DHEA for Pulmonary Hypertension

(EDIPHY Trial)

Overseen By Rachel Sanders

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rhode Island Hospital

Must not be taking: Hormone supplements

Disqualifiers: HIV, Severe sleep apnea, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug DHEA (Dehydroepiandrosterone) can improve heart function in individuals with pulmonary arterial hypertension (PAH), a condition where high blood pressure affects the arteries in the lungs and heart. Participants will take either a DHEA tablet or a placebo pill daily for 18 weeks to determine if DHEA offers benefits over the placebo. The trial also aims to assess the safety and side effects of DHEA. It suits those diagnosed with PAH due to specific causes, such as connective tissue disease or certain drug use, and who have stable lung function without other complicating health issues. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot start new PAH therapy or change the dose significantly within 12 weeks before the trial. Also, you cannot use hormone supplements or certain hormonal therapies.

Is there any evidence suggesting that DHEA is likely to be safe for humans?

Research has shown that DHEA, a hormone treatment, is safe and well-tolerated in people with pulmonary arterial hypertension. One study found that DHEA increased certain hormone levels, but participants managed the treatment well without serious problems. Another study suggested that DHEA might benefit blood vessels and heart function. Overall, DHEA appears to be a safe treatment option, with no major safety concerns reported in current studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pulmonary hypertension?

Most treatments for pulmonary hypertension, like endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclin analogs, focus on widening blood vessels to improve blood flow. But DHEA, or dehydroepiandrosterone, works differently. It’s a natural hormone that may help reduce blood pressure in the lungs by impacting blood vessel remodeling and reducing inflammation. Researchers believe it could offer a novel approach by addressing the underlying causes of pulmonary hypertension, rather than just the symptoms. This unique mechanism is what makes DHEA an exciting potential option for patients.

What evidence suggests that DHEA might be an effective treatment for pulmonary hypertension?

Research has shown that DHEA, a natural hormone, might help with pulmonary hypertension. Some studies suggest it can prevent or reverse this condition by affecting certain processes in the body. One study noted it might reduce the strain on the heart, although results were mixed. Additionally, DHEA has improved blood vessel health and lowered inflammation in other situations. In this trial, participants will receive either DHEA or a placebo to further investigate its potential benefits for pulmonary hypertension. While the evidence is promising, more research is needed to understand its exact benefits for this condition. ^{1 2 3 5 6}

Who Is on the Research Team?

Corey E Ventetuolo, MD, MS

Principal Investigator

Brown University

Are You a Good Fit for This Trial?

This trial is for adults with pulmonary arterial hypertension, a type of high blood pressure affecting the lungs. Participants must have specific heart and lung function test results and can't be pregnant or breastfeeding, have certain cancers, severe kidney or liver disease, untreated thyroid issues, or use hormone therapies.

Inclusion Criteria

You have high blood pressure in the arteries of your lungs and high resistance in the blood vessels of your lungs.

I have been diagnosed with PAH due to genetics, a heart defect, or other specific causes.

My lung scans show moderate or less lung damage and I meet specific lung function criteria.

Exclusion Criteria

I am under 18 years old.

I started a new PAH treatment within the last 12 weeks.

I have a history of cancer in the breast, ovary, uterus, testicle, or prostate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either DHEA or placebo for 18 weeks to assess effects on RV strain and other outcomes

18 weeks

Regular visits for monitoring and assessments

Crossover

Participants switch from DHEA to placebo or vice versa for another 18 weeks

18 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Final assessment visit

What Are the Treatments Tested in This Trial?

Interventions

• DHEA
• Placebo

Trial Overview The study tests if DHEA tablets improve heart muscle function in the right ventricle compared to placebo over 18 weeks. It's a crossover trial where participants will receive both the DHEA treatment and placebo at different times to compare effects.

How Is the Trial Designed?

Group I: Placebo to DHEA Experimental Treatment 2 Interventions

1 placebo tablet taken by mouth once a day for 18 weeks, followed by 4 week washout period and then 1 DHEA tablet taken by mouth once a day for 18 weeks

Group II: DHEA to placebo Experimental Treatment 2 Interventions

DHEA tablet (50 mg) taken by mouth once a day for 18 weeks, followed by 4 week washout period and then 1 placebo tablet taken by mouth once a day for 18 weeks

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?

Rhode Island Hospital

Lead Sponsor

Trials

275

Recruited

71,400+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40766123/

A Randomized, Double-Blind, Placebo-Controlled Crossover ... Conclusions: DHEA treatment did not improve RV longitudinal strain in this pilot crossover trial but had variable and possibly beneficial ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03648385

NCT03648385 | Effects of DHEA in Pulmonary Hypertension Targeted PAH therapy leads to greater improvements in RVEF (demonstrated after just several months of treatment) in women as compared to men and partially ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8142004/

Experimental design of the Effects of Dehydroepiandrosterone ... In a randomized clinical trial (RCT) of healthy older adults, DHEA 50 mg daily improved systemic vascular stiffness and reduced levels of interleukin (IL)-6 and ...

4. pnas.org pnas.org/doi/10.1073/pnas.1633724100

Dehydroepiandrosterone (DHEA) prevents and reverses ... Our data clearly show that DHEA prevents or reverses CH-PHT development, RV hypertrophy, and PA remodeling and restores the PA contraction ...

5. ahajournals.org ahajournals.org/doi/10.1161/circ.122.suppl_21.A17741

Abstract 17741: Dehydroepiandrosterone (DHEA) ... Conclusions: We demonstrated that DHEA reverses Pulmonary Hypertension by inhibiting the Stat3/Pim1/NFATc2 axis resulting in BMPR2 upregulation.

6. atsjournals.org atsjournals.org/doi/10.1164/rccm.201512-2511ED

Estrogen: Friend or Foe in Pulmonary Hypertension? Experimental data suggest that DHEA may have beneficial vascular effects, whereas the data that DHEA improves the RV response to disease in experimental rats ...