Evaluer farmakokinetik og sikkerhed ved DHEA med langsom frigivelse (DHEA)
12. august 2026 opdateret af: Kirsten Kloepfer, Indiana University
Fase IIa klinisk forsøg til evaluering af farmakokinetik og sikkerhed ved DHEA med langsom frigivelse
Dette er en undersøgelse for at se på farmakokinetiske niveauer af forskellige doser af langsom frigivelse DHEA hos personer med svær astma.
Studieoversigt
Detaljeret beskrivelse
Farmakokinetiske (PK) undersøgelser af DHEA i astma generelt, og svær astma i særdeleshed, er aldrig blevet udført.
I mange sygdomme adskiller PK sig fra patienter med sygdom fra kontrolpersoner og dem med andre tilstande.
Derfor undersøger forskere, om PK-niveauer af DHEA med langsom frigivelse er forskellige hos personer med svær astma, som har HSD3B1 AA- eller AC-fænotyperne
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
18
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Indiana
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Indianapolis, Indiana, Forenede Stater, 46202
- Riley Hospital for Children
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Indianapolis, Indiana, Forenede Stater, 46202
- University Hospital
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 50 år (Voksen)
Tager imod sunde frivillige
Ingen
Beskrivelse
Inklusionskriterier:
- Voksen mand eller kvinde i alderen mellem 18 og 50 på tidspunktet for tilmelding
- Beviser for astma påvist ved enten bronkodilatator-reversibilitet eller methacholin-respons enten under indkøring eller ved historisk bevis for begge kriterier, hvis test blev udført i henhold til enten 2017 ERS-tekniske standard eller 1999 ATS-retningslinjerne eller eksterne undersøgelser, forudsat at komplette flowsæt volumen loops er blevet gennemgået og godkendt af PI. Disse kriterier er defineret som et af følgende: stigning i FEV1 mindre end eller lig med 12 procent og 200 ml efter op til 8 pust albuterol; positiv methacholin defineret som PC20 større end eller lig med 16 mg/ml, eller PD20 større end eller lig med 400 mcg; dokumenteret lægediagnose af svær astma i henhold til NHLBI-retningslinjer; Konsekvent brug af en ICS/LABA-inhalator i de foregående 2 måneder; Ikke ryger; hunner må ikke være gravide eller ammende; fravær af ikke-allergiske komorbiditeter; baseline DHEA-S-koncentration < 45 μg/dL hos kvinder og < 90 μg/dL hos mænd; genotype testet positiv for enten HSD3B1 AA eller AC specifik variant
Ekskluderingskriterier:
- Gravid eller aktivt forsøger at blive gravid; amning
- positiv uringraviditetstest
- Kendt anden lungesygdom end astma
- Akut (ikke astma-relateret) dyspnø, viral luftvejssygdom eller astmaforværring inden for 4 uger efter screening
- Systemisk glukokortikoiddosering til vedligeholdelse >10 mg/dag af prednison eller tilsvarende
- Patienter med signifikante ikke-allergiske komorbiditeter (f. cerebral parese, hjertesygdom, nyresygdom, leversygdom osv.)
- Patienter med nogen kendt central eller perifer endokrin abnormitet såsom tidlig pubertet eller diabetes
- Patienter med en kendt tidligere bivirkning over for DHEA
- Aktuel ryger- eller pakkeårshistorie > 5 år (inkluderer vaping-/nikotininhalationsanordninger)
- Positiv urin cotinin test (> 100 mg/ml)
- Brug af prednison eller antibiotika inden for de sidste 4 uger
- Brug af præstationsfremmende lægemidler inden for de sidste 2 uger
- Brug af DHEA inden for de sidste 2 uger
- Androgen brug af enhver grund
- HSD3B1 CC fænotype
- Enhver anden tilstand eller konstatering, der ville kompromittere forsøgspersonens sikkerhed eller kvaliteten af undersøgelsesdataene eller på anden måde forstyrre opnåelsen af undersøgelsens mål, som bestemt af PI
- Menopausal amenoré af historie
- Positiv PSA (>4 ng/ml) (prostataspecifikt antigen)
- Patienter i biologisk behandling for astma
- Forudgående diagnose af stemmebåndsdysfunktion, bronkopulmonal dysplasi, cystisk fibrose, kronisk obstruktiv lungesygdom eller anden lungesygdom
- Systolisk blodtryk > 150 mm Hg og/eller diastolisk blodtryk > 90 mm Hg
- Hjertefrekvenser uden for intervallet 50 til 120 slag i minuttet eller med en patologisk uregelmæssighed
- Patienter, der lider af yderligere akut eller kronisk patologi, som efter screeningslægens mening gør dem uegnede til undersøgelse eller øger de risici, der er forbundet med undersøgelsen.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Andet: Slow Release DHEA
This is a single-arm, sequential study.
The single arm will start with a one-time 50mg dose visit followed by a washout period.
Next is a 100mg dose visit followed by a washout.
Next is a twice daily 50mg dosing for 3 days, every 12 hours, followed by a washout.
Finally, this is followed by a twice daily 100mg dosing for 3 days, every 12 hours, followed by a washout.
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.
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DHEA er et hormon, der produceres af kroppens binyrer.
I lægemiddelform er det tilgængeligt som et håndkøbstilskud, der er tilgængeligt på markedet uden recept.
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Number of Participants With a Peak DHEA Concentration ≥100ng/mL or < 100ng/mL at Any Time Point During Single or Multiple Dose Treatments.
Tidsramme: Outcome measure assessed at 50mg Single Dose Visit (Day 14), 100mg Single Dose Visit (Day 22), 50mg Multiple Dose Treatment (Days 30-32), 100mg Multiple Dose Treatment (Days 40-42)
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The objective is to determine the maximum tolerated dose of slow release DHEA in patients with asthma and AA or AC genotype by measuring the presence in and difference of pharmacokinetics of DHEA in the blood at two dose levels (50mg and 100mg).
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Outcome measure assessed at 50mg Single Dose Visit (Day 14), 100mg Single Dose Visit (Day 22), 50mg Multiple Dose Treatment (Days 30-32), 100mg Multiple Dose Treatment (Days 40-42)
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Number of Participants With a Significant, Sustained Increase in DHEA-S in Blood Levels and Without a Significant, Sustained Increased in DHEA-S in Blood Levels for More Than 24hrs, During Multiple Dose Treatments.
Tidsramme: Outcome measure assessed every 24 hours during 50mg Multiple Dose Treatment (Days 30-32) and every 24 hours during 100mg Multiple Dose Treatment (Days 40-42)
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The objective is to determine the maximum tolerated dose of slow release DHEA in patients with asthma and AA or AC genotype by measuring the presence in and difference of pharmacokinetics of DHEA-S in the blood at two dose levels (50mg and 100mg).
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Outcome measure assessed every 24 hours during 50mg Multiple Dose Treatment (Days 30-32) and every 24 hours during 100mg Multiple Dose Treatment (Days 40-42)
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Number of Participants With Adverse Events (AEs) Related to Study, Unlikely Related to Study, or no AEs at All, at Any Time Point During Single Dose Periods, Multiple Dose Periods, or Washout Periods.
Tidsramme: From administration of the first dose to 12 hours after the final dose (up to 59 days)
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The objective is to determine the maximum tolerated dose of slow release DHEA in patients with asthma and AA or AC genotype by evaluating the occurrences and severity of adverse events during or after dosing at two levels (5omg and 100mg).
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From administration of the first dose to 12 hours after the final dose (up to 59 days)
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Number of Participants With Significant Change in Vital Sign Measurement and no Significant Change in Vital Sign Measurements After 50mg Single Dose and After 100mg Single Dose.
Tidsramme: Outcome measure assessed at 50mg Single Dose Visit (Day 14) and 100mg Single Dose Visit (Day 22).
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The objective is to evaluate the safety and tolerability of slow release DHEA in asthma by measuring the change in vital signs from before 50mg single dose treatment to after 50mg single dose treatment and from beginning of 100mg dose treatment to after 100mg dose treatment.
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Outcome measure assessed at 50mg Single Dose Visit (Day 14) and 100mg Single Dose Visit (Day 22).
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Number of Participants With Significant Change in Asthmatic Symptoms, or no Significant Change in Asthmatic Symptoms, After 50mg Multiple Dose and 100mg Multiple Dose.
Tidsramme: Outcome measure assessed at 50mg Multiple Dose Treatment (Day 30), 100mg Multiple Dose Treatment (Day 40)
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The objective is to evaluate the safety and tolerability of slow release DHEA in asthma by measuring the change in physical symptoms from before treatment to after treatment.
Physical symptoms will include reports such as cough, shortness of breath, chest tightness, wheeze, as measured by symptom diary record.
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Outcome measure assessed at 50mg Multiple Dose Treatment (Day 30), 100mg Multiple Dose Treatment (Day 40)
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Number of Participants With a Decrease in FEV1, an Increase in FEV1, and no Change in FEV1, After 50mg Multiple Dose Treatments and 100mg Multiple Dose Treatments.
Tidsramme: Outcome measure assessed from beginning to end of 50mg Multiple Dose Treatment (Days 30-32), and beginning to end of 100mg Multiple Dose Treatment (Days 40-42)
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The objective is to evaluate the safety and tolerability of slow release DHEA in asthma patients by performing pulmonary function testing to obtain measurements of FEV (forced expiratory volume) before treatment and after treatment.
All subjects completed the treatment, but not all subjects participated in the pulmonary function testing.
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Outcome measure assessed from beginning to end of 50mg Multiple Dose Treatment (Days 30-32), and beginning to end of 100mg Multiple Dose Treatment (Days 40-42)
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Number of Participants That Experienced an Asthma Exacerbation and That Did Not Experience an Asthma Exacerbation During or After 50mg Single Dose, 100mg Single Dose, 50mg Multiple Dose Treatment, 100mg Multiple Dose Treatment.
Tidsramme: Outcome measure assessed at 50mg Single Dose Visit (Day 14), 100mg Single Dose Visit (Day 22), 50mg Multiple Dose Treatment (Days 30-32), 100mg Multiple Dose Treatment (Days 40-42).
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The objective is to evaluate the safety and tolerability of slow release DHEA in asthma patients by recording any instance of asthma exacerbation event during or after treatment.
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Outcome measure assessed at 50mg Single Dose Visit (Day 14), 100mg Single Dose Visit (Day 22), 50mg Multiple Dose Treatment (Days 30-32), 100mg Multiple Dose Treatment (Days 40-42).
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Samarbejdspartnere
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
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- 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.
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- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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- 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.
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- 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.
- 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.
- 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.
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Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
3. marts 2023
Primær færdiggørelse (Faktiske)
24. april 2025
Studieafslutning (Faktiske)
24. april 2025
Datoer for studieregistrering
Først indsendt
14. november 2022
Først indsendt, der opfyldte QC-kriterier
14. november 2022
Først opslået (Faktiske)
21. november 2022
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
2. september 2026
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
12. august 2026
Sidst verificeret
1. august 2026
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 15038
- P01HL158507 (U.S. NIH-bevilling/kontrakt)
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Ja
Studerer et amerikansk FDA-reguleret enhedsprodukt
Ingen
produkt fremstillet i og eksporteret fra U.S.A.
Ingen
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