Slow Release DHEA for Asthma

(DHEA Trial)

Recruiting at 1 trial location

Overseen By Kenzie Mahan

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Indiana University

Must be taking: ICS/LABA inhaler

Must not be taking: Prednisone, Androgens, DHEA

Disqualifiers: Pregnancy, Lung disease, Heart disease, Diabetes, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 days per cycle, with a 7-day washout period

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new slow-release form of DHEA, a hormone, to observe its movement through the body in people with asthma. Researchers are evaluating two different doses to determine how much DHEA remains in the blood over time. The trial targets adults diagnosed with asthma who regularly use an inhaler and have a specific genetic profile. Participants must also be non-smokers with no other lung diseases. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new form of DHEA.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you must have been using an ICS/LABA inhaler consistently for the past 2 months. You cannot have used prednisone, antibiotics, performance-enhancing drugs, or DHEA in the last few weeks.

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

Research has shown that slow-release DHEA has potential for treating asthma, demonstrating promising safety results. In one study, patients using a mist form of DHEA-3-sulfate (a type of DHEA) experienced better asthma control with few side effects. Importantly, no changes in sex hormones occurred, addressing concerns often associated with steroid treatments.

Another study found that DHEA might improve lung function in women with asthma. These findings suggest that slow-release DHEA is generally well-tolerated. However, the treatment remains in the early stages of testing, and researchers continue to gather more safety information. For questions or concerns, consulting a doctor is advisable. ^{1 2 3 4 5}

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

Researchers are excited about slow-release DHEA for asthma because it's a fresh approach that could offer new benefits over traditional treatments like inhaled corticosteroids or bronchodilators. Unlike these standard therapies, which primarily target inflammation and airway constriction, slow-release DHEA introduces a novel delivery system that may help regulate hormone levels in the body. This unique mechanism could potentially address asthma symptoms differently, providing an alternative for patients who don't respond well to conventional medications. Plus, the slow-release capsules ensure a sustained effect, possibly leading to more consistent control of asthma symptoms with fewer doses.

What evidence suggests that slow release DHEA might be an effective treatment for asthma?

Research has shown that slow-release DHEA, which participants in this trial will receive, might help people with asthma. One study found that 59.4% of patients taking DHEA noticed symptom improvement, compared to 45.7% of those taking a placebo (a pill with no active ingredient). This suggests DHEA could help some people breathe easier. Early findings also indicate that DHEA can reduce inflammation, which is important for managing asthma. Additionally, DHEA might improve lung function, especially in women with low levels of a related steroid called DHEAS. These results suggest DHEA could be a helpful option for better asthma control. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults aged 18-50 with severe asthma, demonstrated by specific tests or a physician's diagnosis according to NHLBI guidelines. Participants must be non-smokers, not pregnant or lactating, and have been on consistent asthma medication for the past two months. They should have low baseline DHEA-S levels and test positive for certain genetic variants.

Inclusion Criteria

Absence of non-allergic comorbidities

Non-smoker

I have been using an ICS/LABA inhaler regularly for the last 2 months.

Exclusion Criteria

Patients with any known previous adverse reaction to DHEA

Positive urine pregnancy test

Patients with any additional acute or chronic pathology that in the opinion of the screening physician makes them unsuitable for study or increases the risks associated with the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time dose followed by twice daily dosing of slow release DHEA for 3 days, with a washout period and repeat with a higher dose

6 days per cycle, with a 7-day washout period

Multiple visits for dosing and PK sampling

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and changes in pulmonary function

Up to 66 days

What Are the Treatments Tested in This Trial?

Interventions

• Slow Release DHEA

Trial Overview The trial is testing how different doses of slow release DHEA are processed in the body (pharmacokinetics) in subjects with severe asthma. The goal is to understand how this treatment affects individuals with specific genotypes.

How Is the Trial Designed?

Group I: 50mg dose Experimental Treatment 1 Intervention

This arm will start with a one-time dose and progress to twice daily dosing for 3 days, every 12 hours. Study cohort will be 9 subjects with asthma. DHEA dose will be 50 mg via slow release capsules. Endpoints will be serum DHEA and DHEA-S levels at 10, 20, 30, 60 min \& 2, 4, 6, 8, 12h after administration. After a one-week washout period, the protocol will be repeated using 100 mg of SR-DHEA.

Group II: 100mg dose Experimental Treatment 1 Intervention

This arm will start with a one-time 100mg dose and progress to twice daily dosing for 3 days, every 12 hours. Study cohort will be same 9 subjects with asthma. DHEA dose will be 100mg via slow release capsules. Endpoints will be serum DHEA and DHEA-S levels at 10, 20, 30, 60 min \& 2, 4, 6, 8, 12h after administration.

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

Approved in United States as Intrarosa for:

• Moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause

Approved in European Union as Prasterone for:

• Vulvar and vaginal atrophy

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

DHEA has the potential to improve asthma treatment by reversing cytokine imbalances and reducing allergic inflammation in the airways, making it a promising alternative to traditional glucocorticoids.

Unlike glucocorticoids, DHEA does not have undesirable side effects and may help patients who are resistant to corticosteroids, offering a steroid-sparing effect for those on high doses of glucocorticoids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asthma and dehydroepiandrosterone (DHEA): facts and hypotheses. Kasperska-Zajac, A.[2021]

In a study of 108 patients with bronchial asthma, men had significantly higher levels of the adrenal androgen dehydroepiandrosterone sulfate (DHEAS) compared to women, which may influence asthma severity.

Lower serum DHEAS levels were associated with reduced forced expiratory volume in 1 second (FEV1), indicating that patients with severe asthma and low DHEAS may experience more frequent and prolonged asthma attacks, and show limited improvement in lung function with bronchodilator therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[External respiratory function and adrenal androgenic function in patients with bronchial asthma]. Charikova, EI., Shutov, AM.[2013]

Prasterone (DHEA) replacement therapy at a daily dose of 50 mg effectively raises plasma DHEAS levels to normal, showing beneficial effects on mood, fatigue, general well-being, and sexual function in patients with adrenocortical insufficiency.

The treatment appears to have moderate and acceptable androgenic side effects on skin and hair, making it a justifiable option for patients who do not fully respond to standard glucocorticosteroid therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of prasterone (dehydroepiandrosterone) in substitution therapy for adrenocortical insufficiency]. Zelissen, PM., Thijssen, JH.[2013]

Inhaled dehydroepiandrosterone-3-sulfate (DHEAS) significantly improved asthma control in patients with moderate-to-severe asthma, as evidenced by a notable reduction in Asthma Control Questionnaire (ACQ) scores after 6 weeks of treatment.

The safety profile of inhaled DHEAS was favorable, with fewer respiratory-related withdrawals and minimal adverse events, indicating it may be a safe addition to asthma management without affecting sex hormone levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nebulized dehydroepiandrosterone-3-sulfate improves asthma control in the moderate-to-severe asthma results of a 6-week, randomized, double-blind, placebo-controlled study. Wenzel, SE., Robinson, CB., Leonard, JM., et al.[2016]

DHEA significantly suppresses the production of key cytokines (IL-5, IL-10, and IFN-gamma) in peripheral blood mononuclear cells from asthmatic patients, indicating its potential to reduce allergic inflammation in asthma.

The effectiveness of DHEA in suppressing cytokine production is greater in patients with airway hyperresponsiveness (AHR), suggesting that it may be particularly beneficial for those with more severe asthma symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of dehydroepiandrosterone on Th2 cytokine production in peripheral blood mononuclear cells from asthmatics. Choi, IS., Cui, Y., Koh, YA., et al.[2021]

In a study using a dust mite-induced asthma model with BALB/c mice, dehydroepiandrosterone (DHEA) significantly reduced established allergic airway inflammation and blood eosinophilia after treatment, indicating its potential as a therapeutic agent.

The reduction in inflammation was linked to decreased levels of key inflammatory cytokines (interleukin-4, interleukin-5, and interferon-gamma), suggesting that DHEA modulates the immune response in allergic conditions, although it did not affect total immunoglobulin E levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dehydroepiandrosterone attenuates allergic airway inflammation in Dermatophagoides farinae-sensitized mice. Yu, CK., Liu, YH., Chen, CL.[2015]

Dehydroepiandrosterone (DHEA) effectively reduces airway hyperresponsiveness and lung eosinophil infiltration in ovalbumin-sensitized asthmatic mice, suggesting its potential as an anti-inflammatory treatment for asthma.

The mechanism of action involves the inhibition of proinflammatory cytokines and chemokines, such as IL-6, IL-8, CCL11, and CCL24, indicating that DHEA may modulate immune responses by suppressing Th2-associated inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dehydroepiandrosterone suppresses eosinophil infiltration and airway hyperresponsiveness via modulation of chemokines and Th2 cytokines in ovalbumin-sensitized mice. Liou, CJ., Huang, WC.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07179952

NCT07179952 | Efficacy and Safety of Slow Release DHEA Determine if slow-release DHEA in patients with asthma improves asthma control based on ACT (Asthma Control Test) scoring. Results will be between 0-25. 20-25: ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05623059

Evaluate Pharmacokinetics and Safety of Slow Release ... The objective is to evaluate the safety and tolerability of slow release DHEA in asthma patients by performing pulmonary function testing to obtain measurements ...

3. withpower.com withpower.com/trial/phase-2-asthma-11-2022-d7333

Slow Release DHEA for Asthma · Info for Participants Specifically, 59.4% of patients in the DHEAS group experienced a noticeable improvement in their symptoms, compared to 45.7% in the placebo group. This suggests ...

4. iu.flintbox.com iu.flintbox.com/technologies/4a995fc1-912f-4d56-aafb-df326859bcb6

Treatment of Asthma with Novel Formulation of DHEA Preliminary data are consistent with murine data in suggesting that DHEA has important anti-inflammatory effects in asthma, and that it is well ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6967310/

Dehydroepiandrosterone Supplementation May Benefit ... Our results suggest that the over-the-counter steroid DHEA may improve lung function in asthma outcomes among women with DHEAS < 200 ug/dL.

6. researchgate.net researchgate.net/publication/41657804_Asthma_and_Dehydroepiandrosterone_DHEA_Facts_and_Hypotheses

Asthma and Dehydroepiandrosterone (DHEA): Facts and ... DHEA is able to reverse cytokine imbalances associated with asthma, may prevent and attenuate allergic inflammation in airways, and does not ...

7. atsjournals.org atsjournals.org/doi/10.1164/rccm.202009-3720OC

Benefits of Airway Androgen Receptor Expression in ... In a pilot study, dehydroepiandrosterone (DHEA) supplementation in women with asthma with low DHEA sulfate (DHEA-S) levels may benefit lung ...