Neurosteroids as Novel Therapeutic Agents for Chronic Pain in OEF/OIF Veterans
Condition: Lower Back Pain
MeSH terms: Chronic Pain; Low Back Pain
Intervention: Pregnenolone; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 94.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: pain; pregnenolone; Veterans; clinical trial; neurosteroid; allopregnanolone; low back; placebo controlled; randomized; musculoskeletal

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.