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

NCT01898013 | Completed Phase 2 Results

• 2 other identifiers: 017101IK2RX000908-01A1
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

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).

Conditions

Lower Back Pain

Keywords

pain; pregnenolone; Veterans; clinical trial; neurosteroid; allopregnanolone; low back; placebo controlled; randomized; musculoskeletal

Outcome Measures

Primary Outcomes (1)

• Change in Pain Intensity Rating (Visit 6-Baseline)

  Weekly mean of the 24-hour average pain severity scores recorded daily on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst pain). The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores.

  Difference Scores (Visit 6-Baseline)

Secondary Outcomes (5)

• Change in Pain Interference Scores (Visit 6-Baseline)

  Difference Scores of Averaged Pain Interference Domains (Visit 6-Baseline)

• Change in Beck Depression Inventory (Visit 6-Baseline)

  Difference Scores of BDI (Visit 6-Baseline)

• Change in Davidson Trauma Scale (Visit 6-Baseline)

  Difference Scores of Total DTS Scores (Visit 6-Baseline)

• Change in Tower of London (Visit 6-Baseline)

  Difference Z-Score (Visit 6-Baseline)

• Change in Digit Sequence (Visit 6-Baseline)

  Difference Z-Scores (Visit 6-Baseline)

Study Arms (2)

Pregnenolone

ACTIVE COMPARATOR

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.

Drug: Pregnenolone

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Pregnenolone DRUG

Pregnenolone

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• OEF/OIF Veterans, 18-65 years of age, with chronic low back pain.
• 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).
• Have a weekly mean of 24-hour average pain score ≥ 4 at baseline.
• 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.
• No change in medications less than 4 weeks before baseline.
• 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).
• Ability to fully participate in the informed consent process.

You may not qualify if:

• Unstable medical or neurological illness, including seizures, renal impairment or cerebral vascular accident.
• Use of oral contraceptives or other hormonal supplements.
• Significant suicidal or homicidal ideation requiring intervention.
• Daily use of long or short-acting narcotic medications.
• 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).
• Female patients who are pregnant or breast-feeding.
• Known allergy to study medication.
• History of moderate or severe TBI (mild TBI is permissible).
• DSM-IV criteria met for alcohol and/or other substance abuse or dependence within past three months (excludes caffeine and nicotine).
• 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.
• Completion of daily diaries for less than 70% of days between Visit 1 and Visit 2 and between Visit 2 and Visit 3.
• Have ongoing or anticipated disability compensation or litigation issues, in the best judgment of the investigator.
• 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.
• 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.
• Are non-ambulatory or require the use of crutches or a walker.

Sponsors & Collaborators

• Durham VA Medical Center: lead

Study Sites (1)

Durham VA Medical Center

Durham, North Carolina, 27705, United States

Location

Related Publications (1)

• 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.

  PMID: 32119096 DERIVED

MeSH Terms

Conditions

Low Back Pain; Pain

Interventions

Pregnenolone

Condition Hierarchy (Ancestors)

Back Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Results Point of Contact

• Title: Jennifer C. Naylor, PhD
• Organization: Durham VA Medical Center

jennifer.naylor2@va.gov

9192860411

Study Officials

• Jennifer C. Naylor, PhD

  Durham VA Medical Center

  PRINCIPAL INVESTIGATOR

• Christine E Marx, MD

  Durham VA Medical Center

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2013
• First Posted: July 12, 2013
• Study Start: September 13, 2013
• Primary Completion: April 3, 2017
• Study Completion: April 3, 2017
• Last Updated: October 3, 2018
• Results First Posted: October 3, 2018

Record last verified: 2018-09

Locations

US (1)