CompletedNCT01956279Updated May 1, 2020Results posted

Complementary Neurosteroid Intervention in Gulf War Illnesses (GWVI)

A Phase 2 interventional study of Pregnenolone and Placebo in Fatigue, Musculoskeletal Pain and Cognitive Decline, sponsored by VA Office of Research and Development. Completed at 1 site in United States. Open to participants aged 40 Years to 65 Years. Per ClinicalTrials.gov, last updated 2020-05-01.

Sponsored by VA Office of Research and Development · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 170
Allocation: Randomized
Ages: 40 Years to 65 Years
Sex: All

Study 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.

Conditions studied

Fatigue
Musculoskeletal Pain
Cognitive Decline

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Keywords

Pregnenolone
Gulf War Veteran
Fatigue
Musculoskeletal Pain
Cognitive Decline
Placebo Control

In context

Musculoskeletal Pain

493 studies on the registry are indexed under Musculoskeletal Pain; 113 are open to participants now.

This study's enrollment of 170 is above the median of 69 across 346 interventional studies indexed under Musculoskeletal Pain.

Browse Musculoskeletal Pain studies →

Lead sponsor

VA Office of Research and Development is the lead sponsor of 1,733 studies on the registry; 396 are open to participants now.

Of its 206 completed or terminated interventional studies of FDA-regulated products, 180 (87%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 40 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 170 participants (actual)

Study arms

Experimental
Pregnenolone (Arm 1)
Pregnenolone
Drug: Pregnenolone
Placebo comparator
Placebo (Arm 2)
Placebo
Drug: Placebo

Interventions

DrugPregnenolone
Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x 28 days
DrugPlacebo
Placebo 50mg BID x 14 days, followed by Placebo 150 x 14 days, followed by Placebo 250 mg BID x 28 days

What researchers measure

Primary outcomes

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.
Time frame: Baseline to week 4, and Baseline to week 8

Secondary outcomes

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.
Time frame: Baseline to week 4, and Baseline to week 8
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.
Time frame: Baseline to week 4, and Baseline to week 8
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.
Time frame: Baseline to week 4, and Baseline to week 8
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.
Time frame: Baseline to week 4, and Baseline to week 8

Results

Posted May 1, 2020

Participant flow

Participant flow — Overall Study
Milestone	Pregnenolone (Arm 1)	Placebo (Arm 2)
Started	82	88
Completed	68	74
Not completed	14	14

Outcome measures

PrimaryPhysical 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.

Time frame:: Baseline to week 4, and Baseline to week 8
Reported as:: Mean · score on a scale

Physical Component of the SF-36
score on a scale	Pregnenolone (Arm 1)	Placebo (Arm 2)
Baseline to week 4	2.04 ± 1.50	2.55 ± 1.55
Baseline to week 8	1.23 ± 1.68	4.45 ± 1.75

SecondaryBrief 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.

Time frame:: Baseline to week 4, and Baseline to week 8
Reported as:: Mean · score on a scale

Brief Pain Inventory (BPI)
score on a scale	Pregnenolone (Arm 1)	Placebo (Arm 2)
Pain rating, Baseline to week 4	-0.44 ± 0.14	-0.30 ± 0.15
Pain rating, Baseline to week 8	-0.09 ± 0.21	-0.11 ± 0.22
Interference, Baseline to week 4	-0.03 ± 0.22	0.00 ± 0.21
Interference, Baseline to week 8	-0.19 ± 0.25	-0.26 ± 0.29

SecondaryTower 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.

Time frame:: Baseline to week 4, and Baseline to week 8
Reported as:: Mean · score on a scale

Tower of London Test of the Brief Assessment of Cognition in Affective Disorders (BAC-A)
score on a scale	Pregnenolone (Arm 1)	Placebo (Arm 2)
Baseline to week 4	1.15 ± 0.37	1.31 ± 0.39
Baseline to week 8	0.98 ± 0.37	1.71 ± 0.41

SecondaryMultidimensional 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.

Time frame:: Baseline to week 4, and Baseline to week 8
Reported as:: Mean · score on a scale

Multidimensional Fatigue Inventory (MFI)
score on a scale	Pregnenolone (Arm 1)	Placebo (Arm 2)
Baseline to week 4	-0.76 ± 1.24	-0.27 ± 1.04
Baseline to week 8	-3.63 ± 1.45	-3.22 ± 1.18

SecondaryGlobal 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.

Time frame:: Baseline to week 4, and Baseline to week 8
Reported as:: Mean · score on a scale

Global Severity Index of the Symptom Checklist-90-Revised (SCL-90R)
score on a scale	Pregnenolone (Arm 1)	Placebo (Arm 2)
Baseline to week 4	-0.12 ± 0.04	-0.09 ± 0.04
Baseline to week 8	-0.16 ± 0.05	-0.15 ± 0.05

Adverse events

Collected over Participants were followed for 10 weeks (or somewhat less if the participant was lost to follow-up or withdrawn during the study), with all subjects completed in a 4.5 year span.. Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Pregnenolone (Arm 1)	1/82 (1.2%)	1/82 (1.2%)	69/82 (84.1%)
Placebo (Arm 2)	0/88 (0%)	0/88 (0%)	73/88 (83%)

Most frequent serious events

Most frequent serious events
Event	Pregnenolone (Arm 1)	Placebo (Arm 2)
Participant death by homicideGeneral disorders	1/82	0/88

Most frequent other events

Showing 10 of 56

Most frequent other events
Event	Pregnenolone (Arm 1)	Placebo (Arm 2)
Nasal CongestionGeneral disorders	20/82	33/88
HeadacheNervous system disorders	28/82	25/88
DiarrheaGastrointestinal disorders	24/82	26/88
Dry MouthNervous system disorders	15/82	22/88
CrampsMusculoskeletal and connective tissue disorders	18/82	21/88
DrowsinessNervous system disorders	16/82	21/88
NauseaGastrointestinal disorders	15/82	20/88
Blurred VisionEye disorders	10/82	19/88
DermatologicalSkin and subcutaneous tissue disorders	17/82	19/88
DizzinessNervous system disorders	17/82	17/88

Baseline characteristics

28 of the 170 participants were withdrawn from the study prior to reaching week 4 post-randomization.

Age, Categorical
Age, Categorical(Participants)	Pregnenolone (Arm 1)	Placebo (Arm 2)	Total
<=18 years	0	0	0
Between 18 and 65 years	81	88	169
>=65 years	1	0	1

Age, Continuous
Age, Continuous(years)	Pregnenolone (Arm 1)	Placebo (Arm 2)	Total
Mean	52.7 ± 5.6	51.4 ± 4.8	52.0 ± 5.2

Sex: Female, Male
Sex: Female, Male(Participants)	Pregnenolone (Arm 1)	Placebo (Arm 2)	Total
Female	10	10	20
Male	72	78	150

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Pregnenolone (Arm 1)	Placebo (Arm 2)	Total
Hispanic or Latino	6	1	7
Not Hispanic or Latino	76	87	163
Unknown or Not Reported	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Pregnenolone (Arm 1)	Placebo (Arm 2)	Total
American Indian or Alaska Native	0	2	2
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	40	56	96
White	42	30	72
More than one race	0	0	0
Unknown or Not Reported	0	0	0

Region of Enrollment
Region of Enrollment(Participants)	Pregnenolone (Arm 1)	Placebo (Arm 2)	Total
United States	82	88	170

Study locations

1 site

Durham VA Medical Center, Durham, NC
Durham, North Carolina 27705, United States

References and documents

Study documents

Protocol and statistical analysis plan · Feb 20, 2015

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 1, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01956279
Lead sponsor: VA Office of Research and Development
Responsible party: Sponsor
First posted: Oct 8, 2013
Start date: Oct 1, 2013
Primary completion: Oct 10, 2018
Completion: Oct 10, 2018
Results posted: May 1, 2020
Last update: May 1, 2020

Study contacts

Christine E. Marx, MD MA

principal investigator · Durham VA Medical Center, Durham, NC

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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