Pyruvate Kinase Deficiency Natural History Study

NCT ID: NCT02053480

Last Updated: 2020-05-22

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 254 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2020-05-31

Brief Summary

The purpose of this study is to describe the range and incidence of symptoms, treatments, and complications related to pyruvate kinase deficiency (PKD). Eligible patients are those of all ages with known PKD or with a hemolytic anemia and a family member with PKD. The study will collect retrospective medical history, routine clinical care data, and quality of life measures at baseline and annually for patients with PKD.

Detailed Description

The purpose of the Pyruvate Kinase Deficiency (PKD) Natural History Study is to describe the natural history of PKD and the range and incidence of symptoms, treatments, and complications related to PKD. The study will collect retrospective medical history and routine clinical care data at baseline and annually for patients with PKD. Patients without a genetic diagnosis will have a blood sample drawn for genetic diagnostic confirmation for research purposes. Understanding the clinical variation among participants with PKD, and assessing treatments specific to PKD and their outcomes will accelerate improvement in the care of patients with PKD. Understanding the natural history of PKD may be useful in the design of future interventional studies. Detailed genotypic and phenotypic characterization of the cohort will allow for continued in depth characterization of PKD. Finally, the PKD Natural History Study will identify interested participants for future PKD studies.

Primary Objectives:

1. To estimate the transfusion burden in splenectomized and non-splenectomized participants with PKD.

2. To establish a patient registry as a potential source for recruitment to future research studies in PKD.

Secondary Objectives:

1. To determine if patient-reported outcomes, including quality of life and fatigue scales, are associated with age, genotype, hemoglobin nadir, and/or transfusion burden, overall and within the subgroups of splenectomized vs. non-splenectomized participants;

2. To describe changes over time in the range of hemoglobin values and markers of hemolysis within individual participants and among participants with PKD;

3. To estimate the incidence of past splenectomy and annual splenectomy rate, as treatment for PKD;

4. To estimate the prevalence and severity and describe the treatment of hepatic and cardiac iron overload and its complications in PKD (liver, cardiac, growth defects, hypogonadotropic hypogonadism, and other endocrine defects). To describe the changes in these complications that may occur over time and by age group;

5. To estimate the prevalence of co-morbidities associated with chronic hemolysis in PKD, to identify which co-morbidities are the most common, and to determine if the prevalence and/or severity of co-morbidities change over time and by age at the time of the first appearance of the co-morbidity;

6. To determine pregnancy outcomes among participants with PKD;

7. To describe genotypic and phenotypic variation among participants and explore genotype-phenotype correlation in PKD.

Conditions

Pyruvate Kinase Deficiency; Congenital Non-Spherocytic Hemolytic Anemia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Pyruvate Kinase Deficiency

Patients of all ages with Pyruvate Kinase Deficiency

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Patients of all ages with biochemically or genetically diagnosed PKD.
• Patients with a hemolytic anemia AND a family member with genetically diagnosed PKD
• The participant or the guardian of the participant is willing and able to give written informed consent and/or assent.

Exclusion Criteria

• The participant or the guardian of the participant is unwilling or unable to give written informed consent and/or assent.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Agios Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Rachael Grace

Principal Investigator, PKD Natural History Study

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Phoenix Children's Hospital

Phoenix, Arizona, United States

Stanford University

Palo Alto, California, United States

Children's Hospital of Atlanta

Atlanta, Georgia, United States

Lurie Children's Hospital

Chicago, Illinois, United States

Boston Children's Hospital

Boston, Massachusetts, United States

University of Massachusetts Medical Center

Worcester, Massachusetts, United States

Wayne State University School of Medicine

Detroit, Michigan, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Children's Mercy Hospitals & Clinics

Kansas City, Missouri, United States

Weill Cornell Medical College

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

DDC Clinic for Special Needs Children

Middlefield, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Central Pennsylvania Clinic

Strasburg, Pennsylvania, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Baylor College of Medicine

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

University of Vermont College of Medicine & University of Vermont Medical Center

Burlington, Vermont, United States

McMaster University

Hamilton, Ontario, Canada

University Health Network

Toronto, Ontario, Canada

CHU Sainte-Justine

Montreal, Quebec, Canada

Fakultni Nemocnice Olomouc

Olomouc, , Czechia

Charite Berlin

Berlin, , Germany

University of Freiburg

Freiburg im Breisgau, , Germany

UniversitätsKlinikum Heidelberg, Zentrum für Kinder- und Jugendmedizin Klinik Kinderheilkunde III

Heidelberg, , Germany

Klinikum Kassel

Kassel, , Germany

Klinikum der Universität München, Center for Pediatric Hematology/Hemostaseology

Munich, , Germany

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

UMC Utrecht

Utrecht, , Netherlands

Countries

United States; Canada; Czechia; Germany; Italy; Netherlands

References

Grace RF, Bianchi P, van Beers EJ, Eber SW, Glader B, Yaish HM, Despotovic JM, Rothman JA, Sharma M, McNaull MM, Fermo E, Lezon-Geyda K, Morton DH, Neufeld EJ, Chonat S, Kollmar N, Knoll CM, Kuo K, Kwiatkowski JL, Pospisilova D, Pastore YD, Thompson AA, Newburger PE, Ravindranath Y, Wang WC, Wlodarski MW, Wang H, Holzhauer S, Breakey VR, Kunz J, Sheth S, Rose MJ, Bradeen HA, Neu N, Guo D, Al-Sayegh H, London WB, Gallagher PG, Zanella A, Barcellini W. Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study. Blood. 2018 May 17;131(20):2183-2192. doi: 10.1182/blood-2017-10-810796. Epub 2018 Mar 16.

Reference Type: BACKGROUND

PMID: 29549173 (View on PubMed)

van Beers EJ, van Straaten S, Morton DH, Barcellini W, Eber SW, Glader B, Yaish HM, Chonat S, Kwiatkowski JL, Rothman JA, Sharma M, Neufeld EJ, Sheth S, Despotovic JM, Kollmar N, Pospisilova D, Knoll CM, Kuo K, Pastore YD, Thompson AA, Newburger PE, Ravindranath Y, Wang WC, Wlodarski MW, Wang H, Holzhauer S, Breakey VR, Verhovsek M, Kunz J, McNaull MA, Rose MJ, Bradeen HA, Addonizio K, Li A, Al-Sayegh H, London WB, Grace RF. Prevalence and management of iron overload in pyruvate kinase deficiency: report from the Pyruvate Kinase Deficiency Natural History Study. Haematologica. 2019 Feb;104(2):e51-e53. doi: 10.3324/haematol.2018.196295. Epub 2018 Sep 13. No abstract available.

Reference Type: BACKGROUND

PMID: 30213831 (View on PubMed)

Bianchi P, Fermo E, Lezon-Geyda K, van Beers EJ, Morton HD, Barcellini W, Glader B, Chonat S, Ravindranath Y, Newburger PE, Kollmar N, Despotovic JM, Verhovsek M, Sharma M, Kwiatkowski JL, Kuo KHM, Wlodarski MW, Yaish HM, Holzhauer S, Wang H, Kunz J, Addonizio K, Al-Sayegh H, London WB, Andres O, van Wijk R, Gallagher PG, Grace RFF. Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency. Am J Hematol. 2020 May;95(5):472-482. doi: 10.1002/ajh.25753. Epub 2020 Mar 6.

Reference Type: BACKGROUND

PMID: 32043619 (View on PubMed)

Al-Samkari H, van Beers EJ, Morton DH, Eber SW, Chonat S, Kuo KHM, Kollmar N, Wang H, Breakey VR, Sheth S, Sharma M, Forbes PW, Klaassen RJ, Grace RF. Health-related quality of life and fatigue in children and adults with pyruvate kinase deficiency. Blood Adv. 2022 Mar 22;6(6):1844-1853. doi: 10.1182/bloodadvances.2021004675.

Reference Type: DERIVED

PMID: 34470054 (View on PubMed)

Other Identifiers

P00010515

Identifier Type: -

Identifier Source: org_study_id