Investigating Novel Interventions for Low Back Pain in US Military Veterans: A Randomized Controlled Adaptive Phase II Trial

NCT05935761 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: NURP-004-22FI01CX002667-01
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic pain symptoms are very common among U.S. Military Veterans and have a profound negative impact on mental health symptoms and quality of life, in addition to increasing risk for suicidal ideation and suicidal behaviors. There are currently extremely few safe and effective pharmacological treatments for chronic pain disorders, and the clinical need to develop new therapeutics for pain has never been more urgent. Fueled by the worsening opioid crisis and further exacerbated by the COVID-19 pandemic, opioid and other drug overdose deaths have climbed to staggeringly high levels. The rapid development of medications for the management of chronic pain conditions that are safe, well-tolerated, efficacious and non-addicting is thus of paramount importance. The two neurosteroid candidates to be investigated in this trial are naturally occurring molecules enriched in human brain and potentially ideal candidates for safe and effective chronic pain treatment.

Conditions

Chronic Low Back Pain

Keywords

neurosteroid; pregnenolone; DHEA; Veteran; Pain; Back

Outcome Measures

Primary Outcomes (1)

• Pain Numerical Rating Scale (0-10) Change

  Weekly mean of the 24-hour average pain severity scores recorded daily on an 11-point numerical rating scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain).

  Visit 1 (Week 1/screening), Visit 2 (Week 2/Randomization/Baseline), Visit 3 (Week 3), Visit 4 (Week 4), Visit 5 (Week 5), Visit 6 (Week 6)

Secondary Outcomes (1)

• Brief Pain Inventory

  Visit 1 (Week 1/screening), Visit 2 (Week 2/Randomization/Baseline), Visit 3 (Week 3), Visit 4 (Week 4), Visit 5 (Week 5), Visit 6 (Week 6)

Other Outcomes (2)

• Beck Depression Inventory, 2nd Edition

  Visit 1 (Week 1/screening), Visit 2 (Week 2/Randomization/Baseline), Visit 3 (Week 3), Visit 4 (Week 4), Visit 5 (Week 5), Visit 6 (Week 6)

• PTSD-Checklist 5

  Visit 1 (Week 1/screening), Visit 2 (Week 2/Randomization/Baseline), Visit 3 (Week 3), Visit 4 (Week 4), Visit 5 (Week 5), Visit 6 (Week 6)

Study Arms (3)

Pregnenolone

ACTIVE COMPARATOR

Pregnenolone dosing will begin at 500mg/day x 7 days, and will increase by 500mg each following week as tolerated (to a potential maximum dose 2000mg/day).

Drug: Pregnenolone

DHEA

ACTIVE COMPARATOR

DHEA dosing will begin at 100mg/day x 7 days, and will increase by 100mg each following week as tolerated (to a potential maximum dose 400mg/day).

Drug: DHEA

Placebo

PLACEBO COMPARATOR

Same as active comparator arms, except placebo dispensed

Drug: Placebo

Interventions

Pregnenolone DRUG

Pregnenolone dosing will begin at 500mg/day x 7 days, and will increase by 500mg each following week as tolerated (to a potential maximum dose 2000mg/day).

Pregnenolone

DHEA DRUG

DHEA dosing will begin at 100mg/day x 7 days, and will increase by 100mg each following week as tolerated (to a potential maximum dose 400mg/day).

DHEA

Placebo DRUG

Same as active comparator arms, except placebo dispensed

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:

• 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 (CVA).
• Use of oral contraceptives or other hormonal supplements-this is out of caution, as it is unknown if the study medications would impact the efficacy of hormonal contraception.
• Significant suicidal or homicidal ideation that necessitates intervention.
• Daily use of long or short-acting narcotic medications (PRN use will be considered).
• Current DSM-5 diagnosis of bipolar disorder, schizophrenia, or other psychotic disorder, or cognitive disorder due to a general medical condition.
• Female participants who are pregnant or breast-feeding.
• Known allergy to study medication.
• History of moderate or severe TBI (mild TBI is permissible).
• DSM-5 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.
• 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 study.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Durham VA Medical Center, Durham, NC

Durham, North Carolina, 27705-3875, United States

Location

MeSH Terms

Conditions

Pain

Interventions

Pregnenolone; Dehydroepiandrosterone

Condition Hierarchy (Ancestors)

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; Androstenols; Androstenes; Androstanes; 17-Ketosteroids; Ketosteroids; Testosterone Congeners

Study Officials

• Jennifer C Naylor, PhD

  Durham VA Medical Center, Durham, NC

  PRINCIPAL INVESTIGATOR

• Christine E. Marx, MD MA

  Durham VA Medical Center, Durham, NC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christine E Marx, MD MA

CONTACT

(919) 286-0411; christine.marx@va.gov

Jennifer C Naylor, PhD

CONTACT

(919) 286-0411; jennifer.naylor2@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded study, all are blinded except for the research pharmacist who creates the randomization schedule.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo controlled trial.

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: July 7, 2023
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)