Study of Individuals Affected With Hypoplasminogenemia

NCT ID: NCT03797495

Last Updated: 2025-08-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-12-18

Study Completion Date

2027-04-19

Brief Summary

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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

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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.

Conditions

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Plasminogen Deficiency

Study Design

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Observational Model Type

COHORT

Study Time Perspective

OTHER

Eligibility Criteria

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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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondazione Angelo Bianchi Bonomi

OTHER

Sponsor Role collaborator

Indiana Hemophilia &Thrombosis Center, Inc.

OTHER

Sponsor Role lead

Responsible Party

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Amy D Shapiro, MD

Medical Director

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Amy D Shapiro, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana Hemophilia &Thrombosis Center, Inc.

Flora Peyvandi, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Univeristy of Milan

Locations

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The University of Alabama (UAB)

Birmingham, Alabama, United States

Site Status RECRUITING

Rush University Medical Center

Chicago, Illinois, United States

Site Status RECRUITING

Indiana Hemophila @Thrombosis Center

Indianapolis, Indiana, United States

Site Status RECRUITING

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

Minneapolis, Minnesota, United States

Site Status RECRUITING

Stony Brook University | Stony Brook Medicine

East Setauket, New York, United States

Site Status RECRUITING

SUNY Upstate Medical University, Pediatric Hematology/Oncology

Syracuse, New York, United States

Site Status RECRUITING

Wake Forest University

Winston-Salem, North Carolina, United States

Site Status RECRUITING

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Vanderbilt Children's Hematology-Oncology

Nashville, Tennessee, United States

Site Status COMPLETED

Cook Children's Medical Center

Forth Worth, Texas, United States

Site Status RECRUITING

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status COMPLETED

Seattle Children's Hospital

Seattle, Washington, United States

Site Status RECRUITING

Hospital Britanico Buenos Aires

Buenos Aires, , Argentina

Site Status RECRUITING

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

Melbourne, Victoria, Australia

Site Status RECRUITING

Children's Health Queensland Hospital and Health Service

South Brisbane, , Australia

Site Status RECRUITING

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

Innsbruck, , Austria

Site Status RECRUITING

Windsor Regional Hospital

Windsor, Ontario, Canada

Site Status RECRUITING

CHU Sainte-Justine

Montreal, Quebec, Canada

Site Status RECRUITING

CHU de Québec Université Laval

Québec, Quebec, Canada

Site Status RECRUITING

University of Saskatchewan

Saskatoon, , Canada

Site Status RECRUITING

Alexandra Hospital, Athens, Hematology Department

Athens, , Greece

Site Status RECRUITING

Safra's Children Hospital, Sheba Medical Center

Tel Aviv, , Israel

Site Status RECRUITING

Angelo Bianchi Bonomi Hemophilia and Thrombosis Center,

Milan, , Italy

Site Status RECRUITING

University Hospital of Padova

Padua, , Italy

Site Status RECRUITING

Faculty of Medicine, Chiang Mai University

Chiang Mai, , Thailand

Site Status RECRUITING

Dokuz Eylul University pediatric Pulmonology, Allergy and Clinical Immunology

Izmir, Balçova, Turkey (Türkiye)

Site Status ACTIVE_NOT_RECRUITING

Istanbul Üniversitesi Onkoloji Enstitüsü

Istanbul, , Turkey (Türkiye)

Site Status RECRUITING

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

Istanbul, , Turkey (Türkiye)

Site Status ACTIVE_NOT_RECRUITING

Yuzuncu Yil University Faculty of Medicine Department of Ophthalmology

Van, , Turkey (Türkiye)

Site Status RECRUITING

Royal Free Hospital, Royal Free London NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Argentina Australia Austria Canada Greece Israel Italy Thailand Turkey (Türkiye) United Kingdom

Central Contacts

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Amy D Shapiro, MD

Role: CONTACT

317-871-0000

Charles Nakar, MD

Role: CONTACT

317-871-0000

Facility Contacts

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Lisa Beatty, RN

Role: primary

205-638-2394

Sharon Davis

Role: backup

Mindy Simpson, MD

Role: primary

312-942-3034

Brian Jenkins

Role: backup

312-563-1883

Neelam Thukral, CCRC

Role: primary

317-871-0000 ext. 373

Charles Nakar, MD

Role: backup

317-871-0000

Sharon Hwee

Role: primary

Kris Beatrez

Role: backup

612.624.1928

Nicole Muhlbauer, MD

Role: primary

(631) 444-9016

Jessica Mannetta

Role: backup

516-329-7843

Karen Bilynsky, RN

Role: primary

315-464-7601

Andrea Dvorak, MD

Role: backup

315 464 5294

Madeline G Hicks

Role: primary

336-713-3553

Joia Johnson

Role: backup

336-713-3553

Frederico Xavier, MD

Role: primary

412-209-7411

Debbie Vehec

Role: backup

412-209-7564

Heather Urbanek

Role: primary

682-885-1244

Marcela Torres, MD

Role: backup

682 885 4007

Gavin Roach, MD

Role: primary

206-884-1018

Shana Tang

Role: backup

206-884-1268

Jhon A Avila, MD

Role: primary

549 114 187 9723

Jose M Ceresetto, MD

Role: backup

541 143 041 081

Paul Monagle, MD

Role: primary

61 3 9936-6330

Jodi Hislop, RN

Role: backup

61 3 9936-6330

Ruby Gander

Role: primary

61 7 3068 4142

Trang Le

Role: backup

61 7 3069 7206

Lukas Hackl, MD

Role: primary

+43-512-504-83144

Erica Figgins, MSc

Role: primary

519-254-5577 ext. 52300

Batul Khumushi, CCRP

Role: backup

519 254 5577 ext. 52899

Valerie Arsenault, MD

Role: primary

(514) 345-4931 ext. 3757

Bianka Courcelle

Role: backup

514-345-4931 ext. 3757

Marie-Claude Pelland-Marcotte, MD

Role: primary

14185254444 ext. 79029

Stéphanie Cyr

Role: backup

418 525-4444 ext. 40121

Sarah Tehseen, MBBS, MSc. FRCPC

Role: primary

639 998 3972

Rashmi Nagaraj

Role: backup

306-978-8306

Vasiliki Gkalea, MD

Role: primary

0030 (690) 682-2189

Charis Matsouka

Role: backup

302132162165

Tami Barazani-Brutman, MD

Role: primary

972 522427949

Sarina Levy, MD

Role: backup

972 547299251

Marzia Menegatti, PhD

Role: primary

+39 - 02/50320727

Maria Teresa Sartori, MD

Role: primary

3334530450

C. Dalla Porta, MD

Role: backup

39 049 821 1111

Rungrote Natesirinilkul, MD

Role: primary

66 2 201 1749

Basak Koc, MD

Role: primary

90 5326003027

Muhammed Batur, MD

Role: primary

904 322 150 473 ext. 6030

Amy O'Reilly

Role: primary

0207 794 0500

Joanna Calvert

Role: backup

020 3758 2000

References

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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.

Reference Type BACKGROUND
PMID: 1455395 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17900274 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25208887 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 27629020 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29321155 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32001536 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40403316 (View on PubMed)

Other Identifiers

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HISTORY

Identifier Type: -

Identifier Source: org_study_id

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