Study of Individuals Affected With Hypoplasminogenemia

Recruiting

• Conditions: Plasminogen Deficiency

• Registration Number: NCT03797495
• Lead Sponsor: Indiana Hemophilia &Thrombosis Center, Inc.

Brief Summary

This is an Investigator initiated retrospective and prospective single cohort study. The study will utilize an international registry and develop a specimen biobank to provide an improved understanding of the natural history of hyposplasminogenemia, to elucidate the heterogeneity of phenotypic expression, identify markers to predict disease course, and inform improved therapeutic modalities

Detailed Description

The aims of this study are to:

1. Define PLGD natural history in a large cohort of individuals with hypoplasminogenemia and their first-degree family members.

2. Identify factors that correlate with disease expression and severity.

3. Create a specimen biobank for further studies, available to other researchers.

The project will be international in scope with two collaborating centers that have created and will collect the subject data and samples. In North/Central/South America, the Indiana Hemophilia \& Thrombosis Center (IHTC) will serve as the primary site while University of Milan will serve as the center for all other sites. The database is housed at the University of Milan, Italy.

Study population will include males and females affected with hyposplasminogenemia of any age. Both one-year retrospective and three-year prospective data will be collected on an international cohort of 100 affected individuals and their first degree family members (parents, siblings; total estimated study population \~500).

Study sample analysis, except for urine analyses, will be centralized and performed in Italy; the plasminogen antibody analysis will be batched for analysis, and the urine analyses will be performed locally. A sample biorepository will be created and ultimately housed in Italy. The study will provide testing for plasminogen activity and antigen, plasminogen genetic analysis, polymorphisms in genes that impact plasminogen expression and fibrinolysis, and global hemostatic assays. In addition, stored samples will be used for further testing and analyses to potentially include whole genome sequencing to further identify plasminogen genetic mutations as needed and to investigate other genetic modifiers of disease expression. An exploratory aim includes investigating the potential relationship with streptococcal strains and altered plasminogen products.

The study period will be 3 years for each enrolled subject. In-person visits will be conducted and samples for analysis will be collected at baseline and at end of study. Interval follow-up will be performed every 6 months by telephone. data will be collected at unscheduled visits that are performed for clinical need at the treating physician's discretion.

Study Timeline

• Study Start: 2018-12-18
• Study First Submitted: 2018-12-28
• Study First Submitted QC: 2019-01-08
• Study First Posted: 2019-01-09
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-30
• Last Update Posted: 2024-11-01
• Primary Completion: 2027-03-08
• Study Completion: 2027-04-19

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Signed informed consent and assent as applicable (Appendix 1)
2. A. Males or females with type 1 PD diagnosed locally with plasminogen activity levels <50% OR B. First degree family members of a person diagnosed with type 1 PD (includes parents, siblings, half-siblings)
3. All ages included
4. Available clinical history and treatment for at least 1 year prior to entry except for infants < 1 year of age
5. Willingness to provide samples for analysis including DNA, plasma etc.
6. Willingness to participate in prospective follow-up for up to 3 years

Exclusion Criteria

1. Previous organ transplant recipient
2. Any psychiatric disorder, other mental disorder, or any other medical disorder that impairs the subject's ability to give informed consent or to comply with the requirements of the study protocol
3. Refuses to provide informed consent
4. Special patient populations, including prisoners or, are deemed medically or cognitively unsuitable for research by their treating physician
5. Inability to obtain a blood sample due to poor or limited venous access

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Create a specimen biobank	15 years	Bank plasma, serum and DNA on consenting enrolled subjects
Define the natural history of plasminogen deficiency	2 years	1. Recruit 100 subjects with hypoplasminogenemia and their first-degree family members; 2. Collect up to 1 year retrospective and 3 year prospective data on symptoms, treatment and interventions
Identify factors that contribute to or correlate with disease expression and severity	5 years	1. Perform centralized plasminogen activity and antigen analyses; 2. Perform centralized genetic analysis to identify changes in the plasminogen gene; 3. Perform centralized analysis of polymorphisms that affect plasminogen activity levels and impact fibrinolysis; 4. Perform local urine analysis; 5. Collect samples to explore the interaction of altered plasminogen proteins with bacterial strains

Trial Locations

Locations (22)

University Hospital of Padova; 🇮🇹 Padua, Italy

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Stony Brook University | Stony Brook Medicine; 🇺🇸 East Setauket, New York, United States

Seattle Children's Hospital; 🇺🇸 Seattle, Washington, United States

Medical University of Innsbruck, University Clinic for Pediatrics and Adolescent Medicine; 🇦🇹 Innsbruck, Austria

CHU Sainte-Justine; 🇨🇦 Montréal, Quebec, Canada

CHU de Québec Université Laval; 🇨🇦 Québec, Canada

Alexandra Hospital, Athens, Hematology Department; 🇬🇷 Athens, Greece

Indiana Hemophila @Thrombosis Center; 🇺🇸 Indianapolis, Indiana, United States

Hemophilia Center of Western Pennsylvania; 🇺🇸 Pittsburgh, Pennsylvania, United States

Vanderbilt Children's Hematology-Oncology; 🇺🇸 Nashville, Tennessee, United States

Cook Children's Medical Center; 🇺🇸 Fort Worth, Texas, United States

The University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States

Hospital Britanico Buenos Aires; 🇦🇷 Buenos Aires, Argentina

Murdoch Children's Research Institute, The Royal Children's Hospital; 🇦🇺 Melbourne, Victoria, Australia

University of Saskatchewan; 🇨🇦 Saskatoon, Canada

Angelo Bianchi Bonomi Hemophilia and Thrombosis Center,; 🇮🇹 Milano, Italy

Faculty of Medicine, Chiang Mai University; 🇹🇭 Chiang Mai, Thailand

Dokuz Eylul University pediatric Pulmonology, Allergy and Clinical Immunology; 🇹🇷 Izmir, Balçova, Turkey

Istanbul Üniversitesi Onkoloji Enstitüsü; 🇹🇷 Istanbul, Turkey

Istanbul University Cerrahpsasa, Cerrahpsasa Medical Faculty Pediatric Hematology and Oncology Department; 🇹🇷 Istanbul, Turkey

Yuzuncu Yil University Faculty of Medicine Department of Ophthalmology; 🇹🇷 Van, Turkey