Complementary Neurosteroid Intervention in Gulf War Illnesses (GWVI)

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.

Study Overview

• Status: Completed
• Conditions: Fatigue; Musculoskeletal Pain; Cognitive Decline
• Intervention / Treatment: Drug: Pregnenolone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pregnenolone (Arm 1); Pregnenolone	Drug: Pregnenolone; Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x 28 days
Placebo Comparator: Placebo (Arm 2); Placebo	Drug: Placebo; Placebo 50mg BID x 14 days, followed by Placebo 150 x 14 days, followed by Placebo 250 mg BID x 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to week 4, and Baseline to week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Baseline to week 4, and Baseline to week 8

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Christine E. Marx, MD MA, Durham VA Medical Center, Durham, NC

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2013
• Primary Completion (Actual): October 10, 2018
• Study Completion (Actual): October 10, 2018

Study Registration Dates

• First Submitted: September 11, 2013
• First Submitted That Met QC Criteria: October 4, 2013
• First Posted (Estimate): October 8, 2013

Study Record Updates

• Last Update Posted (Actual): May 1, 2020
• Last Update Submitted That Met QC Criteria: April 30, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Fatigue; Musculoskeletal Pain; Pregnenolone; Gulf War Veteran; Cognitive Decline; Placebo Control
• Additional Relevant MeSH Terms: Mental Disorders; Pain; Neurologic Manifestations; Neurocognitive Disorders; Musculoskeletal Diseases; Muscular Diseases; Cognition Disorders; Fatigue; Cognitive Dysfunction; Musculoskeletal Pain
• Other Study ID Numbers: SPLD-013-12S

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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