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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two natural molecules, Pregnenolone and DHEA (Dehydroepiandrosterone), to determine their effectiveness in reducing chronic lower back pain. Researchers seek new, safe, and effective treatments for chronic pain, particularly for Veterans who often face pain impacting their mental health and quality of life. Participants will receive either Pregnenolone, DHEA, or a placebo (a non-active substance) to compare the treatments' effectiveness. Veterans experiencing lower back pain on most days for at least six months, with no recent changes in pain medication, might be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to developing potentially effective pain relief solutions.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pregnenolone and DHEA are generally safe for humans, but important details require consideration. Pregnenolone, a natural hormone in the body, aids in producing other hormones. It is usually well-tolerated, though limited research exists on its safety specifically for pain management.

For DHEA, studies suggest it is likely safe for short-term use. It has been used safely in doses up to 50 mg daily for up to two years. However, the higher doses used in this trial (up to 400 mg per day) have not been as well-studied, so caution is advised. Some side effects may include changes in hormone levels, which can affect individuals differently.

This trial is in an early stage and aims to learn more about the safety and effectiveness of these treatments for chronic lower back pain. Prospective participants should consult a healthcare provider about the possible risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because pregnenolone and DHEA offer a fresh approach to tackling lower back pain. Unlike standard treatments like NSAIDs, opioids, or physical therapy, which mainly address symptoms, pregnenolone and DHEA focus on hormonal pathways that might influence pain perception and inflammation. Pregnenolone is a precursor to various hormones, potentially providing a broader impact on pain modulation, while DHEA is known for its role in reducing inflammation and improving mood. These unique mechanisms could offer new hope for those seeking alternatives to conventional pain management strategies.

What evidence suggests that this trial's treatments could be effective for lower back pain?

This trial will compare the effects of Pregnenolone and DHEA on lower back pain. Research has shown that pregnenolone, which participants in this trial may receive, can help reduce chronic low back pain in veterans. Specifically, studies found that those taking pregnenolone reported a significant decrease in pain compared to those taking a placebo. After four weeks, veterans noticed clear relief from their pain symptoms.

In contrast, DHEA (dehydroepiandrosterone), another treatment option in this trial, has shown potential benefits in animal studies, where it helped reduce pain sensitivity. Although limited human data exists on DHEA’s effect on chronic pain, it might help by altering how the body processes pain signals.

In summary, pregnenolone has been effective in reducing chronic pain in people, while DHEA shows promise based on early animal studies. ^{5 6 7 8 9}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2677000/

Dehydroepiandrosterone replacement therapy in older adults Outcomes from the 1-y randomized controlled trial​​ In men, lumbar spine BMD increased by 1.7 ± 0.3% in the DHEA group and by 1.1 ± 0.3% in the placebo group (P ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2435090/

Effect of dehydroepiandrosterone supplementation on ... After 12 months, there was a positive effect of DHEA on lumbar spine BMD in women (p=0.03), but no effect was observed for hip, femoral neck or total body BMD, ...

3. clinicalpainadvisor.com clinicalpainadvisor.com/news/dhea-or-dhea-s-may-be-biomarkers-for-chronic-pain-among-women/

Chronic Pain Associated With Lower Serum DHEA-S ... Sulfated dehydroepiandrosterone (DHEA-S) concentrations in blood serum were reduced among women with chronic pain.

4. mdpi.com mdpi.com/2079-9721/13/2/42

The Role of Cortisol and Dehydroepiandrosterone in ... Kibaly et al. demonstrated that DHEA administration reduced mechanical hypersensitivity in a mouse model of neuropathic pain. The analgesic effects were ...

5. midus.wisc.edu midus.wisc.edu/findings/pdfs/2236.pdf

Blood Dehydroepiandrosterone and ... - MIDUS At the dorsal horn of the spinal cord, DHEA/-S may suppress pain signal transduction through androgenic metabolism and complex effects on N ...

6. mayoclinic.org mayoclinic.org/drugs-supplements-dhea/art-20364199

DHEA Safety and side effects. DHEA is a hormone. Use of this supplement might increase levels of androgen and have a steroid effect. DHEA also might increase the ...

7. webmd.com webmd.com/vitamins/ai/ingredientmono-331/dhea

Dhea - Uses, Side Effects, and More When taken by mouth: DHEA is possibly safe when used short-term. DHEA has been used safely for up to 2 years, usually in doses of 50 mg daily. DHEA side effects ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK279006/

Adrenal Androgens and Aging - Endotext - NCBI Bookshelf - NIH DHEA supplements were taken off the U.S. market in 1985 because of their unproven safety and effectiveness, but were reintroduced as a dietary ...

9. webmd.com webmd.com/diet/dhea-supplements

DHEA Supplements: Health Benefits, Uses, and Side Effects We need more research to know whether DHEA supplements are safe. The FDA has only approved one form of DHEA to treat menopause symptoms.