Clinical trial NCT01898013: Neurosteroids as Novel Therapeutic Agents for Chronic Pain in OEF/OIF Veterans
Official title: Neurosteroids as Novel Therapeutic Agents for Chronic Pain in OEF/OIF Veterans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lower Back Pain
Keywords: pain
pregnenolone
Veterans
clinical trial
neurosteroid
allopregnanolone
low back
placebo controlled
randomized
musculoskeletal
Lead sponsor: Durham VA Medical Center
Sponsor class: FED
First posted: 2013-07-12
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study design is a randomized, double-blind, two-arm trial of pregnenolone and placebo to determine the possible analgesic effects in OEF/OIF Veterans with chronic low back pain. The total study duration is 6 weeks (followed by two-follow up phone calls). All patients will monitor pain symptoms for one week with pain diaries, followed by a 1-week placebo-only lead-in period, 90 subjects will be randomly assigned to one of two groups. Of these subjects, 45 subjects will receive pregnenolone, and 45 subjects will receive placebo for 4 weeks. Patient interview assessments and laboratory studies will be performed at each interview time point. Pregnenolone, allopregnanolone and other neurosteroid metabolites will be determined by gas chromatography / mass spectrometry (GC/MS), proceeded by high performance liquid chromatography (HPLC).


Eligibility criteria: Inclusion Criteria:

1. OEF/OIF Veterans, 18-65 years of age, with chronic low back pain.
2. Based on medical history and medical records, have low back pain (Thoracic Vertebrae 6 or below) present on most days for the preceding 6 months or longer, and fulfill all disease diagnostic criteria (please see disease diagnostic criteria below).
3. Have a weekly mean of 24-hour average pain score ≥ 4 at baseline.
4. Negative pregnancy test if female. Sexually active subjects are required to use a medically acceptable form of birth control if they are of childbearing potential and could become pregnant during the study. A medically acceptable form of birth control includes non-hormonal intrauterine devices, surgical sterilization, or double barrier methods (e.g., diaphragm with contraceptive jelly, condom with contraceptive foam, cervical caps with contraceptive jelly). Sexual abstinence with agreement to continue abstinence or to use a medically acceptable method of contraception (as listed above) should sexual activity occur is permissible.
5. No change in medications less than 4 weeks before baseline.
6. No anticipated need to alter psychotropic or pain medications for the 6-wk study duration (as determined by study physician's review of records and/or discussion with prescribing physician).
7. Ability to fully participate in the informed consent process.

Exclusion Criteria:

1. Unstable medical or neurological illness, including seizures, renal impairment or cerebral vascular accident.
2. Use of oral contraceptives or other hormonal supplements.
3. Significant suicidal or homicidal ideation requiring intervention.
4. Daily use of long or short-acting narcotic medications.
5. Current Diagnostic and Statistical Manual (DSM-IV) diagnosis of bipolar disorder, schizophrenia, or other psychotic disorder, or cognitive disorder due to a general medical condition (other than if related to mild TBI).
6. Female patients who are pregnant or breast-feeding.
7. Known allergy to study medication.
8. History of moderate or severe TBI (mild TBI is permissible).
9. DSM-IV criteria met for alcohol and/or other substance abuse or dependence within past three months (excludes caffeine and nicotine).
10. Have received epidural steroids, facet block, nerve block, or other invasive procedures aimed to reduce low back pain within the past 3 months prior to Visit 1.
11. Completion of daily diaries for less than 70% of days between Visit 1 and Visit 2 and between Visit 2 and Visit 3.
12. Have ongoing or anticipated disability compensation or litigation issues, in the best judgment of the investigator.
13. Have a presence of any factors/conditions, medical or other, that in the judgment of the investigator may interfere with performance of study outcome measures, such as treatment-refractory history.
14. Have serious or unstable cardiovascular, hepatic, renal, metabolic, respiratory, or hematologic illness, symptomatic peripheral vascular disease, or other medical condition or psychiatric conditions that, in the opinion of investigator and study physician, would compromise participation or be likely to lead to hospitalization during the course of the study.
15. Are non-ambulatory or require the use of crutches or a walker.
16. Current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern, or history of suicide attempt in the past 3 years.

Primary outcomes:
measure: Change in Pain Intensity Rating (Visit 6-Baseline)
timeFrame: Difference Scores (Visit 6-Baseline)
Secondary outcomes:
measure: Change in Pain Interference Scores (Visit 6-Baseline)
timeFrame: Difference Scores of Averaged Pain Interference Domains (Visit 6-Baseline)
measure: Change in Beck Depression Inventory (Visit 6-Baseline)
timeFrame: Difference Scores of BDI (Visit 6-Baseline)
measure: Change in Davidson Trauma Scale (Visit 6-Baseline)
timeFrame: Difference Scores of Total DTS Scores (Visit 6-Baseline)
measure: Change in Tower of London (Visit 6-Baseline)
timeFrame: Difference Z-Score (Visit 6-Baseline)
measure: Change in Digit Sequence (Visit 6-Baseline)
timeFrame: Difference Z-Scores (Visit 6-Baseline)
Other outcomes:
Locations:
city: Durham
country: United States
facility: Durham VA Medical Center
state: North Carolina
Study officials:
affiliation: Durham VA Medical Center
name: Jennifer C. Naylor, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Durham VA Medical Center
name: Christine E Marx, MD
role: STUDY_DIRECTOR
References:
citation: Naylor JC, Kilts JD, Shampine LJ, Parke GJ, Wagner HR, Szabo ST, Smith KD, Allen TB, Telford-Marx EG, Dunn CE, Cuffe BT, O'Loughlin SH, Marx CE. Effect of Pregnenolone vs Placebo on Self-reported Chronic Low Back Pain Among US Military Veterans: A Randomized Clinical Trial. JAMA Netw Open. 2020 Mar 2;3(3):e200287. doi: 10.1001/jamanetworkopen.2020.0287.