Evaluate Pharmacokinetics and Safety of Slow Release DHEA

Asthma Clinical Trial

— DHEA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05623059
• Other study ID #: 15038
• Secondary ID: P01HL158507
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 3, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: Indiana University
• Contact: Kenzie Mahan
• Phone: 3172748899
• Email: krmahan[@]iu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 27
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma
• Genotype

Intervention

Drug:
• Slow Release DHEA
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.

Locations

Country	Name	City	State
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University Hospital	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (25)

Al-Tarrah K, Moiemen N, Lord JM. The influence of sex steroid hormones on the response to trauma and burn injury. Burns Trauma. 2017 Sep 14;5:29. doi: 10.1186/s41038-017-0093-9. eCollection 2017. — View Citation

Bentley JK, Hershenson MB. Airway smooth muscle growth in asthma: proliferation, hypertrophy, and migration. Proc Am Thorac Soc. 2008 Jan 1;5(1):89-96. doi: 10.1513/pats.200705-063VS. — View Citation

Bulitta JB, Jiao Y, Drescher SK, Oliver A, Louie A, Moya B, Tao X, Wittau M, Tsuji BT, Zavascki AP, Shin BS, Drusano GL, Sorgel F, Landersdorfer CB. Four Decades of beta-Lactam Antibiotic Pharmacokinetics in Cystic Fibrosis. Clin Pharmacokinet. 2019 Feb;58(2):143-156. doi: 10.1007/s40262-018-0678-x. — View Citation

Carraro S, Doherty J, Zaman K, Gainov I, Turner R, Vaughan J, Hunt JF, Marquez J, Gaston B. S-nitrosothiols regulate cell-surface pH buffering by airway epithelial cells during the human immune response to rhinovirus. Am J Physiol Lung Cell Mol Physiol. 2006 May;290(5):L827-32. doi: 10.1152/ajplung.00406.2005. — View Citation

Chang KH, Li R, Kuri B, Lotan Y, Roehrborn CG, Liu J, Vessella R, Nelson PS, Kapur P, Guo X, Mirzaei H, Auchus RJ, Sharifi N. A gain-of-function mutation in DHT synthesis in castration-resistant prostate cancer. Cell. 2013 Aug 29;154(5):1074-1084. doi: 10.1016/j.cell.2013.07.029. — View Citation

Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, Adcock IM, Bateman ED, Bel EH, Bleecker ER, Boulet LP, Brightling C, Chanez P, Dahlen SE, Djukanovic R, Frey U, Gaga M, Gibson P, Hamid Q, Jajour NN, Mauad T, Sorkness RL, Teague WG. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014 Feb;43(2):343-73. doi: 10.1183/09031936.00202013. Epub 2013 Dec 12. Erratum In: Eur Respir J. 2014 Apr;43(4):1216. Dosage error in article text. Eur Respir J. 2018 Jul 27;52(1): Eur Respir J. 2022 Jun 9;59(6): — View Citation

Coates AL, Wanger J, Cockcroft DW, Culver BH; Bronchoprovocation Testing Task Force: Kai-Hakon Carlsen; Diamant Z, Gauvreau G, Hall GL, Hallstrand TS, Horvath I, de Jongh FHC, Joos G, Kaminsky DA, Laube BL, Leuppi JD, Sterk PJ. ERS technical standard on bronchial challenge testing: general considerations and performance of methacholine challenge tests. Eur Respir J. 2017 May 1;49(5):1601526. doi: 10.1183/13993003.01526-2016. Print 2017 May. — View Citation

Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, MacIntyre NR, McKay RT, Wanger JS, Anderson SD, Cockcroft DW, Fish JE, Sterk PJ. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med. 2000 Jan;161(1):309-29. doi: 10.1164/ajrccm.161.1.ats11-99. No abstract available. — View Citation

Gaston B, Reilly J, Drazen JM, Fackler J, Ramdev P, Arnelle D, Mullins ME, Sugarbaker DJ, Chee C, Singel DJ, Loscalzo J, Stamler JS. Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10957-61. doi: 10.1073/pnas.90.23.10957. — View Citation

Gaston B, Sears S, Woods J, Hunt J, Ponaman M, McMahon T, Stamler JS. Bronchodilator S-nitrosothiol deficiency in asthmatic respiratory failure. Lancet. 1998 May 2;351(9112):1317-9. doi: 10.1016/S0140-6736(97)07485-0. — View Citation

Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, Hallstrand TS, Kaminsky DA, McCarthy K, McCormack MC, Oropez CE, Rosenfeld M, Stanojevic S, Swanney MP, Thompson BR. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med. 2019 Oct 15;200(8):e70-e88. doi: 10.1164/rccm.201908-1590ST. — View Citation

Hall SL, Baker T, Lajoie S, Richgels PK, Yang Y, McAlees JW, van Lier A, Wills-Karp M, Sivaprasad U, Acciani TH, LeCras TD, Myers JB, Kovacic MB, Lewkowich IP. IL-17A enhances IL-13 activity by enhancing IL-13-induced signal transducer and activator of transcription 6 activation. J Allergy Clin Immunol. 2017 Feb;139(2):462-471.e14. doi: 10.1016/j.jaci.2016.04.037. Epub 2016 Jun 11. — View Citation

Han MK, Arteaga-Solis E, Blenis J, Bourjeily G, Clegg DJ, DeMeo D, Duffy J, Gaston B, Heller NM, Hemnes A, Henske EP, Jain R, Lahm T, Lancaster LH, Lee J, Legato MJ, McKee S, Mehra R, Morris A, Prakash YS, Stampfli MR, Gopal-Srivastava R, Laposky AD, Punturieri A, Reineck L, Tigno X, Clayton J. Female Sex and Gender in Lung/Sleep Health and Disease. Increased Understanding of Basic Biological, Pathophysiological, and Behavioral Mechanisms Leading to Better Health for Female Patients with Lung Disease. Am J Respir Crit Care Med. 2018 Oct 1;198(7):850-858. doi: 10.1164/rccm.201801-0168WS. — View Citation

Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999 Jan;159(1):179-87. doi: 10.1164/ajrccm.159.1.9712108. — View Citation

Hettel D, Zhang A, Alyamani M, Berk M, Sharifi N. AR Signaling in Prostate Cancer Regulates a Feed-Forward Mechanism of Androgen Synthesis by Way of HSD3B1 Upregulation. Endocrinology. 2018 Aug 1;159(8):2884-2890. doi: 10.1210/en.2018-00283. — View Citation

Hunt JF, Fang K, Malik R, Snyder A, Malhotra N, Platts-Mills TA, Gaston B. Endogenous airway acidification. Implications for asthma pathophysiology. Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):694-9. doi: 10.1164/ajrccm.161.3.9911005. — View Citation

Jollin L, Thomasson R, Le Panse B, Baillot A, Vibarel-Rebot N, Lecoq AM, Amiot V, De Ceaurriz J, Collomp K. Saliva DHEA and cortisol responses following short-term corticosteroid intake. Eur J Clin Invest. 2010 Feb;40(2):183-6. doi: 10.1111/j.1365-2362.2009.02219.x. Epub 2009 Oct 29. — View Citation

Lahm T, Albrecht M, Fisher AJ, Selej M, Patel NG, Brown JA, Justice MJ, Brown MB, Van Demark M, Trulock KM, Dieudonne D, Reddy JG, Presson RG, Petrache I. 17beta-Estradiol attenuates hypoxic pulmonary hypertension via estrogen receptor-mediated effects. Am J Respir Crit Care Med. 2012 May 1;185(9):965-80. doi: 10.1164/rccm.201107-1293OC. Epub 2012 Mar 1. — View Citation

Marozkina N, Zein J, DeBoer MD, Logan L, Veri L, Ross K, Gaston B. Dehydroepiandrosterone Supplementation May Benefit Women with Asthma Who Have Low Androgen Levels: A Pilot Study. Pulm Ther. 2019 Dec;5(2):213-220. doi: 10.1007/s41030-019-00101-9. Epub 2019 Oct 21. — View Citation

National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol. 2007 Nov;120(5 Suppl):S94-138. doi: 10.1016/j.jaci.2007.09.043. Erratum In: J Allergy Clin Immunol. 2008 Jun;121(6):1330. — View Citation

Phipatanakul W, Mauger DT, Sorkness RL, Gaffin JM, Holguin F, Woodruff PG, Ly NP, Bacharier LB, Bhakta NR, Moore WC, Bleecker ER, Hastie AT, Meyers DA, Castro M, Fahy JV, Fitzpatrick AM, Gaston BM, Jarjour NN, Levy BD, Peters SP, Teague WG, Fajt M, Wenzel SE, Erzurum SC, Israel E; Severe Asthma Research Program. Effects of Age and Disease Severity on Systemic Corticosteroid Responses in Asthma. Am J Respir Crit Care Med. 2017 Jun 1;195(11):1439-1448. doi: 10.1164/rccm.201607-1453OC. Erratum In: Am J Respir Crit Care Med. 2018 Apr 1;197(7):970-971. — View Citation

Sadatsafavi M, Lynd L, Marra C, Carleton B, Tan WC, Sullivan S, Fitzgerald JM. Direct health care costs associated with asthma in British Columbia. Can Respir J. 2010 Mar-Apr;17(2):74-80. doi: 10.1155/2010/361071. — View Citation

Watson AC, Rosenfield RL, Fang VS. Recovery from glucocorticoid inhibition of the responses to corticotrophin-releasing hormone. Clin Endocrinol (Oxf). 1988 May;28(5):471-7. doi: 10.1111/j.1365-2265.1988.tb03681.x. — View Citation

Zein J, Gaston B, Bazeley P, DeBoer MD, Igo RP Jr, Bleecker ER, Meyers D, Comhair S, Marozkina NV, Cotton C, Patel M, Alyamani M, Xu W, Busse WW, Calhoun WJ, Ortega V, Hawkins GA, Castro M, Chung KF, Fahy JV, Fitzpatrick AM, Israel E, Jarjour NN, Levy B, Mauger DT, Moore WC, Noel P, Peters SP, Teague WG, Wenzel SE, Erzurum SC, Sharifi N. HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma. Proc Natl Acad Sci U S A. 2020 Jan 28;117(4):2187-2193. doi: 10.1073/pnas.1918819117. Epub 2020 Jan 13. — View Citation

Zein JG, Erzurum SC. Asthma is Different in Women. Curr Allergy Asthma Rep. 2015 Jun;15(6):28. doi: 10.1007/s11882-015-0528-y. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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