psychological distress. Higher scores reflect greater distress. This is a 90 item measure with each rated on a scale of 0-4, with 4 being the highest level of psychological distress for each item. Thus, negative changes in scores represent an improvement relative to baseline.
Full Information
NCT ID
NCT01956279
First Posted
September 11, 2013
Last Updated
April 30, 2020
Sponsor
VA Office of Research and Development
1. Study Identification
Unique Protocol Identification Number
NCT01956279
Brief Title
Complementary Neurosteroid Intervention in Gulf War Illnesses (GWVI)
Official Title
Complementary Neurosteroid Intervention in Gulf War Illnesses (GWVI)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
October 1, 2013 (Actual)
Primary Completion Date
October 10, 2018 (Actual)
Study Completion Date
October 10, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will investigate the use of adjunctive pregnenolone for the following:
fatigue that has limited usual activity,
musculoskeletal pain involving 2 or more regions of the body and,
cognitive symptoms (memory, concentration, or attentional difficulties by self-report) in Veterans deployed to the Gulf War theatre of operations between 1990 and 1991.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fatigue, Musculoskeletal Pain, Cognitive Decline
Keywords
Pregnenolone, Gulf War Veteran, Fatigue, Musculoskeletal Pain, Cognitive Decline, Placebo Control
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
170 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pregnenolone (Arm 1)
Arm Type
Experimental
Arm Description
Pregnenolone
Arm Title
Placebo (Arm 2)
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Pregnenolone
Intervention Description
Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x 28 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo 50mg BID x 14 days, followed by Placebo 150 x 14 days, followed by Placebo 250 mg BID x 28 days
Primary Outcome Measure Information:
Title
Physical Component of the SF-36
Description
These data report changes in the mean scores in physical health symptoms at Week 8 Post-Randomization and Week 4 Post-Randomization, relative to Baseline. The SF-36 is a health survey with an 8-scale profile embedded in 36 questions that measures physical and mental components of health. Each item is scored on a 0 to 100 range, with the lowest and highest possible scores set at 0 and 100, respectively. All of these items are scored such that a high score defines a more favorable health state, and the Physical Component Score is an average of 4 of the 8 domains of the SF-36. Thus, positive changes in scores represent an improvement relative to baseline.
Time Frame
Baseline to week 4, and Baseline to week 8
Secondary Outcome Measure Information:
Title
Brief Pain Inventory (BPI)
Description
These data report changes in the mean scores in pain symptoms at Week 8 Post-Randomization and Week 4 Post-Randomization, relative to Baseline. The Brief Pain Inventory is a 14-item self-report measure designed to assess the severity, frequency and daily pattern of pain, as well as its perceived interference with quality of life. Severity is measured on a 0-10 scale with 10 being the greatest pain. Interference score is measured by a mean score of 7 items (0-10 scale) with 10 being the greatest interference. Thus, negative changes in scores represent an improvement relative to baseline.
Time Frame
Baseline to week 4, and Baseline to week 8
Title
Tower of London Test of the Brief Assessment of Cognition in Affective Disorders (BAC-A)
Description
These data report changes in the mean scores in cognitive symptoms at Week 8 Post-Randomization and Week 4 Post-Randomization, relative to Baseline. The Tower of London test assesses executive functioning on a scale of 0-20. (Note, if a perfect score of 20 occurs then there is the opportunity of 2 additional points, increasing the score to 22.) The higher the number, the higher the degree of executive functioning. Thus, positive changes in scores represent an improvement relative to baseline.
Time Frame
Baseline to week 4, and Baseline to week 8
Title
Multidimensional Fatigue Inventory (MFI)
Description
These data report changes in the mean scores in fatigue symptoms at Week 8 Post-Randomization and Week 4 Post-Randomization, relative to Baseline. The MFI is a 20-item self-report measure designed to assess the principal manifestations of fatigue. Items are rated on a 1-5 scale indicating how true each statement was for the respondent during the last week, with some questions scored in an inverse fashion in the final calculation of the score. The 20 items are then summed, with higher scores representing greater fatigue. Thus, negative changes in scores represent an improvement relative to baseline.
Time Frame
Baseline to week 4, and Baseline to week 8
Title
Global Severity Index of the Symptom Checklist-90-Revised (SCL-90R)
Description
These data report changes in the mean scores in psychiatric symptoms at Week 8 Post-Randomization and Week 4 Post-Randomization, relative to Baseline. The SCL-90R is used as a screening measure of general psychiatric symptomatology. It includes dimensions measuring somatization, obsessive-compulsive, depression, anxiety, phobic anxiety, hostility, interpersonal sensitivity, paranoid ideation, and psychoticism. Global Severity Index (GSI) of the SCL-90R is designed to measure overall psychological distress. Higher scores reflect greater distress. This is a 90 item measure with each rated on a scale of 0-4, with 4 being the highest level of psychological distress for each item. Thus, negative changes in scores represent an improvement relative to baseline.
Time Frame
Baseline to week 4, and Baseline to week 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Veterans deployed to the Gulf War theatre of operations between 1990 and 1991.
Veterans who report at least 2 of the following 3 symptoms that began in 1990 or thereafter, that lasted for more than 6 months, and that are present at the time of screening: 1) fatigue that limited usual activity, 2) musculoskeletal pain involving 2 or more regions of the body, 3) cognitive symptoms (memory, concentration, or attentional difficulties by self-report)
Stable on medication regimen (no change in last 4 weeks) and no anticipated change in medication during study.
Able to provide informed consent for study participation.
Exclusion Criteria:
Subjects with a history of clinically significant neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorders (e.g. unstable angina, seizures, cerebrovascular accident, decompensated congestive heart failure, central nervous system (CNS) infection, cancer [other than non-melanoma skin cancer], or history of HIV seropositivity), which would pose a risk to the patient if s/he were to participate in the study or that might confound the results of the study.
Concurrent enrollment in another clinical trial.
Pregnant women or women of child-bearing potential who are not surgically-sterile or not using appropriate methods of birth control.
Use of oral contraceptives or other hormonal supplementation such as estrogen [although early studies suggested no effects on menstrual cycle, alterations in downstream metabolites or pregnenolone (such as estradiol) could theoretically impact the efficacy or oral contraceptives and/or estrogen replacement]. Similarly, it is theoretically possible that pregnenolone could be metabolized to other steroids such a DHEA, potentially resulting in hair, skin, or other steroid-related changes. Since the investigators' have determined in their prior study that pregnenolone administration does not result in downstream elevations in DHEA, DHEAS, estradiol, or testosterone, these possibilities may be unlikely.
Women who are breast-feeding.
Use of narcotic interventions.
Known allergy to study medication.
History of moderate or severe TBI (with loss of consciousness greater than 30 minutes)
A clearly defined disease entity that accounts for the Veteran's symptoms.
Current DSM-IV/DSM-IVTR/DSM-V diagnosis of bipolar I disorder, schizophrenia or other psychotic disorder, or dementia.
Subjects with a DSM-IV/DSM-IVTR/DSM-V diagnosis of alcohol or substance dependence (other than nicotine or caffeine) within the last month.
Subjects with a current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern.
If in the judgment of the PI it is not in the subject's best interest to participate.
Final eligibility decisions will be determined by the PI.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christine E. Marx, MD MA
Organizational Affiliation
Durham VA Medical Center, Durham, NC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Durham VA Medical Center, Durham, NC
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Complementary Neurosteroid Intervention in Gulf War Illnesses (GWVI)
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