Association Between Individual Clotting Factor Level Monitoring and the Risk of Bleeding Whilst Physical Active Conditions (AIM-Active)

The aim of this prospective multicentre study is to evaluate the influence of individual clotting factor level while being physically active

Study Overview

• Status: Recruiting
• Conditions: Hemophilia A
• Intervention / Treatment: Other: Observation of the association between clotting factor level and risk of bleeding whilst physical activity

Detailed Description

In patients with haemophilia (PwH) repetitive joint bleedings result in a so called haemophilic arthropathy, which is often associated with chronic pain as well as functional restrictions.

Due to the opportunity of sufficient factor treatment regimes, physical activity is no longer considered as a risk factor for PwH. In contrast, the large amount of current scientific evidence demonstrated high benefits of regular exercising for PwH. Meanwhile, physical activity is integrated as recommendation in the ´Guidelines for the management of hemophilia´. Nevertheless, the detailed influence of the exact course of the individual clotting factor level corresponding to the intensity of physical activities in consideration of possible bleeding events in adult PwH have not been examined to date.

The aim of this prospective multicentre study is to evaluate the influence of individual clotting factor level while being physically activie. Hereby the focus is on haemophilic specific parameters such as bleeding events, factor treatment and pain. On the basis of this study, an individualized clotting factor level should be determined which ensures a minimized risk of a bleeding event, considering type and intensity of the exercises. In line with these new findings, further interventional studies could be initiated in order to safely enhance the degraded physical performance as well as quality of life in PwH.

The generated knowledge could be further used in the development of haemophilic specific recommendations regarding physical activity in consideration of the individual clotting factor level.

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

• Study Contact: Name: Thomas Hilberg, Prof.; Phone Number: 0202-373-208-12; Email: hilberg@uni-wuppertal.de

Study Locations

• Germany
  • North Rhine-Westphalia
    • Wuppertal, North Rhine-Westphalia, Germany, 42117
      • Recruiting
      • Department of Sports Medicine, University of Wuppertal
      • Contact: Thomas Hilberg, Prof.; Phone Number: 004920237320812; Email: sportmedizin@uni-wuppertal.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients suffering from hemophilia A recruited by cooperating hemophilic treatment centers.

Description

Inclusion Criteria:

• patients suffering from moderate or severe hemophilia A (FVIII <5%, ≥ 12 years old)
• factor treatment with ADVATE© or ADYNOVI©
• use of myPKFiT

Exclusion Criteria:

• patients suffering from other coagulopathies
• participants without written consent
• participants < 12 years old
• joint surgery like arthroscopy, synovectomy up to six months before study
• suffering from different rheumatologic diseases like M. Bechterew, Psoriasi or other local or generalized joint infections (Borreliosis, septic arthritis)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with hemophilia A; Patients suffering from moderate or severe hemophilia A (FVIII <5%) over the age of 12 years.

Other: Observation of the association between clotting factor level and risk of bleeding whilst physical activity; The participants of this study will be monitored for a period of twelve months regarding individual clotting factor level, bleeding episodes as well as type and intensity of physical activity. By doing so, bleeding events, factor consumption as well as the course of the individual factor clotting factor level will be documented via the mobile application "myPKFiT". This individual factor treatment regime will be compared with the retrospective treatment outcome in the last twelve months before the first study visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type of physical activity documented in a digital template	PwH are used to document the type and intensity of their physical activity in terms of a digital template which will be electronically requested monthly by co-workers of this study	12 months
Physiological parameters (heart rate of PwH, measured with FitBit Charge 4 HR)	Individual type and intensity of physical activity measured as heart rate by an electronic activity wristband (Fitbit charge 4 HR, synchronized in corresponding FitBit Application) For the final evaluation, each physical activity will be clustered regarding type and intensity to differ between the specific demands of activity.	12 months
Total annual bleeding rate	Number of bleedings per year, documented in a digital template	12 months
Clotting factor VIII level	In percent, documented in "myPKFIT"	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Factor substitution in international units	Administered international units of factor VIII	12 months
Frequency of factor substitution	Frequency and units of factor replacement	12 months
Score of subjective quality of life measured by the SF36 Health Survey	Questionnaire: The possible score ranges from 0 to 100 points. 0 points represent the greatest possible restriction of health, while 100 points represent the absence of health restrictions	Baseline, after 6 and 12 months
Joint status in score points measured by Hemophilia Joint Health Score	The clinical joint situation will be examined in all PwH and controls by the Haemophilia Joint Health Score, which assesses, e.g., swelling, muscle atrophy, crepitus on motion, axial deformity and range of motion. Higher score points imply an increased deficit in the functional and structural joint status as a sign of more pronounced haemophilic arthropathy, with a maximum possible value of 26 score points for knee and ankle joints and a maximum of 20 score points for elbow joints	Baseline, after 6 and 12 months
Pain status measured by the German Pain Questionnaire	Questionnaire includes: Demographic data (age, sex, body weight, height); detailed subjective description of pain (localization, characteristics, time course, intensity, etc.); assessment of pain-relieving and pain-enhancing conditions, subjective pain perception (the pain description list SBL); pain-related impairment (also valid for Von Korff grading); subjective pain model, causal attribution, relieving or enhancing factors; screening of depressive and anxiety disorders (Depression, Anxiety and Stress Scale, DASS). Screening of depressive and anxious disorders (Depression, Anxiety and Stress Scale, DASS); General well-being (Marburg Questionnaire on Habitual Well-being, MFHW); Course of disease (extent of previous treatment, physicians consulted for pain, use of medication, pain therapy treatment procedures, operations); Medical and psychological/psychiatric comorbidity	Baseline, after 6 and 12 months
Pressure pain thresholds	Pressure pain thresholds will be examined by using a digital algometer device (FPX 25 Compact Digital Algom-eter, Wagner Instruments, Greenwich, CT, USA) with a robe area of 1 cm2. Pressure is increased by a rate of 10 Newton/second. It is a measuring method to analyze the current pain condition. Participants are instructed to report the moment when the stimulus becomes painful for the first time. The maximum pressure is 140 N to avoid tissue damages. The mean value of three measurements will be used as pressure pain thresholds for further statistical analyses. Pressure pain thresholds of knee, ankle, elbow, sternum and forehead (the last two being the reference points) will be examined.	Baseline, after 6 and 12 months
Score of subjective physical performance measured by the HEP-Test-Q	Questionnaire of subjective physical functioning for patients with hemophilia.The HEP Test-Q consists of 25 items belonging to 4 dimensions 'flexibility', 'strength & coordination', 'endurance' and 'body perception' and a single item that measures changes in physical functioning compared to the previous year. Subscales and total score are transformed to a 0-100 scale, with high scores representing better physical functioning.	Baseline, after 6 and 12 months

Collaborators and Investigators

• Sponsor: Prof. Dr. Dr. Thomas Hilberg
• Collaborators: Takeda; University of Bonn
• Investigators: Study Chair: Thomas Hilberg, Prof., Head of Department of sports medicine Wuppertal

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: July 28, 2020
• First Submitted That Met QC Criteria: April 13, 2021
• First Posted (Actual): April 15, 2021

Study Record Updates

• Last Update Posted (Actual): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Exercise; Pharmacokinetics; Physical activity; Hemophilia A; Clotting Factor Level
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: 002286

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No