Complementary Neurosteroid Intervention in Gulf War Illnesses (GWVI)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01956279

Enrollment

170

Registered

2013-10-08

Start date

2013-10-01

Completion date

2018-10-10

Last updated

2020-05-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cognitive Decline, Fatigue, Musculoskeletal Pain

Keywords

Pregnenolone, Gulf War Veteran, Fatigue, Musculoskeletal Pain, Cognitive Decline, Placebo Control

Brief summary

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.

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

40 Years to 65 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Physical Component of the SF-36	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 changes in scores represent an improvement relative to baseline.

Secondary

Measure	Time frame	Description
Brief Pain Inventory (BPI)	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.
Tower of London Test of the Brief Assessment of Cognition in Affective Disorders (BAC-A)	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.
Multidimensional Fatigue Inventory (MFI)	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 baseline.
Global Severity Index of the Symptom Checklist-90-Revised (SCL-90R)	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 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.

Countries

United States

Participant flow

Pre-assignment details

170 participants enrolled; 142 participants were randomized after a 2-week placebo lead-in phase. The remaining 28 randomized participants were withdrawn prior to week 4 post-randomization for various reasons - including medication changes during the study (exclusionary) and participants unavailable for continued contact.

Participants by arm

Arm	Count
Pregnenolone (Arm 1) Pregnenolone: Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x 28 days	82
Placebo (Arm 2) Placebo: Placebo 50mg BID x 14 days, followed by Placebo 150 x 14 days, followed by Placebo 250 mg BID x 28 days	88
Total	170

Baseline characteristics

Characteristic	Pregnenolone (Arm 1)	Placebo (Arm 2)	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	1 Participants	0 Participants	1 Participants
Age, Categorical Between 18 and 65 years	81 Participants	88 Participants	169 Participants
Age, Continuous	52.7 years STANDARD_DEVIATION 5.6	51.4 years STANDARD_DEVIATION 4.8	52.0 years STANDARD_DEVIATION 5.2
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants	1 Participants	7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	76 Participants	87 Participants	163 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	40 Participants	56 Participants	96 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	42 Participants	30 Participants	72 Participants
Region of Enrollment United States	82 Participants	88 Participants	170 Participants
Sex: Female, Male Female	10 Participants	10 Participants	20 Participants
Sex: Female, Male Male	72 Participants	78 Participants	150 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	1 / 82	0 / 88
other Total, other adverse events	69 / 82	73 / 88
serious Total, serious adverse events	1 / 82	0 / 88

Outcome results

Primary

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.