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

• ClinicalTrials.gov Identifier: NCT04845555
• Recruitment Status: Recruiting
• First Posted: April 15, 2021
• Last Update Posted: April 15, 2021
• Sponsor: Prof. Dr. Dr. Thomas Hilberg
• Collaborators: Takeda; University of Bonn
• Information provided by (Responsible Party): Prof. Dr. Dr. Thomas Hilberg, University of Wuppertal

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment
Hemophilia A	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 Design

• Study Type: Observational
• Estimated Enrollment: 30 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Association Between Individual Clotting Factor Level Monitoring and the Risk of Bleeding Whilst Physical Active Conditions
• Actual Study Start Date: September 1, 2019
• Estimated Primary Completion Date: December 1, 2021
• Estimated Study Completion Date: December 30, 2021

Groups and Cohorts

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.

Outcome Measures

Primary Outcome Measures :

1. Type of physical activity documented in a digital template [ Time Frame: 12 months ]
   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
2. Physiological parameters (heart rate of PwH, measured with FitBit Charge 4 HR) [ Time Frame: 12 months ]
   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.
3. Total annual bleeding rate [ Time Frame: 12 months ]
   Number of bleedings per year, documented in a digital template
4. Clotting factor VIII level [ Time Frame: 12 months ]
   In percent, documented in "myPKFIT"

Secondary Outcome Measures :

1. Factor substitution in international units [ Time Frame: 12 months ]
   Administered international units of factor VIII
2. Frequency of factor substitution [ Time Frame: 12 months ]
   Frequency and units of factor replacement
3. Score of subjective quality of life measured by the SF36 Health Survey [ Time Frame: Baseline, after 6 and 12 months ]
   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
4. Joint status in score points measured by Hemophilia Joint Health Score [ Time Frame: Baseline, after 6 and 12 months ]
   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
5. Pain status measured by the German Pain Questionnaire [ Time Frame: Baseline, after 6 and 12 months ]
   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
6. Pressure pain thresholds [ Time Frame: Baseline, after 6 and 12 months ]
   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.
7. Score of subjective physical performance measured by the HEP-Test-Q [ Time Frame: Baseline, after 6 and 12 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

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

Criteria

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)

Contacts and Locations

Contacts

Contact: Thomas Hilberg, Prof.; 0202-373-208-12; hilberg@uni-wuppertal.de

Locations

Germany

Department of Sports Medicine, University of Wuppertal; Recruiting

Wuppertal, North Rhine-Westphalia, Germany, 42117

Contact: Thomas Hilberg, Prof. 004920237320812 sportmedizin@uni-wuppertal.de

Sponsors and Collaborators

Prof. Dr. Dr. Thomas Hilberg

Takeda

University of Bonn

Investigators

• Study Chair: Thomas Hilberg, Prof.; Head of Department of sports medicine Wuppertal

More Information

• Responsible Party: Prof. Dr. Dr. Thomas Hilberg, Prof. Dr. med. Dr. phil., University of Wuppertal
• ClinicalTrials.gov Identifier: NCT04845555
• Other Study ID Numbers: 002286
• First Posted: April 15, 2021
• Last Update Posted: April 15, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Prof. Dr. Dr. Thomas Hilberg, University of Wuppertal:

Hemophilia A; Clotting Factor Level; Exercise; Pharmacokinetics; Physical activity

Additional relevant MeSH terms:

Hemophilia A; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn