Pyruvate Kinase Deficiency Natural History Study (PKD NHS)

• ClinicalTrials.gov Identifier: NCT02053480
• Recruitment Status: Completed
• First Posted: February 3, 2014
• Last Update Posted: May 22, 2020
• Sponsor: Boston Children's Hospital
• Collaborator: Agios Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Rachael Grace, Boston Children's Hospital

Study Description

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.

Condition or disease
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 Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 254 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 2 Years
• Official Title: Pyruvate Kinase Deficiency (PKD) Natural History Study
• Study Start Date: December 2013
• Actual Primary Completion Date: December 2019
• Actual Study Completion Date: May 2020

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. transfusion burden in splenectomized and non-splenectomized participants [ Time Frame: 12 weeks ]

Secondary Outcome Measures :

1. patient-reported outcomes [ Time Frame: enrollment, annually, up to 2 years ]
   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)
2. changes over time in hemoglobin and markers of hemolysis [ Time Frame: enrollment, annually, up to 2 years ]
3. prevalence and severity of iron overload [ Time Frame: enrollment, annually, up to 2 years ]

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients with Pyruvate Kinase Deficiency of all ages

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.

Contacts and Locations

Locations

United States, Arizona

Phoenix Children's Hospital

Phoenix, Arizona, United States, 85006

United States, California

Stanford University

Palo Alto, California, United States, 94305

United States, Georgia

Children's Hospital of Atlanta

Atlanta, Georgia, United States, 30342

United States, Illinois

Lurie Children's Hospital

Chicago, Illinois, United States, 60611

United States, Massachusetts

Boston Children's Hospital

Boston, Massachusetts, United States, 02115

University of Massachusetts Medical Center

Worcester, Massachusetts, United States, 01605

United States, Michigan

Wayne State University School of Medicine

Detroit, Michigan, United States, 48201

United States, Mississippi

University of Mississippi Medical Center

Jackson, Mississippi, United States, 39216

United States, Missouri

Children's Mercy Hospitals & Clinics

Kansas City, Missouri, United States, 64108

United States, New York

Weill Cornell Medical College

New York, New York, United States, 10065

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Ohio

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

DDC Clinic for Special Needs Children

Middlefield, Ohio, United States, 44062

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Central Pennsylvania Clinic

Strasburg, Pennsylvania, United States, 17579

United States, Tennessee

St. Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105

United States, Texas

Baylor College of Medicine

Houston, Texas, United States, 77030

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84108

United States, Vermont

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

Burlington, Vermont, United States, 05405

Canada, Ontario

McMaster University

Hamilton, Ontario, Canada, L8N 3Z5

University Health Network

Toronto, Ontario, Canada, M5G 2C4

Canada, Quebec

CHU Sainte-Justine

Montreal, Quebec, Canada, H3T 1C5

Czechia

Fakultni Nemocnice Olomouc

Olomouc, Czechia

Germany

Charite Berlin

Berlin, Germany

University of Freiburg

Freiburg, Germany, 79106

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

Heidelberg, Germany, 69120

Klinikum Kassel

Kassel, Germany, 34125

Klinikum der Universität München, Center for Pediatric Hematology/Hemostaseology

Munich, Germany, 80337

Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Italy, 20122

Netherlands

UMC Utrecht

Utrecht, Netherlands, 3508GA

Sponsors and Collaborators

Boston Children's Hospital

Agios Pharmaceuticals, Inc.

More Information

Additional Information:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Rachael Grace, Principal Investigator, PKD Natural History Study, Boston Children's Hospital
• ClinicalTrials.gov Identifier: NCT02053480
• Other Study ID Numbers: P00010515
• First Posted: February 3, 2014
• Last Update Posted: May 22, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Rachael Grace, Boston Children's Hospital:

pyruvate kinase deficiency; hemolytic anemia; anemia; enzymopathy; jaundice; splenectomy; health-related quality of life; Hematologic diseases

Additional relevant MeSH terms:

Anemia; Anemia, Hemolytic; Anemia, Hemolytic, Congenital Nonspherocytic; Pyruvate Metabolism, Inborn Errors; Hemolysis; Hematologic Diseases; Pathologic Processes; Anemia, Hemolytic, Congenital; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases