Pyruvate Kinase Deficiency Natural History Study (PKD NHS)

Pyruvate Kinase Deficiency (PKD) Natural History Study

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.

Study Overview

• Status: Completed
• Conditions: Pyruvate Kinase Deficiency; Congenital Non-Spherocytic Hemolytic Anemia

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.

• Study Type: Observational
• Enrollment (Actual): 254

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine
• Czechia
  • Olomouc, Czechia
    • Fakultní nemocnice Olomouc
• Germany
  • Berlin, Germany
    • Charite Berlin
  • Freiburg, Germany, 79106
    • University of Freiburg
  • Heidelberg, Germany, 69120
    • UniversitätsKlinikum Heidelberg, Zentrum für Kinder- und Jugendmedizin Klinik Kinderheilkunde III
  • Kassel, Germany, 34125
    • Klinikum Kassel
  • Munich, Germany, 80337
    • Klinikum der Universität München, Center for Pediatric Hematology/Hemostaseology
• Italy
  • Milan, Italy, 20122
    • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
• Netherlands
  • Utrecht, Netherlands, 3508GA
    • UMC Utrecht
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Phoenix Children's Hospital
  • California
    • Palo Alto, California, United States, 94305
      • Stanford University
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Children's Hospital of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
    • Worcester, Massachusetts, United States, 01605
      • University of Massachusetts Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University School of Medicine
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • CHILDREN'S MERCY HOSPITALS & CLINICS
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
    • Middlefield, Ohio, United States, 44062
      • DDC Clinic for Special Needs Children
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Strasburg, Pennsylvania, United States, 17579
      • Central Pennsylvania Clinic
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah
  • Vermont
    • Burlington, Vermont, United States, 05405
      • University of Vermont College of Medicine & University of Vermont Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with Pyruvate Kinase Deficiency of all ages

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Pyruvate Kinase Deficiency; Patients of all ages with Pyruvate Kinase Deficiency

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
transfusion burden in splenectomized and non-splenectomized participants	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
patient-reported outcomes	EuroQoL-5D-5L, Functional Assessment of Cancer Therapy-Anemia (FACT-An), Pediatric Quality of Life Inventory 4.0 (pedsQL 4.0), Pediatric Functional Assessment of Chronic Illness-Fatigue (pedsFACIT-F), Patient Reported Outcomes Measurement Information System Fatigue (PROMIS Fatigue)	enrollment, annually, up to 2 years
changes over time in hemoglobin and markers of hemolysis		enrollment, annually, up to 2 years
prevalence and severity of iron overload		enrollment, annually, up to 2 years

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: Agios Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (ACTUAL): December 1, 2019
• Study Completion (ACTUAL): May 1, 2020

Study Registration Dates

• First Submitted: January 28, 2014
• First Submitted That Met QC Criteria: January 31, 2014
• First Posted (ESTIMATE): February 3, 2014

Study Record Updates

• Last Update Posted (ACTUAL): May 22, 2020
• Last Update Submitted That Met QC Criteria: May 20, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: anemia; health-related quality of life; jaundice; hemolytic anemia; splenectomy; Hematologic diseases; pyruvate kinase deficiency; enzymopathy
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Anemia, Hemolytic, Congenital; Anemia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Congenital Nonspherocytic; Pyruvate Metabolism, Inborn Errors
• Other Study ID Numbers: P00010515

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO