NCT01956279

Complementary Neurosteroid Intervention in Gulf War Illnesses (GWVI)

Completed Phase 2 Results posted Last updated 1 May 2020

What this trial tests

Phase 2 trial testing Pregnenolone in Fatigue in 170 participants. Completed in 10 October 2018.

Timeline

1 October 2013

Primary endpoint
10 October 2018

10 October 2018

Quick facts

Lead sponsor	VA Office of Research and Development
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	170
Start date	1 October 2013
Primary completion	10 October 2018
Estimated completion	10 October 2018
Sites	1 location across United States

Drugs / interventions tested

• Pregnenolone — full drug profile →
• Placebo

Conditions studied

• Fatigue — all drugs for Fatigue →
• Musculoskeletal Pain — all drugs for Musculoskeletal Pain →
• Cognitive Decline — all drugs for Cognitive Decline →

Sponsor

VA Office of Research and Development — full company profile →

Who can join

Adults 40 to 65, any sex, with Fatigue or Musculoskeletal Pain. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Physical Component of the SF-36 Primary · Baseline to week 4, and Baseline to week 8

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 chan

Baseline to week 4

Group	Value	95% CI
Pregnenolone (Arm 1)	2.04	± 1.50
Placebo (Arm 2)	2.55	± 1.55

Baseline to week 8

Group	Value	95% CI
Pregnenolone (Arm 1)	1.23	± 1.68
Placebo (Arm 2)	4.45	± 1.75

Brief Pain Inventory (BPI) Secondary · Baseline to week 4, and Baseline to week 8

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.

Pain rating, Baseline to week 4

Group	Value	95% CI
Pregnenolone (Arm 1)	-0.44	± 0.14
Placebo (Arm 2)	-0.30	± 0.15

Pain rating, Baseline to week 8

Group	Value	95% CI
Pregnenolone (Arm 1)	-0.09	± 0.21
Placebo (Arm 2)	-0.11	± 0.22

Interference, Baseline to week 4

Group	Value	95% CI
Pregnenolone (Arm 1)	-0.03	± 0.22
Placebo (Arm 2)	0.00	± 0.21

Interference, Baseline to week 8

Group	Value	95% CI
Pregnenolone (Arm 1)	-0.19	± 0.25
Placebo (Arm 2)	-0.26	± 0.29

Tower of London Test of the Brief Assessment of Cognition in Affective Disorders (BAC-A) Secondary · Baseline to week 4, and Baseline to week 8

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.

Baseline to week 4

Group	Value	95% CI
Pregnenolone (Arm 1)	1.15	± 0.37
Placebo (Arm 2)	1.31	± 0.39

Baseline to week 8

Group	Value	95% CI
Pregnenolone (Arm 1)	0.98	± 0.37
Placebo (Arm 2)	1.71	± 0.41

Multidimensional Fatigue Inventory (MFI) Secondary · Baseline to week 4, and Baseline to week 8

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 base

Baseline to week 4

Group	Value	95% CI
Pregnenolone (Arm 1)	-0.76	± 1.24
Placebo (Arm 2)	-0.27	± 1.04

Baseline to week 8

Group	Value	95% CI
Pregnenolone (Arm 1)	-3.63	± 1.45
Placebo (Arm 2)	-3.22	± 1.18

Global Severity Index of the Symptom Checklist-90-Revised (SCL-90R) Secondary · Baseline to week 4, and Baseline to week 8

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 s

Baseline to week 4

Group	Value	95% CI
Pregnenolone (Arm 1)	-0.12	± 0.04
Placebo (Arm 2)	-0.09	± 0.04

Baseline to week 8

Group	Value	95% CI
Pregnenolone (Arm 1)	-0.16	± 0.05
Placebo (Arm 2)	-0.15	± 0.05

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pregnenolone (Arm 1)

Serious: 1/82 (1%)

Deaths: 1/82

Placebo (Arm 2)

Serious: 0/88 (0%)

Deaths: 0/88

Serious adverse events (1 terms)

Reaction	System	Pregnenolone (Arm 1)	Placebo (Arm 2)
Participant death by homicide	General disorders	—	—

Other adverse events (56 terms — click to expand)

Reaction	System	Pregnenolone (Arm 1)	Placebo (Arm 2)
Nasal Congestion	General disorders	—	—
Headache	Nervous system disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Dry Mouth	Nervous system disorders	—	—
Cramps	Musculoskeletal and connective tissue disorders	—	—
Drowsiness	Nervous system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Blurred Vision	Eye disorders	—	—
Dermatological	Skin and subcutaneous tissue disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Dizziness	Nervous system disorders	—	—
Insomnia	Nervous system disorders	—	—
Tinnitus	Ear and labyrinth disorders	—	—
Paresthesia	Nervous system disorders	—	—
Restlessness	General disorders	—	—
Decreased Appetite	Nervous system disorders	—	—
Irritability	General disorders	—	—
Sweating	Nervous system disorders	—	—
Cold Extremities	Blood and lymphatic system disorders	—	—
Increased Appetite	Nervous system disorders	—	—
Muscle Pain/Stiffness	Musculoskeletal and connective tissue disorders	—	—
Joint Pain/Stiffness	Musculoskeletal and connective tissue disorders	—	—
Impaired Sexual Performance	Nervous system disorders	—	—
Palpitations	Cardiac disorders	—	—
Peripheral Edema	General disorders	—	—
Decreased Interest in Sex	Nervous system disorders	—	—
Pain / Stiffness	Musculoskeletal and connective tissue disorders	—	—
Myoclonus	Musculoskeletal and connective tissue disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Malaise	General disorders	—	—
Excitement / Agitation	Nervous system disorders	—	—
Akathisia	Musculoskeletal and connective tissue disorders	—	—
Increased Salivation	Nervous system disorders	—	—
Vertigo	Nervous system disorders	—	—
Fever	General disorders	—	—
Menstrual Disturbance	Reproductive system and breast disorders	—	—
Disorientation	Nervous system disorders	—	—
Rigidity	Musculoskeletal and connective tissue disorders	—	—
Tachycardia	Cardiac disorders	—	—
Tremor	Nervous system disorders	—	—

Most-reported serious reactions: Participant death by homicide.

Data from ClinicalTrials.gov NCT01956279 adverse events section.

Sponsor's own description

This study will investigate the use of adjunctive pregnenolone for the following:

1. fatigue that has limited usual activity,
2. musculoskeletal pain involving 2 or more regions of the body and,
3. cognitive symptoms (memory, concentration, or attentional difficulties by self-report) in Veterans deployed to the Gulf War theatre of operations between 1990 and 1991.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Gulf War Illness: Mechanisms Underlying Brain Dysfunction and Promising Therapeutic Strategies.
   Dickey B, Madhu LN, Shetty AK. · · 2021 · cited 54× · PMID 33164782 · DOI 10.1016/j.pharmthera.2020.107716