A Prospective Assessment of Bone Health in Patients With Severe Hemophilia A on Factor VIII vs Factor Mimetic Prophylaxis (Efa Emi Bone Health Study)
3. juni 2026 oppdatert av: Divyaswathi Citla Sridhar, Arkansas Children's Hospital Research Institute
A Multi-institution Prospective Assessment of Bone Health in Patients With Severe Hemophilia A on Factor VIII vs Factor Mimetic Prophylaxis (Efa Emi Bone Health Study)
This study will compare bone mineral density in patients with severe hemophilia A receiving prophylaxis with emicizumab or efanesoctocog alfa.
Participants will undergo assessments of bone mineral density, bone remodeling biomarkers, thrombin generation, plasmin generation, and joint health over a five-year period.
The study aims to evaluate whether differences in prophylactic therapy are associated with differences in bone health outcomes.
Studieoversikt
Status
Har ikke rekruttert ennå
Forhold
Detaljert beskrivelse
Reduced bone mineral density, osteoporosis, and fractures are increasingly recognized in persons with severe hemophilia A. The mechanisms underlying impaired bone health in hemophilia are multifactorial and may include reduced physical activity, chronic joint disease, inflammation, and abnormalities in coagulation-related pathways involved in bone remodeling.
Thrombin has been shown to play an important role in bone metabolism through activation of protease-activated receptor-1 (PAR-1) signaling pathways that influence osteoblast and osteoclast activity. Reduced thrombin generation in severe hemophilia A may contribute to decreased bone formation and increased bone resorption.
Efanesoctocog alfa is an extended half-life factor VIII replacement therapy that maintains higher circulating factor VIII levels and supports thrombin generation. Emicizumab is a non-factor prophylactic therapy that effectively prevents bleeding but does not replace factor VIII. The comparative effects of these therapies on long term bone health have not been well established.
This prospective observational study will compare longitudinal changes in bone mineral density among patients with severe hemophilia A receiving prophylaxis with emicizumab or efanesoctocog alfa over 5 years. Participants will undergo serial dual-energy X-ray absorptiometry (DXA) assessments and evaluation of bone remodeling biomarkers, inflammatory cytokines, thrombin generation, plasmin generation, and joint health over a five-year period.
Studietype
Observasjonsmessig
Registrering (Antatt)
50
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiekontakt
- Navn: Carol D Pierce, RN
- Telefonnummer: 501-364-4440
- E-post: piercecarold@uams.edu
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
Tar imot friske frivillige
Nei
Prøvetakingsmetode
Ikke-sannsynlighetsprøve
Studiepopulasjon
Patients that are seen at dedicated Hemophilia treatment Centers
Beskrivelse
Inclusion Criteria:
- The participant or legally authorized representative is willing and able to provide written informed consent.
- Diagnosis of severe hemophilia A (factor VIII activity < 1%).
- Male sex.
- Age between 30 and 50 years (inclusive).
- BMI between 18.5 and 40 kg/m2
- The participant must have been on prophylaxis with Efanesoctocog alfa or Emicizumab for at least 3 months prior to enrollment and intend to remain on the current regimen for the next 5 years.
- Willingness to undergo all research procedures, including DEXA scans and the collection of blood samples.
- Willingness to complete all standard-of-care bleeding and treatment logs.
Exclusion Criteria:
- Unwillingness of the participant, parent, or legally authorized representative to provide informed consent.
- Diagnosis of a bleeding disorder other than or in addition to severe hemophilia A.
- Active Factor VIII inhibitors at the time of enrollment
- History of a disease known to influence bone metabolism unrelated to a bleeding disorder. (Examples: Paget's disease, osteogenesis imperfecta, Ehlers Danlos syndrome, Hyperparathyroidism)
- Past or present treatment with any anti-osteoporotic medication, excluding oral vitamin D or oral calcium supplements.
- Documented HIV infection or HCV infection (whether in progress or cured) at the cirrhotic stage.
- Presence of a non-removable metal device that would interfere with research procedures.
- Inability to tolerate a DEXA scan due to limited range of motion or body habitus.
- History of bone fractures or surgical repair within 8 weeks prior to enrollment.
- Participants with weight >300 pounds, due to limitations of DEXA scanner
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
Kohorter og intervensjoner
Gruppe / Kohort |
|---|
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Patients with Severe Hemophilia A on Efanesoctocog alfa prophylaxis
Participants with severe hemophilia A receiving prophylaxis with efanesoctocog alfa as part of routine clinical care.
Participants will undergo longitudinal assessments of bone mineral density, bone remodeling biomarkers, thrombin generation, plasmin generation, and joint health over a five-year period.
|
|
Patients with Severe Hemophilia A on Emicizumab prophylaxis
Participants with severe hemophilia A receiving prophylaxis with emicizumab as part of routine clinical care.
Participants will undergo longitudinal assessments of bone mineral density, bone remodeling biomarkers, thrombin generation, plasmin generation, and joint health over a five-year period.
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Longitudinal change in femoral neck bone mineral density (g/cm²)
Tidsramme: Baseline and annually through 5 years.
|
Bone mineral densitometry
|
Baseline and annually through 5 years.
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Longitudinal change in Lumbar spine (L1-L4) bone mineral density (g/cm²)
Tidsramme: Baseline and annually through 5 years.
|
Bone mineral densitometry
|
Baseline and annually through 5 years.
|
|
Longitudinal change in total hip bone mineral density (g/cm²)
Tidsramme: Baseline and annually through 5 years.
|
Bone mineral densitometry
|
Baseline and annually through 5 years.
|
|
Longitudinal Change in Bone Remodeling Biomarkers and Cytokines
Tidsramme: Baseline and annually through 5 years.
|
PINP, CTX-I, OPG, RANKL, IL-1β, IL-6, and TNF-α
|
Baseline and annually through 5 years.
|
|
Change in Thrombin Generation and Plasmin Generation Parameters
Tidsramme: Baseline and annually through 5 years
|
Simultaneous Thrombin and Plasmin Generation Assay
|
Baseline and annually through 5 years
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Divyaswathi Citla Sridhar, MD, Arkansas Children's Reserach Institute
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- Paschou SA, Anagnostis P, Karras S, Annweiler C, Vakalopoulou S, Garipidou V, Goulis DG. Bone mineral density in men and children with haemophilia A and B: a systematic review and meta-analysis. Osteoporos Int. 2014 Oct;25(10):2399-407. doi: 10.1007/s00198-014-2773-7. Epub 2014 Jul 8.
- Sivagurunathan S, Pagel CN, Loh LH, Wijeyewickrema LC, Pike RN, Mackie EJ. Thrombin inhibits osteoclast differentiation through a non-proteolytic mechanism. J Mol Endocrinol. 2013 Apr 23;50(3):347-59. doi: 10.1530/JME-12-0177. Print 2013 Jun.
- Song SJ, Pagel CN, Campbell TM, Pike RN, Mackie EJ. The role of protease-activated receptor-1 in bone healing. Am J Pathol. 2005 Mar;166(3):857-68. doi: 10.1016/S0002-9440(10)62306-1.
- Pagel CN, Song SJ, Loh LH, Tudor EM, Murray-Rust TA, Pike RN, Mackie EJ. Thrombin-stimulated growth factor and cytokine expression in osteoblasts is mediated by protease-activated receptor-1 and prostanoids. Bone. 2009 May;44(5):813-21. doi: 10.1016/j.bone.2008.12.031. Epub 2009 Jan 15.
- Pagel CN, de Niese MR, Abraham LA, Chinni C, Song SJ, Pike RN, Mackie EJ. Inhibition of osteoblast apoptosis by thrombin. Bone. 2003 Oct;33(4):733-43. doi: 10.1016/s8756-3282(03)00209-6.
- Al Dieri R, de Laat B, Hemker HC. Thrombin generation: what have we learned? Blood Rev. 2012 Sep;26(5):197-203. doi: 10.1016/j.blre.2012.06.001. Epub 2012 Jul 2.
- Goldscheitter G, Recht M, Sochacki P, Manco-Johnson M, Taylor JA. Biomarkers of bone disease in persons with haemophilia. Haemophilia. 2021 Jan;27(1):149-155. doi: 10.1111/hae.13986. Epub 2020 Aug 27.
- Gerstner G, Damiano ML, Tom A, Worman C, Schultz W, Recht M, Stopeck AT. Prevalence and risk factors associated with decreased bone mineral density in patients with haemophilia. Haemophilia. 2009 Mar;15(2):559-65. doi: 10.1111/j.1365-2516.2008.01963.x. Epub 2009 Feb 1.
- Wallny TA, Scholz DT, Oldenburg J, Nicolay C, Ezziddin S, Pennekamp PH, Stoffel-Wagner B, Kraft CN. Osteoporosis in haemophilia - an underestimated comorbidity? Haemophilia. 2007 Jan;13(1):79-84. doi: 10.1111/j.1365-2516.2006.01405.x.
- Ghosh K, Shetty S. Bone health in persons with haemophilia: a review. Eur J Haematol. 2012 Aug;89(2):95-102. doi: 10.1111/j.1600-0609.2012.01803.x. Epub 2012 Jun 22.
- Walker IR, Julian JA. Causes of death in Canadians with haemophilia 1980-1995. Association of Hemophilia Clinic Directors of Canada. Haemophilia. 1998 Sep;4(5):714-20. doi: 10.1046/j.1365-2516.1998.00179.x.
- Smit C, Rosendaal FR, Varekamp I, Brocker-Vriends A, Van Dijck H, Suurmeijer TP, Briet E. Physical condition, longevity, and social performance of Dutch haemophiliacs, 1972-85. BMJ. 1989 Jan 28;298(6668):235-8. doi: 10.1136/bmj.298.6668.235.
- Bunta AD. It is time for everyone to own the bone. Osteoporos Int. 2011 Aug;22 Suppl 3:477-82. doi: 10.1007/s00198-011-1704-0. Epub 2011 Aug 17.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Antatt)
1. juli 2026
Primær fullføring (Antatt)
1. august 2031
Studiet fullført (Antatt)
1. august 2032
Datoer for studieregistrering
Først innsendt
6. mai 2026
Først innsendt som oppfylte QC-kriteriene
6. mai 2026
Først lagt ut (Faktiske)
12. mai 2026
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
4. juni 2026
Siste oppdatering sendt inn som oppfylte QC-kriteriene
3. juni 2026
Sist bekreftet
1. juni 2026
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 300130
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
NEI
IPD-planbeskrivelse
Individual participant data will not be shared with with other researchers , and each participating site has access to only their centers data; however , aggregated data will be included in future publications and will be made available toparticipating centers following study completion
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
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