Neurosteroids as Novel Therapeutic Agents for Chronic Pain in OEF/OIF Veterans

Durham VA Medical Center

Status and phase: Completed; Phase 2

Conditions: Lower Back Pain

Treatments: Drug: Pregnenolone; Drug: Placebo

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT01898013

1IK2RX000908-01A1 (U.S. NIH Grant/Contract)

01710

Details and patient eligibility

About

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).

Enrollment: 94 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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94 participants in 2 patient groups, including a placebo group

Pregnenolone

Active Comparator group

Description:

Pregnenolone fixed escalating up to 500mg/day will consist of the following schedule: Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): 50mg PO, BID x 1 week, Visit 4 (week 2): 150mg PO, BID x 1 week, Visit 5 (week 3): 250mg PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered by 100mg per day and then discontinued.

Treatment:

Drug: Pregnenolone

Placebo

Placebo Comparator group

Description:

Placebo will be administered exactly the same as the active comparator (pregnenolone) and will consist of the following schedule: Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): placebo PO, BID x 1 week, Visit 4 (week 2): placebo PO, BID x 1 week, Visit 5 (week 3): placebo PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered in the exact manner as active study medication and then discontinued.

Treatment:

Drug: Placebo