Clinical trial NCT05623059: Evaluate Pharmacokinetics and Safety of Slow Release DHEA
Official title: Phase IIa Clinical Trial to Evaluate Pharmacokinetics and Safety of Slow Release DHEA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Asthma
Genotype
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2022-11-21
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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 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.
Primary purpose: TREATMENT

Brief summary: This is a study to look at pharmacokinetic levels of different doses of slow release DHEA in subjects with asthma.

Detailed description: Pharmacokinetic (PK) studies of DHEA in asthma 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 asthma who have the HSD3B1 AA or AC phenotypes

Eligibility criteria: Inclusion Criteria:

* Adult male or female aged between 18 and 50 at time of enrollment
* Evidence of asthma demonstrated by reversibility at visit 0 or by historical methacholine or bronchodilator reversibility if testing was performed under either the 2017 ERS technical standard (22) or the 1999 ATS Guidelines (23) 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:
* For bronchodilator reversibility: An increase in FEV1 ≥10% (24) compared to the baseline (and 200 ml) after up to 8 puffs of albuterol
* For historical methacholine responsiveness: Positive methacholine defined as PC20 ≤ 16 mg/ml, or PD20 ≤400 mcg
* Physician diagnosis of 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;
* 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)
* 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.

Primary outcomes:
measure: Determine the maximum tolerated dose for slow release DHEA in asthmatic subjects on a single and recurring regimen of 50mg and of 100mg by pharmacokinetic evaluation.
timeFrame: From baseline to 12 hours after the final dose (up to 66 days)
measure: Determine the maximum tolerated dose for slow release DHEA for asthmatic subjects on a regimen of 50mg and 100mg by adverse event evaluation.
timeFrame: From administration of the first dose to 12 hours after the final dose (up to 59 days)]
Secondary outcomes:
measure: Safety and tolerability evaluation measured by the change in vital signs from baseline to post-treatment (Vital signs will include heart-rate, respiratory rate, RA saturation)
timeFrame: From baseline to after the first washout period (up to 63 days)]
measure: Safety and tolerability evaluation measured by a change in physical symptoms from baseline to post-treatment. Physical symptoms will include reports such as cough, shortness of breath, chest tightness, wheeze)
timeFrame: From baseline to after the first washout period (up to 63 days)]
measure: Safety and tolerability evaluation measured by the change in physical exam findings from baseline to post-treatment
timeFrame: From baseline to after the first washout period (up to 63 days)
measure: Safety and tolerability evaluation measured by the change in FEV from baseline to post-treatment (as measured by spirometry).
timeFrame: From baseline to after the first washout period (up to 63 days)
measure: Safety and tolerability evaluation measured by the occurrence of an asthma exacerbation event during and after treatment.
timeFrame: From administration of the first dose to 12 hours after the final dose (up to 59 days)
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Indianapolis
country: United States
facility: University Hospital
state: Indiana
Study officials:
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