Evaluate Pharmacokinetics and Safety of Slow Release DHEA

Study Overview
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Brief Summary
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This is a study to look at pharmacokinetic levels of different doses of slow release DHEA in subjects with severe asthma.

Detailed Description
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Pharmacokinetic (PK) studies of DHEA in asthma in general, and severe asthma in particular, have never been done. In many diseases, PK in subjects with disease differs from that of control subjects and those with other conditions. Therefore, researchers are investigating if PK levels of slow release DHEA are different in subjects with severe asthma who have the HSD3B1 AA or AC phenotypes

Official Title
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Phase IIa Clinical Trial to Evaluate Pharmacokinetics and Safety of Slow Release DHEA

Conditions
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Asthma, Genotype

Intervention / Treatment
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* Drug: Slow Release DHEA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male or female aged between 18 and 50 at time of enrollment Evidence of asthma demonstrated by either bronchodilator reversibility or methacholine responsiveness either during the run-in or by historical evidence of either criterion if testing was performed under either the 2017 ERS technical standard or the 1999 ATS Guidelines or outside studies, provided that full sets of flow volume loops have been reviewed and approved by the PI. These criteria are defined as one of the following: increase in FEV1 less than or equal to 12 percent and 200 ml after up to 8 puffs of albuterol; positive methacholine defined as PC20 greater than or equal to 16mg/ml, or PD20 greater than or equal to 400 mcg; documented physician diagnosis of severe asthma according to NHLBI guidelines; Consistent use of an ICS/LABA inhaler for the prior 2 months; Non smoker; females must not be pregnant or lactating; absence of non-allergic comorbidities; baseline DHEA-S concentration < 45 μg/dL in females and < 90 μg/dL in males; genotype testing positive for either HSD3B1 AA or AC specific variant Exclusion Criteria: Pregnant or actively trying to become pregnant; breastfeeding positive urine pregnancy test Known lung disease other than asthma Acute (non asthma-related) dyspnea, viral respiratory illness or asthma exacerbation within 4 weeks of screening Systemic glucocorticoid dosing for maintenance >10 mg/day of prednisone or equivalent Patients with significant non-allergic comorbidities (e.g. cerebral palsy, heart disease, kidney disease, liver disease, etc.) Patients with any know central or peripheral endocrine abnormality such as precocious puberty or diabetes Patients with any known previous adverse reaction to DHEA Current smoker or pack year history > 5 years (includes vaping/nicotine inhalation devices) Positive urine cotinine test (> 100 mg/mL) Use of prednisone or antibiotics in the last 4 weeks Use of any performance-enhancing drugs in the last 2 weeks Use of DHEA in the last 2 weeks Androgen use for any reason HSD3B1 CC phenotype Any other condition or finding that would compromise the safety of the subject or the quality of the study data, or otherwise interfere with achieving the study objectives, as determined by the PI Menopausal amenorrhea by history Positive PSA (>4 ng/ml) (Prostate Specific Antigen) Patients on biologic treatments for asthma Prior diagnosis of vocal cord dysfunction, bronchopulmonary dysplasia, cystic fibrosis, chronic obstructive pulmonary disorder, or other lung disease Systolic blood pressure > 150 mm Hg and/or diastolic blood pressure >90 mm Hg Heart rates outside the range of 50 to 120 beats per minutes or with a pathologic irregularity Patients afflicted 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This is an unblinded pharmacokinetic (PK) study to determine optimal dosing for future studies. This study 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 severe asthma and serum DHEA-S <90 μg/dL in men and <45 μg/dL in women. 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 50mg dose<br>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 severe asthma and serum DHEA-S <90 μg/dL in men and <45 μg/dL in women. 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. | Drug: Slow Release DHEA<br>* DHEA is a hormone produced by the body's adrenal gland. In drug form, it is available as an over-the-counter supplement that is available on the market without prescription.<br>* Other names: Slow Release Dehydroepiandrosterone;|
| Other: 100mg dose<br>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 severe asthma and serum DHEA-S <90 μg/dL in men and <45 μg/dL in women. 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. | Drug: Slow Release DHEA<br>* DHEA is a hormone produced by the body's adrenal gland. In drug form, it is available as an over-the-counter supplement that is available on the market without prescription.<br>* Other names: Slow Release Dehydroepiandrosterone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the dose level to be used in patients | Objective is to determine the dose of slow release DHEA in patients with severe asthma and AA or AC genotype in conjunction with low serum DHEA-s. | within 9 months of all subjects completing study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pulse rate from baseline to post-treatment | Objective is to evaluate the safety and tolerability of DHEA in asthma by measuring the change in pulse rate from before treatment to after treatment. | from baseline through treatment completion, approximately 12 hours | 
| Change in pulse oximetry from baseline to post-treatment | Objective is to evaluate the safety and tolerability of DHEA in asthma by measuring the change in pulse oximetry from before treatment to after treatment. | from baseline through treatment completion, approximately 12 hours | 
| Change in respiratory rate from baseline to post-treatment | Objective is to evaluate the safety and tolerability of DHEA in asthma by measuring the change in respiration rate from before treatment to after treatment. | from baseline through treatment completion, approximately 12 hours | 
| Change in blood pressure from baseline to post-treatment | Objective is to evaluate the safety and tolerability of DHEA in asthma patients by measuring the change in blood pressure from before treatment to after treatment. | from baseline through treatment completion, approximately 12 hours | 
| Change in physical exam results from baseline to post-treatment | Objective is to evaluate the safety and tolerability of DHEA in asthma patients by measuring changes in results of a standard-of-care physical exam performed by a physician. | from baseline through treatment completion, approximately 12 hours | 
| Development of physical symptoms after treatment | Objective is to evaluate the safety and tolerability of DHEA in asthma patients by physical symptom monitoring - coordinator will be attentive to any respiratory responses or other physical responses following the treatment. | from baseline through treatment completion, approximately 12 hours | 
| Development of adverse events and serious adverse events | Objective is to evaluate the safety and tolerability of DHEA in asthma patients by monitoring for adverse event and serious adverse event monitoring as defined by FDA. | from baseline through treatment completion, approximately 12 hours | 
| Change in DHEA levels in blood from baseline to post-treatment | Objective is to evaluate the safety and tolerability of DHEA in asthma patients by evaluating DHEA levels in blood drawn from subject after DHEA treatment. | from baseline through treatment completion, approximately 12 hours | 
| Change in FEV from baseline to post-treatment as measured by spirometry | Objective is to evaluate the safety and tolerability of DHEA in asthma patients by performing pulmonary function test to obtain measurements of FEV (forced expiratory volume) in the patient. | from baseline through treatment completion, approximately 12 hours | 
| Occurrence of an asthma exacerbation event | Objective is to evaluate the safety and tolerability of DHEA in asthma patients by recording any instance of asthma exacerbation event following the treatment. | from baseline through treatment completion, approximately 12 hours |