Hemophilia A Clinical Trial
— PHYSEMOOfficial title:
PHYSICAL ACTIVITY AND FVIII CLEARANCE: RELEVANCE FOR PERSONALIZED THERAPY IN SEVERE HAEMOPHILIA A
NCT number | NCT04303936 |
Other study ID # | 2364 |
Secondary ID | |
Status | Recruiting |
Phase | N/A |
First received | |
Last updated | |
Start date | January 9, 2020 |
Est. completion date | December 30, 2020 |
Verified date | March 2020 |
Source | Catholic University of the Sacred Heart |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
In persons with severe haemophilia A (HA) infused factor VIII (FVIII) half-life and other
pharmacokinetic parameters can vary according to determinants such as blood group, von
Willebrand factor (VWF) level or age. However, FVIII pharmacokinetics (PK) has not been
thoroughly studied in patients with severe HA as a function of daily physical activity.
Patients with severe HA (FVIII <1%) are predisposed to prolonged bleeding following even
minimal musculoskeletal injuries. Potential consequences of repeated musculoskeletal bleeding
are pain, arthropathy and physical disability. The key standard of care for HA patients is
prophylactic infusions of FVIII concentrates (25-50 IU kg-1 infused 2-3 x/week), depending on
individual response.
The level of infused FVIII decreases as a function of time according to both specific PK
features of each product and biochemical/genetic characteristics of the patients or different
clinical conditions.
Some critical points remain still unraveled, for instance, whether or not FVIII AUC is
significantly affected by physical activity/exercise, in response to increased metabolic rate
or subclinical/microhaemorrhages in patients with severe HA.
It is known that vigorous-intensity physical activity/exercise can transiently but
significantly increase circulating levels of endogenous VWF and consequently FVIII in normal
subjects and in patients with moderate or mild haemophilia A. The proposed study is a Proof
of Concept one as it will be aimed at investigating the relation between daily physical
activity, measured by SenseWear® armband device, as number of daily steps, and PK variability
of infused rec-FVIII concentrate. This kind of investigation has never been done and it is a
great interest also for the evaluation of patients' quality of life.
Status | Recruiting |
Enrollment | 20 |
Est. completion date | December 30, 2020 |
Est. primary completion date | December 30, 2020 |
Accepts healthy volunteers | No |
Gender | Male |
Age group | 12 Years to 60 Years |
Eligibility |
Inclusion Criteria: - Patients (12-60 yr. old) with severe HA under FVIII concentrates prophylaxis will be selected at the Haemostasis and Thrombosis Center of the Fondazione Policlinico Universitario "A. Gemelli", IRCCS, Rome, Italy (FPG) and at the satellite site at the Department of Cellular Biotechnology and Haemathology, Policlinico Umberto I, Sapienza University of Rome, Italy (UNSA_SS). Exclusion Criteria: - All patients with malignant tumors, or treated with anticoagulant / antiplatelet agents, and suffering from other congenital coagulation disorders (von disease Willebrand disease, other congenital deficiency of coagulation factors) or severe thrombocytopenia (<30,000 Plt /µL). Patients who would have undergone a severe bleed or surgery during the past 3 months before enrolment. |
Country | Name | City | State |
---|---|---|---|
Italy | Fondazione Policlinico Universitario Agostino Gemelli, IRCCS | Rome |
Lead Sponsor | Collaborator |
---|---|
Catholic University of the Sacred Heart |
Italy,
Arranz P, Remor E, Quintana M, Villar A, Díaz JL, Moreno M, Monteagudo J, Ugarriza A, Soto I, Pérez R, Chacón J, García-Luaces M, Cid A, Balda I, López MF, Gutíerrez MJ, Martínez E, Marrero C, Prieto M, Sedano C, Vaca R, Altisent C, Hernández-Navarro F; Hemofilia-QoL Group. Development of a new disease-specific quality-of-life questionnaire to adults living with haemophilia. Haemophilia. 2004 Jul;10(4):376-82. — View Citation
Blanchette VS, Shapiro AD, Liesner RJ, Hernández Navarro F, Warrier I, Schroth PC, Spotts G, Ewenstein BM; rAHF-PFM Clinical Study Group. Plasma and albumin-free recombinant factor VIII: pharmacokinetics, efficacy and safety in previously treated pediatric patients. J Thromb Haemost. 2008 Aug;6(8):1319-26. doi: 10.1111/j.1538-7836.2008.03032.x. Epub 2008 May 22. — View Citation
Chang CY, Li TY, Cheng SN, Pan RY, Wang HJ, Lin SY, Chen YC. Prevalence and severity by age and other clinical correlates of haemophilic arthropathy of the elbow, knee and ankle among Taiwanese patients with haemophilia. Haemophilia. 2017 Mar;23(2):284-291. doi: 10.1111/hae.13117. Epub 2016 Nov 8. — View Citation
Collins PW, Björkman S, Fischer K, Blanchette V, Oh M, Schroth P, Fritsch S, Casey K, Spotts G, Ewenstein BM. Factor VIII requirement to maintain a target plasma level in the prophylactic treatment of severe hemophilia A: influences of variance in pharmacokinetics and treatment regimens. J Thromb Haemost. 2010 Feb;8(2):269-75. doi: 10.1111/j.1538-7836.2009.03703.x. Epub 2009 Nov 23. — View Citation
Groen WG, den Uijl IE, van der Net J, Grobbee DE, de Groot PG, Fischer K. Protected by nature? Effects of strenuous physical exercise on FVIII activity in moderate and mild haemophilia A patients: a pilot study. Haemophilia. 2013 Jul;19(4):519-23. doi: 10.1111/hae.12111. Epub 2013 Mar 19. — View Citation
Hoots WK, Rodriguez N, Boggio L, Valentino LA. Pathogenesis of haemophilic synovitis: clinical aspects. Haemophilia. 2007 Nov;13 Suppl 3:4-9. — View Citation
Kepa S, Horvath B, Reitter-Pfoertner S, Schemper M, Quehenberger P, Grundbichler M, Heistinger M, Neumeister P, Mannhalter C, Pabinger I. Parameters influencing FVIII pharmacokinetics in patients with severe and moderate haemophilia A. Haemophilia. 2015 May;21(3):343-50. doi: 10.1111/hae.12592. Epub 2015 Jan 13. — View Citation
Lafeber FP, Miossec P, Valentino LA. Physiopathology of haemophilic arthropathy. Haemophilia. 2008 Jul;14 Suppl 4:3-9. doi: 10.1111/j.1365-2516.2008.01732.x. Review. — View Citation
Lalezari S, Martinowitz U, Windyga J, Enriquez MM, Delesen H, Schwartz L, Scharrer I. Correlation between endogenous VWF:Ag and PK parameters and bleeding frequency in severe haemophilia A subjects during three-times-weekly prophylaxis with rFVIII-FS. Haemophilia. 2014 Jan;20(1):e15-22. doi: 10.1111/hae.12294. Epub 2013 Nov 20. Erratum in: Haemophilia. 2014 Mar;20(2):e193. — View Citation
Lee IM, Hsieh CC, Paffenbarger RS Jr. Exercise intensity and longevity in men. The Harvard Alumni Health Study. JAMA. 1995 Apr 19;273(15):1179-84. — View Citation
Lippi G, Maffulli N. Biological influence of physical exercise on hemostasis. Semin Thromb Hemost. 2009 Apr;35(3):269-76. doi: 10.1055/s-0029-1222605. Epub 2009 May 18. Review. — View Citation
Macfarlane DJ, Lee CC, Ho EY, Chan KL, Chan D. Convergent validity of six methods to assess physical activity in daily life. J Appl Physiol (1985). 2006 Nov;101(5):1328-34. Epub 2006 Jul 6. — View Citation
Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, Ingram JD, Manco-Johnson ML, Funk S, Jacobson L, Valentino LA, Hoots WK, Buchanan GR, DiMichele D, Recht M, Brown D, Leissinger C, Bleak S, Cohen A, Mathew P, Matsunaga A, Medeiros D, Nugent D, Thomas GA, Thompson AA, McRedmond K, Soucie JM, Austin H, Evatt BL. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007 Aug 9;357(6):535-44. — View Citation
Smith JE. Effects of strenuous exercise on haemostasis. Br J Sports Med. 2003;37(5):433-5. Review. — View Citation
Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, Ludlam CA, Mahlangu JN, Mulder K, Poon MC, Street A; Treatment Guidelines Working Group on Behalf of The World Federation Of Hemophilia. Guidelines for the management of hemophilia. Haemophilia. 2013 Jan;19(1):e1-47. doi: 10.1111/j.1365-2516.2012.02909.x. Epub 2012 Jul 6. — View Citation
van Dijk K, van der Bom JG, Lenting PJ, de Groot PG, Mauser-Bunschoten EP, Roosendaal G, Grobbee DE, van den Berg HM. Factor VIII half-life and clinical phenotype of severe hemophilia A. Haematologica. 2005 Apr;90(4):494-8. — View Citation
Zourikian N, Merlen C, Bonnefoy A, St-Louis J, Rivard GE. Effects of moderate-intensity physical exercise on pharmacokinetics of factor VIII and von Willebrand factor in young adults with severe haemophilia A: a pilot study. Haemophilia. 2016 May;22(3):e177-83. doi: 10.1111/hae.12869. Epub 2016 Mar 14. — View Citation
* Note: There are 17 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Study of the association between physical activity, measured by mean number of daily steps, with the Area Under the Curve (AUC) PK parameter in patients with severe HA under prophylaxis. | Investigate whether and how the daily physical activity (measured as number of steps, using the SenseWear™ Armband device) affects the PK parameter. In more details, the study aims to evaluate whether and how the FVIII AUC PK parameter is significantly associated with the mean number of daily steps in patients with severe HA. | 12 months | |
Secondary | Study of the association between physical activity, measured by the mean number of daily steps, with the clearance (U/ml/hr) of FVIII concentrate PK parameters in patients with severe HA. | Investigate whether and how the daily physical activity (measured as mean number of daily steps, using the SenseWear™ Armband device) affects the PK parameter. In more details, the study aims to evaluate whether and how the FVIII clearance (U/ml/hr) PK parameter is significantly associated with the number of steps in patients with severe HA. | 12 months | |
Secondary | Study of the association between physical activity, measured by the mean number of daily steps, with half life (hr) of FVIII concentrate PK parameters in patients with severe HA. | Investigate whether and how the daily physical activity (measured as mean number of daily steps, using the SenseWear™ Armband device) affects the PK parameter. In more details, the study aims to evaluate whether and how the half life (hr) PK parameter is significantly associated with the number of steps in patients with severe HA. | 12 months | |
Secondary | Physical activity (mean number of daily steps) level and HJHS score | To assess whether and how the physical activity (measured by mean number of daily steps), measured by the SenseWear™ Armband device, is significantly associated with the HJHS score; | 12 months | |
Secondary | Physical activity, measured by mean number of daily steps, andHaem-A-QoL score | To assess whether and how the physical activity, measured by mean number of daily steps) using the SenseWear™ Armband device, is significantly associated with the Haem-A-QoL score. | 12 months |
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