A Prospective Assessment of Bone Health in Patients With Severe Hemophilia A on Factor VIII vs Factor Mimetic Prophylaxis (Efa Emi Bone Health Study)
2026年6月3日 更新者：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.
調査の概要
状態
まだ募集していません
条件
詳細な説明
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.
研究の種類
観察的
入学 (推定)
50
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Carol D Pierce, RN
- 電話番号：501-364-4440
- メール：piercecarold@uams.edu
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
健康ボランティアの受け入れ
いいえ
サンプリング方法
非確率サンプル
調査対象母集団
Patients that are seen at dedicated Hemophilia treatment Centers
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
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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.
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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.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Longitudinal change in femoral neck bone mineral density (g/cm²)
時間枠：Baseline and annually through 5 years.
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Bone mineral densitometry
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Baseline and annually through 5 years.
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Longitudinal change in Lumbar spine (L1-L4) bone mineral density (g/cm²)
時間枠：Baseline and annually through 5 years.
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Bone mineral densitometry
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Baseline and annually through 5 years.
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Longitudinal change in total hip bone mineral density (g/cm²)
時間枠：Baseline and annually through 5 years.
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Bone mineral densitometry
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Baseline and annually through 5 years.
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Longitudinal Change in Bone Remodeling Biomarkers and Cytokines
時間枠：Baseline and annually through 5 years.
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PINP, CTX-I, OPG, RANKL, IL-1β, IL-6, and TNF-α
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Baseline and annually through 5 years.
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Change in Thrombin Generation and Plasmin Generation Parameters
時間枠：Baseline and annually through 5 years
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Simultaneous Thrombin and Plasmin Generation Assay
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Baseline and annually through 5 years
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者：Divyaswathi Citla Sridhar, MD、Arkansas Children's Reserach Institute
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年7月1日
一次修了 (推定)
2031年8月1日
研究の完了 (推定)
2032年8月1日
試験登録日
最初に提出
2026年5月6日
QC基準を満たした最初の提出物
2026年5月6日
最初の投稿 (実際)
2026年5月12日
学習記録の更新
投稿された最後の更新 (実際)
2026年6月4日
QC基準を満たした最後の更新が送信されました
2026年6月3日
最終確認日
2026年6月1日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 300130
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
いいえ
IPD プランの説明
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
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