Study of Individuals Affected With Hypoplasminogenemia

NCT03797495 | Recruiting DMC

• 1 other identifier: HISTORY
• Study Type: observational
• Target: 100
• Locations: 10 countries
• Sites: 28

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

Conditions

Plasminogen Deficiency

Outcome Measures

Primary Outcomes (3)

• Define the natural history of plasminogen deficiency

  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

  2 years

• Identify factors that contribute to or correlate with disease expression and severity

  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

  5 years

• Create a specimen biobank

  Bank plasma, serum and DNA on consenting enrolled subjects

  15 years

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Study population will include males and females affected with hyposplasminogenemia of any age and their first degree family members (siblings and parents).

You may qualify if:

• Signed informed consent and assent as applicable (Appendix 1)
• 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)
• All ages included
• Available clinical history and treatment for at least 1 year prior to entry except for infants \< 1 year of age
• Willingness to provide samples for analysis including DNA, plasma etc.
• Willingness to participate in prospective follow-up for up to 3 years

You may not qualify if:

• Previous organ transplant recipient
• 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
• Refuses to provide informed consent
• Special patient populations, including prisoners or, are deemed medically or cognitively unsuitable for research by their treating physician
• Inability to obtain a blood sample due to poor or limited venous access

Sponsors & Collaborators

• Indiana Hemophilia &Thrombosis Center, Inc.: lead
• Fondazione Angelo Bianchi Bonomi: collaborator

Study Sites (30)

The University of Alabama (UAB)

Birmingham, Alabama, 35233, United States

RECRUITING

Rush University Medical Center

Chicago, Illinois, 60612, United States

RECRUITING

Indiana Hemophila @Thrombosis Center

Indianapolis, Indiana, 46260, United States

RECRUITING

University of Minnesota, Pediatric Hem/Onc & Cancer Survivorship Program

Minneapolis, Minnesota, 55455, United States

RECRUITING

Stony Brook University | Stony Brook Medicine

East Setauket, New York, 11733, United States

RECRUITING

SUNY Upstate Medical University, Pediatric Hematology/Oncology

Syracuse, New York, 13210, United States

RECRUITING

Wake Forest University

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Vanderbilt Children's Hematology-Oncology

Nashville, Tennessee, 37232, United States

COMPLETED

Cook Children's Medical Center

Forth Worth, Texas, 76104, United States

RECRUITING

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

COMPLETED

Seattle Children's Hospital

Seattle, Washington, 98105-3901, United States

RECRUITING

Hospital Britanico Buenos Aires

Buenos Aires, C1280, Argentina

RECRUITING

Murdoch Children's Research Institute, The Royal Children's Hospital

Melbourne, Victoria, 3052, Australia

RECRUITING

Children's Health Queensland Hospital and Health Service

South Brisbane, QLD 4101, Australia

RECRUITING

Medical University of Innsbruck, University Clinic for Pediatrics and Adolescent Medicine

Innsbruck, A-6020, Austria

RECRUITING

Windsor Regional Hospital

Windsor, Ontario, N8W 1L9, Canada

RECRUITING

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

RECRUITING

CHU de Québec Université Laval

Québec, Quebec, A0121, Canada

RECRUITING

University of Saskatchewan

Saskatoon, SK S7N 0W8, Canada

RECRUITING

Alexandra Hospital, Athens, Hematology Department

Athens, 11528, Greece

RECRUITING

Safra's Children Hospital, Sheba Medical Center

Tel Aviv, Israel

RECRUITING

Angelo Bianchi Bonomi Hemophilia and Thrombosis Center,

Milan, 20122, Italy

RECRUITING

University Hospital of Padova

Padua, 35100, Italy

RECRUITING

Faculty of Medicine, Chiang Mai University

Chiang Mai, 50200, Thailand

RECRUITING

Dokuz Eylul University pediatric Pulmonology, Allergy and Clinical Immunology

Izmir, Balçova, 35330, Turkey (Türkiye)

ACTIVE NOT RECRUITING

Istanbul Üniversitesi Onkoloji Enstitüsü

Istanbul, 34093, Turkey (Türkiye)

RECRUITING

Istanbul University Cerrahpsasa, Cerrahpsasa Medical Faculty Pediatric Hematology and Oncology Department

Istanbul, 34098, Turkey (Türkiye)

ACTIVE NOT RECRUITING

Yuzuncu Yil University Faculty of Medicine Department of Ophthalmology

Van, 65040, Turkey (Türkiye)

RECRUITING

Royal Free Hospital, Royal Free London NHS Foundation Trust

London, United Kingdom

RECRUITING

Related Publications (7)

• Tait RC, Walker ID, Conkie JA, Islam SI, McCall F, Mitchell R, Davidson JF. Plasminogen levels in healthy volunteers--influence of age, sex, smoking and oral contraceptives. Thromb Haemost. 1992 Nov 10;68(5):506-10.

  PMID: 1455395 BACKGROUND

• Schuster V, Hugle B, Tefs K. Plasminogen deficiency. J Thromb Haemost. 2007 Dec;5(12):2315-22. doi: 10.1111/j.1538-7836.2007.02776.x. Epub 2007 Sep 26.

  PMID: 17900274 BACKGROUND

• Ma Q, Ozel AB, Ramdas S, McGee B, Khoriaty R, Siemieniak D, Li HD, Guan Y, Brody LC, Mills JL, Molloy AM, Ginsburg D, Li JZ, Desch KC. Genetic variants in PLG, LPA, and SIGLEC 14 as well as smoking contribute to plasma plasminogen levels. Blood. 2014 Nov 13;124(20):3155-64. doi: 10.1182/blood-2014-03-560086. Epub 2014 Sep 10.

  PMID: 25208887 BACKGROUND

• Celkan T. Plasminogen deficiency. J Thromb Thrombolysis. 2017 Jan;43(1):132-138. doi: 10.1007/s11239-016-1416-6.

  PMID: 27629020 BACKGROUND

• Shapiro AD, Nakar C, Parker JM, Albert GR, Moran JE, Thibaudeau K, Thukral N, Hardesty BM, Laurin P, Sandset PM. Plasminogen replacement therapy for the treatment of children and adults with congenital plasminogen deficiency. Blood. 2018 Mar 22;131(12):1301-1310. doi: 10.1182/blood-2017-09-806729. Epub 2018 Jan 10.

  PMID: 29321155 BACKGROUND

• Shapiro AD, Menegatti M, Palla R, Boscarino M, Roberson C, Lanzi P, Bowen J, Nakar C, Janson IA, Peyvandi F. An international registry of patients with plasminogen deficiency (HISTORY). Haematologica. 2020 Mar;105(3):554-561. doi: 10.3324/haematol.2019.241158. Epub 2020 Jan 30.

  PMID: 32001536 BACKGROUND

• Sang Y, Menegatti M, Brody JA, Wiggins KL, Cooley BC, Kapfer KN, Kangro K, de Laat B, Peyvandi F, Flick MJ, Smith NL, Shapiro AD, Wolberg AS. Plasminogen activation and plasmin activity are not necessary to prevent venous thrombosis/thromboembolism. Blood. 2025 Sep 11;146(11):1346-1358. doi: 10.1182/blood.2025028680.

  PMID: 40403316 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum, and plasma will be retained. Time perspective is retrospective and prospective.

MeSH Terms

Conditions

Congenital Plasminogen Deficiency

Study Officials

• Amy D Shapiro, MD

  Indiana Hemophilia &Thrombosis Center, Inc.

  PRINCIPAL INVESTIGATOR

• Flora Peyvandi, MD, PhD

  Univeristy of Milan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy D Shapiro, MD

CONTACT

317-871-0000; ashapiro@ihtc.org

Charles Nakar, MD

CONTACT

317-871-0000; cnakar@ihtc.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director

Study Record Dates

• First Submitted: December 28, 2018
• First Posted: January 9, 2019
• Study Start: December 18, 2018
• Primary Completion (Estimated): March 8, 2027
• Study Completion (Estimated): April 19, 2027
• Last Updated: August 28, 2025

Record last verified: 2024-10

Locations

AU (1); TU (4); IT (2); AR (1); GB (1); IL (1); TH (1); CA (4); GR (1); US (12)