Endothelial Colony-Forming Cells in Patients With VWD, AVWS and Healthy Subjects

NCT07358013 | Recruiting

• 1 other identifier: 3387 n.6569
• Study Type: observational
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to learn how endothelial colony-forming cells (ECFCs) behave in people with von Willebrand disease (VWD), acquired von Willebrand syndrome (AVWS), and in healthy individuals.

Conditions

Von Willebrand Disease (VWD); Acquired Von Willebrand Disease

Keywords

von Willebrand disease; von Willebrand factor; ex vivo; endothelial colony forming cells (ECFCs)

Outcome Measures

Primary Outcomes (1)

• ECFCs isolation and characterization

  Assessment of differences between ECFCs derived from patients with VWD or AVWS and healthy controls. Basal and stimulated VWF production and secretion by ECFCs, including basal VWF levels in culture media and cell lysates and stimulated VWF release following exposure to biological or chemical compounds, measured by ELISA (IU/dL) and compared between patients with VWD/AVWS and healthy controls. VWF mRNA expression levels in ECFCs, assessed by quantitative real-time PCR and expressed as ΔΔCt, compared between patients with VWD/AVWS and healthy controls.

  42 weeks from enrollment start

Secondary Outcomes (3)

• Correlation of ECFC VWF Antigen Protein and mRNA Levels with Plasma and Platelet VWF Antigen/Activity Levels and Molecular Defect.

  42 weeks from enrollment start

• Comparison of angiogenic properties of ECFCs from patients with VWD/AVWS and healthy controls

  42 weeks from enrollment start

• Evaluation of Allele-Specific siRNA to Restore Normal VWF Levels in Type 2A VWD

  42 weeks from enrollment start

Study Arms (2)

von willebrand disease/ Acquired von Willebrand disease patients

Patients with a confirmed diagnosis of VWD or AVWS. Participants will undergo peripheral blood sample collection for plasma VWF measurements and ECFCs isolation and characterization. In patients with VWD without prior molecular characterization, an additional blood sample will be collected for genetic analysis.

Diagnostic Test: Blood sample collection for VWF measurements in plasma; Other: Blood sample collection for ECFC isolation and characterization; Other: Genetic testing of VWF

Healthy donors

Healthy volunteers with no personal or family history of bleeding or thrombotic disorders, serving as the reference population for the study. Participants will undergo peripheral blood sample collection plasma VWF measurements and ECFCs isolation and characterization.

Diagnostic Test: Blood sample collection for VWF measurements in plasma; Other: Blood sample collection for ECFC isolation and characterization

Interventions

Blood sample collection for ECFC isolation and characterization OTHER

Blood samples will be collected to isolate ECFCs and perform their subsequent characterization.

Healthy donors; von willebrand disease/ Acquired von Willebrand disease patients

Genetic testing of VWF OTHER

An additional blood sample will be collected for VWF genetic testing in patients with VWD without prior molecular characterization.

von willebrand disease/ Acquired von Willebrand disease patients

Blood sample collection for VWF measurements in plasma DIAGNOSTIC_TEST

Plasma samples will be collected for the measurement of VWF levels.

Healthy donors; von willebrand disease/ Acquired von Willebrand disease patients

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study will include the enrollment of subjects with a previous diagnosis of VWD or AVWS and a group of healthy volunteers (controls). Patients will be selected among those referred at Angelo Bianchi Bonomi Haemophilia and Thrombosis Center, with a previous diagnosis of VWD or AVWS. Healthy volunteers, defined as individuals without a previous diagnosis of bleeding or thrombotic disorders will be enrolled in equal number to cases with the aim of creating a ECFCs reference group. At enrollment, controls will undergo an interview to confirm their health status, they will be asked to sign the informed consent and then they will undergo a blood withdrawal necessary to confirm plasma VWF levels and to isolate ECFCs as already described for patients.

You may qualify if:

• Patients with von Willebrand disease (VWD) or acquired von Willebrand syndrome (AVWS)
• Age ≥ 16 years.
• Previous diagnosis of von Willebrand disease or acquired von Willebrand syndrome, defined as one of the following:
• Group A - Type 1 VWD:
• VWF levels ≤ 30 IU/dL, regardless of bleeding history, or
• VWF levels ≤ 0.50 IU/mL in the presence of abnormal bleeding.
• Group B - Congenital or acquired VWD (VWD or AVWS):
• Diagnosis of congenital or acquired VWD, with or without gastrointestinal bleeding.
• Group C - Subgroup study (Type 2A VWD):
• One patient with type 2A VWD selected for a dedicated sub-study involving allele-specific siRNA silencing of the mutant allele.
• Ability and willingness to provide written informed consent.
• For patients without prior molecular characterization: willingness to undergo VWF gene sequencing and to sign the related informed consent.
• No prior diagnosis of VWD, bleeding disorders, or thrombotic disorders.
• Willingness to donate blood for study procedures.
• Ability and willingness to provide written informed consent.

You may not qualify if:

• Pregnancy.
• Anemia, as determined at screening or based on medical history.

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead

Study Sites (1)

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, A.B.Bonomi Hemophilia and Thrombosis Center

Milan, 20122, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

* Plasma samples for VWF testing (all enrolled subjects). * Peripheral blood-derived ECFCs, cryopreserved after successful isolation (all enrolled subjects). * Blood sample for VWF genetic analysis (patients without prior molecular characterization).

MeSH Terms

Conditions

von Willebrand Diseases

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Flora Peyvandi, MD, PhD

CONTACT

02-55035414; flora.peyvandi@policlinico.mi.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2025
• First Posted: January 22, 2026
• Study Start: November 11, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): May 31, 2028
• Last Updated: January 22, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)