Pregnenolone + DHEA for Lower Back Pain

Overseen By Christine E Marx, MD MA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must not be taking: Narcotics, Oral contraceptives

Disqualifiers: Unstable illness, Suicidal ideation, Bipolar, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 4 weeks

108 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it requires no changes in medications less than 4 weeks before starting and no anticipated need to change psychotropic or pain medications during the 6-week study.

What evidence supports the effectiveness of the drug Pregnenolone + DHEA for lower back pain?

Research shows that DHEA can increase bone mineral density in the lumbar spine, which might help with lower back pain. Additionally, pregnenolone is involved in cell processes that could support bone health. ^{1 2 3 4 5}

How does the drug DHEA differ from other treatments for lower back pain?

DHEA is unique because it is a neurosteroid that may help modulate pain by interacting with specific receptors in the brain, such as GABA and NMDA receptors, which are involved in pain perception. This mechanism is different from traditional pain medications that typically target inflammation or pain signals directly. ^{6 7 8 9 10}

Research Team

Jennifer C Naylor, PhD

Principal Investigator

Durham VA Medical Center, Durham, NC

Christine E Marx, MD MA

Principal Investigator

Durham VA Medical Center, Durham, NC

Eligibility Criteria

This trial is for US Military Veterans aged 18-65 with chronic low back pain lasting at least 6 months, who have not changed their medications in the last 4 weeks and can commit to not altering them during the study. Participants must use birth control if applicable and cannot be pregnant or breastfeeding. Those with unstable medical conditions, recent substance abuse, or certain psychiatric diagnoses are excluded.

Inclusion Criteria

I understand and can participate in the consent process.

I am using birth control as I could get pregnant during the study.

I have had lower back pain for at least 6 months.

Exclusion Criteria

I am not pregnant or breastfeeding.

You have strong thoughts about hurting yourself or others that require immediate help.

I do not have any unstable illnesses like seizures or kidney problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Randomization/Baseline

Participants are randomized to receive pregnenolone, DHEA, or placebo and baseline measurements are taken

1 week

1 visit (in-person)

Treatment

Participants receive flexible dosing of pregnenolone, DHEA, or placebo over 4 weeks

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• DHEA
• Placebo
• Pregnenolone

Trial Overview The trial is testing Pregnenolone and DHEA—naturally occurring neurosteroids—against a placebo to see if they safely relieve chronic lower back pain without addiction risks. It's an adaptive Phase II study where participants are randomly assigned to one of these treatments.

Participant Groups

Group I: Pregnenolone Active Control 1 Intervention

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).

Group II: DHEA Active Control 1 Intervention

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).

Group III: Placebo Placebo Group 1 Intervention

Same as active comparator arms, except placebo dispensed

DHEA is already approved in United States, European Union, Canada for the following indications:

Approved in United States as DHEA for:

• Adrenal insufficiency
• Hypogonadism
• Menopause symptoms
• Anti-aging (off-label)
• Bodybuilding (off-label)

Approved in European Union as Prasterone for:

• Vulvar and vaginal atrophy

Approved in Canada as DHEA for:

• Adrenal insufficiency
• Hypogonadism

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

Pregnenolone at a dose of 10 μM was found to be optimal for promoting the proliferation of neural stem cells (NSCs), significantly increasing the number of neurospheres compared to controls.

Lower doses of pregnenolone (5 and 10 μM) enhanced NSC differentiation into oligodendrocytes, while higher doses (15 μM) promoted differentiation into neurons, indicating that pregnenolone can regulate NSC fate depending on the concentration used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnenolone enhances the proliferation of mouse neural stem cells and promotes oligodendrogenesis, together with Sox10, and neurogenesis, along with Notch1 and Pax6. Negintaji, K., Ghanbari, A., Frozanfar, M., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Endogenous DHEAS Is Causally Linked With Lumbar Spine Bone Mineral Density and Forearm Fractures in Women. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Replacement of dehydroepiandrosterone in adrenal failure: no benefit for subjective health status and sexuality in a 9-month, randomized, parallel group clinical trial. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Endocrine effects of oral dehydroepiandrosterone in men with HIV infection: a prospective, randomized, double-blind, placebo-controlled trial. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

The effect of nandrolone decanoate on bone mineral density, muscle mass, and hemoglobin levels in elderly women with osteoporosis: a double-blind, randomized, placebo-controlled clinical trial. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Pregnenolone enhances the proliferation of mouse neural stem cells and promotes oligodendrogenesis, together with Sox10, and neurogenesis, along with Notch1 and Pax6. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Influence of acute and subchronic oral administration of dehydroepiandrosterone (DHEA) on nociceptive threshold in rats. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

An exploratory pilot investigation of neurosteroids and self-reported pain in female Iraq/Afghanistan-era Veterans. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Blood Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate as Pathophysiological Correlates of Chronic Pain: Analyses Using a National Sample of Midlife Adults in the United States. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Different DHEA-S Levels and Response Patterns in Individuals with Chronic Neck Pain, Compared with a Pain Free Group-a Pilot Study. [2018]

10. England pubmed.ncbi.nlm.nih.gov

An increase in spinal dehydroepiandrosterone sulfate (DHEAS) enhances NMDA-induced pain via phosphorylation of the NR1 subunit in mice: involvement of the sigma-1 receptor. [2023]