Synovial Proliferation on Routine Ultrasound: Active or Inactive?

NCT06809972 | Recruiting

• 1 other identifier: 2BEGIN
• Study Type: observational
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

There is cumulating evidence for the presence of non-observed or subclinical joint bleeding in patients with haemophilia. Early detection of active subclinical synovial proliferation would allow early intervention in order to prevent deterioration of joint health. Patients with subclinical (=non-observed) signs of synovial proliferation in knee(s), ankle(s) and/or elbow(s) will be invited to participate in this study to further characterize the synovial proliferation status (active or inactive) by means of physical examination, MRI, ultrasound and elastography. Synovial proliferation status will be monitored for a maximum period of 12 weeks, during which participants will also receive standard-of-care treatment, i.e. administration of optimized coagulation factor replacement therapy and prescription of the NSAID celecoxib (optional).

Conditions

Haemophilia; Hemophilia A; Hemophilia B

Keywords

Subclinical synovial proliferation; Ultrasound; MRI; Elastography

Outcome Measures

Primary Outcomes (1)

• - The primary objective of this study is to evaluate the diagnostic accuracy of physical examination and ultrasound to identify active synovial proliferation in haemophilia patients with subclinical synovial hypertrophy.

  As no gold standard to identify active subclinical proliferation is available, "change in synovial proliferation over time" will be used as surrogate endpoint. This is measured by ultrasound assessment according HEAD-US protocol . Possible outcomes are: no change (baseline HEAD-US score = 12-week follow-up HEAD-US score) or changed (baseline HEAD-US score \< or \> 12-week follow-up HEAD-US score). Fully recovered synovial proliferation will also be categorized as changed. The diagnostic accuracy will be derived comparing 'change in synovial proliferation' with the 'presumed' definition at baseline (active or inactive). Definition of active synovial proliferation at baseline: synovial proliferation on ultrasound and the presence of at least one of the following criteria: * HJHS swelling \>0 * Warmth palpation absent/present at baseline * JADE Synovial Hyperaemia \>0 * No history of synovial proliferation (yes/no) * Hemosiderin on MRI (IPSG\>0) * Elastography

  12 weeks

Secondary Outcomes (3)

• - To identify predictors for (changes in) synovial proliferation status within participant characteristics (age, baseline treatment, joint bleeding history) and joint characteristics (extent of arthropathy (Pettersson score on X-rays)).

  12 weeks

• - To evaluate the diagnostic accuracy of the presence of synovial hemosiderin, as measured by MRI, to identify active synovial proliferation in haemophilia patients with subclinical synovial hypertrophy.

  12 weeks

• - To evaluate the diagnostic accuracy of synovial elastography to identify active synovial proliferation in hemophilia patients with subclinical synovial hypertrophy

  12 weeks

Other Outcomes (1)

• - To describe elastographic differences between active clinical synovitis, active subclinical synovial hypertrophy and inactive subclinical hypertrophy.

  At baseline (week 0) without follow-up

Interventions

Ultrasound imaging OTHER

Ultrasound, MRI and elastography to screen for and follow subclinical synovial changes in ankle, elbow and knee.

Also known as: MRI, Elastography

Eligibility Criteria

• Age: 12 Years+
• Gender Eligibility Details: Haemophilia is an X-linked disease.
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of male participants ≥ 12 years of age, with severe haemophilia A or B treated with prophylaxis, who were diagnosed with asymptomatic synovial proliferation in ≥1 joint (ankle, knee and/or elbow) by means of ultrasound imaging during routine screening at the outpatient clinic of the Van Creveldkliniek, UMC Utrecht, the Netherlands.

You may qualify if:

• Gender: male
• Patients with severe haemophilia A or B
• Treated with registered prophylaxis medication including coagulation factors and by- passing agents.
• Age ≥ 12 years
• Subclinical synovial proliferation in ≥1 joint (ankle, knee and/or elbow), defined as the presence of hypertrophic synovium, score \>0 according to the HEAD-US protocol, as confirmed during routine ultrasound screening.
• Able to give written informed consent.

You may not qualify if:

• On demand therapy.
• Currently treated with any type of haemophilia prophylaxis medication.
• Joints with prosthesis or treated with arthrodesis will not be included for physical examination and ultrasound analysis. However, participants may still be included in the study with their other joints.
• Confirmed inflammatory joint diseases such as rheumatoid arthritis or psoriatic arthritis.
• History of inhibitor development (≥ 5 Bethesda Units\* (BU) at any time or 1-5 BU for
• Contra-indication for treatment with NSAIDs, (allergy, severe liver failure, renal failure (GFR \<30ml/min), congestive heart failure (NYHA II-IV), peripheral arterial disease and/or cerebrovascular disease.

Sponsors & Collaborators

• Van Creveldkliniek: lead

Study Sites (1)

University Medical Center Utrecht

Utrecht, 3584CX, Netherlands

RECRUITING

MeSH Terms

Conditions

Hemophilia A; Hemophilia B

Interventions

High-Energy Shock Waves

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; Genetic Diseases, X-Linked

Intervention Hierarchy (Ancestors)

Ultrasonic Waves; Sound; Radiation, Nonionizing; Radiation; Physical Phenomena

Study Officials

• Lize van Vulpen, MD, PhD

  University Medical Center Utrecht - Van Creveldkliniek

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lize van Vulpen, MD, PhD

CONTACT

+31887558450; l.f.d.vanvulpen-2@umcutrecht.nl

Merel Timmer, PhD

CONTACT

m.a.timmer@umcutrecht.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: October 30, 2024
• First Posted: February 5, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: 15 years after study closure.
• Access Criteria: Please contact the principal investigator, Dr. L.F.D. van Vulpen.

Locations

NL (1)