- ICH GCP
- Реестр клинических исследований США
- Клиническое испытание NCT07582276
A Prospective Assessment of Bone Health in Patients With Severe Hemophilia A on Factor VIII vs Factor Mimetic Prophylaxis (Efa Emi Bone Health Study)
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)
Обзор исследования
Статус
Условия
Подробное описание
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.
Тип исследования
Регистрация (Оцененный)
Контакты и местонахождение
Контакты исследования
- Имя: Carol D Pierce, RN
- Номер телефона: 501-364-4440
- Электронная почта: piercecarold@uams.edu
Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
- Взрослый
Принимает здоровых добровольцев
Метод выборки
Исследуемая популяция
Описание
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
Учебный план
Как устроено исследование?
Детали дизайна
Когорты и вмешательства
Группа / когорта |
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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.
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Longitudinal change in femoral neck bone mineral density (g/cm²)
Временное ограничение: 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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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Longitudinal change in Lumbar spine (L1-L4) bone mineral density (g/cm²)
Временное ограничение: 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)
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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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Соавторы и исследователи
Соавторы
Следователи
- Главный следователь: Divyaswathi Citla Sridhar, MD, Arkansas Children's Reserach Institute
Публикации и полезные ссылки
Общие публикации
- 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.
Даты записи исследования
Изучение основных дат
Начало исследования (Оцененный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
- Генетические заболевания, врожденные
- Гематологические заболевания
- Нарушения свертывания крови
- Геморрагические расстройства
- Нарушения свертывания крови, наследственные
- Нарушения белковой коагуляции
- Врожденные, наследственные и неонатальные заболевания и аномалии
- Гемики и лимфатические заболевания
- Гемофилия А
Другие идентификационные номера исследования
- 300130
Планирование данных отдельных участников (IPD)
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Описание плана IPD
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .