Study of Individuals Affected With Hypoplasminogenemia (HISTORY)

August 21, 2025 updated by: Amy D Shapiro, MD, Indiana Hemophilia &Thrombosis Center, Inc.

Hypoplasminogenemia: An International RetroSpecTive and PrOspective CohoRt StudY (HISTORY)

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

Study Overview

Status

Recruiting

Conditions

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 Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Charles Nakar, MD
  • Phone Number: 317-871-0000
  • Email: cnakar@ihtc.org

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1280
        • Recruiting
        • Hospital Britanico Buenos Aires
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jose M Ceresetto, MD
        • Sub-Investigator:
          • Jhon A Avila, MD
  • Australia
      • South Brisbane, Australia, QLD 4101
        • Recruiting
        • Children's Health Queensland Hospital and Health Service
        • Contact:
        • Contact:
        • Principal Investigator:
          • Sally Campbell, MD
    • Victoria
      • Melbourne, Victoria, Australia, 3052
        • Recruiting
        • Murdoch Children's Research Institute, The Royal Children's Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Paul Monagle, MD
  • Austria
      • Innsbruck, Austria, A-6020
        • Recruiting
        • Medical University of Innsbruck, University Clinic for Pediatrics and Adolescent Medicine
        • Contact:
        • Principal Investigator:
          • Lukas Hackl, MD
  • Canada
      • Saskatoon, Canada, SK S7N 0W8
    • Ontario
      • Windsor, Ontario, Canada, N8W 1L9
        • Recruiting
        • Windsor Regional Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Andrea Cervi, MD
    • Quebec
  • Greece
      • Athens, Greece, 11528
        • Recruiting
        • Alexandra Hospital, Athens, Hematology Department
        • Contact:
        • Contact:
        • Principal Investigator:
          • Vasiliki Gkalea, MD
  • Israel
  • Italy
      • Milan, Italy, 20122
        • Recruiting
        • Angelo Bianchi Bonomi Hemophilia and Thrombosis Center,
        • Contact:
        • Principal Investigator:
          • Flora Peyvandi, MD,PhD
      • Padua, Italy, 35100
        • Recruiting
        • University Hospital of Padova
        • Contact:
        • Contact:
        • Principal Investigator:
          • Maria Teresa Sartori, MD
  • Thailand
      • Chiang Mai, Thailand, 50200
        • Recruiting
        • Faculty of Medicine, Chiang Mai University
        • Contact:
        • Principal Investigator:
          • Rungrote Natesirinilkul, MD
  • Turkey (Türkiye)
      • Istanbul, Turkey (Türkiye), 34093
        • Recruiting
        • Istanbul Universitesi Onkoloji Enstitusu
        • Contact:
        • Principal Investigator:
          • Basak Koc, MD
      • Istanbul, Turkey (Türkiye), 34098
        • Active, not recruiting
        • Istanbul University Cerrahpsasa, Cerrahpsasa Medical Faculty Pediatric Hematology and Oncology Department
      • Van, Turkey (Türkiye), 65040
        • Recruiting
        • Yuzuncu Yil University Faculty of Medicine Department of Ophthalmology
        • Contact:
        • Principal Investigator:
          • Muhammed Batur, MD
    • Balçova
      • Izmir, Balçova, Turkey (Türkiye), 35330
        • Active, not recruiting
        • Dokuz Eylul University pediatric Pulmonology, Allergy and Clinical Immunology
  • United Kingdom
      • London, United Kingdom
        • Recruiting
        • Royal Free Hospital, Royal Free London NHS Foundation Trust
        • Contact:
        • Contact:
        • Principal Investigator:
          • Pratima Chowdary, MD
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • The University of Alabama (UAB)
        • Contact:
        • Contact:
        • Principal Investigator:
          • Christina Bemrich-Stolz, MD
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • Rush University Medical Center
        • Principal Investigator:
          • Mindy Simpson, MD
        • Contact:
        • Contact:
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • Recruiting
        • Indiana Hemophila @Thrombosis Center
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Charles Nakar, MD
        • Principal Investigator:
          • Amy D Shapiro, MD
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • University of Minnesota, Pediatric Hem/Onc & Cancer Survivorship Program
        • Contact:
        • Contact:
        • Principal Investigator:
          • Alex Boucher, MD
    • New York
      • East Setauket, New York, United States, 11733
      • Syracuse, New York, United States, 13210
        • Recruiting
        • SUNY Upstate Medical University, Pediatric Hematology/Oncology
        • Contact:
        • Contact:
        • Principal Investigator:
          • Andrea Dvorak, MD
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest University
        • Principal Investigator:
          • Amanda Blair, MD
        • Contact:
        • Contact:
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • Hemophilia Center of Western Pennsylvania
        • Contact:
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Completed
        • Vanderbilt Children's Hematology-Oncology
    • Texas
      • Forth Worth, Texas, United States, 76104
      • Houston, Texas, United States, 77030
        • Completed
        • The University of Texas Health Science Center at Houston
    • Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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).

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Define the natural history of plasminogen deficiency
Time Frame: 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
2 years
Identify factors that contribute to or correlate with disease expression and severity
Time Frame: 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
5 years
Create a specimen biobank
Time Frame: 15 years
Bank plasma, serum and DNA on consenting enrolled subjects
15 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Indiana Hemophilia &Thrombosis Center, Inc.

Collaborators

Fondazione Angelo Bianchi Bonomi

Investigators

  • Principal Investigator: Flora Peyvandi, MD, PhD, Univeristy of Milan
  • Principal Investigator: Amy D Shapiro, MD, Indiana Hemophilia &Thrombosis Center, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 18, 2018

Primary Completion (Estimated)

March 8, 2027

Study Completion (Estimated)

April 19, 2027

Study Registration Dates

First Submitted

December 28, 2018

First Submitted That Met QC Criteria

January 8, 2019

First Posted (Actual)

January 9, 2019

Study Record Updates

Last Update Posted (Estimated)

August 28, 2025

Last Update Submitted That Met QC Criteria

August 21, 2025

Last Verified

October 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HISTORY

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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