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Study of Individuals Affected With Hypoplasminogenemia (HISTORY)

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ClinicalTrials.gov Identifier: NCT03797495
Recruitment Status : Recruiting
First Posted : January 9, 2019
Last Update Posted : January 9, 2019
Sponsor:
Collaborator:
Fondazione Angelo Bianchi Bonomi
Information provided by (Responsible Party):
Amy D. Shapiro, MD, 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

Condition or disease
Plasminogen Deficiency

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.


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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Other
Official Title: Hypoplasminogenemia: An International RetroSpecTive and PrOspective CohoRt StudY (HISTORY)
Actual Study Start Date : December 18, 2018
Estimated Primary Completion Date : January 18, 2023
Estimated Study Completion Date : January 18, 2024





Primary Outcome Measures :
  1. 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. 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

  3. Create a specimen biobank [ Time Frame: 15 years ]
    Bank plasma, serum and DNA on consenting enrolled subjects


Biospecimen Retention:   Samples With DNA
Whole blood, serum, and plasma will be retained. Time perspective is retrospective and prospective.


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
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).
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03797495


Contacts
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Contact: Amy D Shapiro, MD 317-871-0000 ashapiro@ihtc.org
Contact: Charles Nakar, MD 317-871-0000 cnakar@ihtc.org

Locations
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United States, Indiana
Indiana Hemophila @Thrombosis Center Recruiting
Indianapolis, Indiana, United States, 46260
Contact: Neelam Thukral, CCRC    317-871-0000 ext 373    nthukral@ihtc.org   
Contact: Charles Nakar, MD    317-871-0000    cnakar@ihtc.org   
Principal Investigator: Amy D Shapiro, MD         
Sub-Investigator: Charles Nakar, MD         
Italy
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Recruiting
Milano, Italy, 20122
Contact: Marzia Menegatti, PhD    +39 - 02/50320727    marzia.menegatti@guest.unimi.it   
Principal Investigator: Flora Peyvandi, MD,PhD         
Sponsors and Collaborators
Indiana Hemophilia &Thrombosis Center, Inc.
Fondazione Angelo Bianchi Bonomi
Investigators
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Principal Investigator: Amy D Shapiro, MD Indiana Hemophilia &Thrombosis Center, Inc.
Principal Investigator: Flora Peyvandi, MD, PhD Univeristy of Milan

Publications of Results:
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Responsible Party: Amy D. Shapiro, MD, Medical Director, Indiana Hemophilia &Thrombosis Center, Inc.
ClinicalTrials.gov Identifier: NCT03797495     History of Changes
Other Study ID Numbers: HISTORY
First Posted: January 9, 2019    Key Record Dates
Last Update Posted: January 9, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No