PHYSICAL ACTIVITY AND FVIII CLEARANCE: RELEVANCE FOR PERSONALIZED THERAPY IN SEVERE HAEMOPHILIA A (PHYSEMO)

NCT04303936 | Unknown FDA Device

• 1 other identifier: 2364
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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.

  12 months

• 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.

  12 months

• Physical activity (mean number of daily steps) level and HJHS score

  12 months

• Physical activity, measured by mean number of daily steps, andHaem-A-QoL score

  12 months

Study Arms (1)

Patients with severe HA under FVIII concentrates prophylaxis

OTHER

Device: SenseWear® armband device

Interventions

SenseWear® armband device DEVICE

Metabolic Holter, Physical Activity and Lifestyle, Portable outpatient "multi-sensor" energy consumption in calories (EE), movement, physical activity, quality of life, sleep

Patients with severe HA under FVIII concentrates prophylaxis

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Catholic University of the Sacred Heart: lead

Study Sites (1)

Fondazione Policlinico Universitario Agostino Gemelli, IRCCS

Rome, 00168, Italy

RECRUITING

Related Publications (17)

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  PMID: 19452402 BACKGROUND

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• 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.

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• Arranz P, Remor E, Quintana M, Villar A, Diaz JL, Moreno M, Monteagudo J, Ugarriza A, Soto I, Perez R, Chacon J, Garcia-Luaces M, Cid A, Balda I, Lopez MF, Gutierrez MJ, Martinez E, Marrero C, Prieto M, Sedano C, Vaca R, Altisent C, Hernandez-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. doi: 10.1111/j.1365-2516.2004.00918.x.

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• 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.

  PMID: 27862662 BACKGROUND

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 16, 2020
• First Posted: March 11, 2020
• Study Start: January 9, 2020
• Primary Completion: December 30, 2020
• Study Completion: December 30, 2020
• Last Updated: March 11, 2020

Record last verified: 2020-03

Locations

IT (1)