Clinical trial NCT02053480: Pyruvate Kinase Deficiency Natural History Study
Official title: Pyruvate Kinase Deficiency (PKD) Natural History Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pyruvate Kinase Deficiency
Congenital Non-Spherocytic Hemolytic Anemia
Keywords: pyruvate kinase deficiency
hemolytic anemia
anemia
enzymopathy
jaundice
splenectomy
health-related quality of life
Hematologic diseases
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: Agios Pharmaceuticals, Inc.
First posted: 2014-02-03
Enrollment: 254
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Pyruvate Kinase Deficiency of all ages

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.

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.

Primary outcomes:
measure: transfusion burden in splenectomized and non-splenectomized participants
timeFrame: 12 weeks
Secondary outcomes:
measure: patient-reported outcomes
timeFrame: enrollment, annually, up to 2 years
measure: changes over time in hemoglobin and markers of hemolysis
timeFrame: enrollment, annually, up to 2 years
measure: prevalence and severity of iron overload
timeFrame: enrollment, annually, up to 2 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Atlanta
country: United States
facility: Children's Hospital of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Lurie Children's Hospital
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University School of Medicine
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospitals & Clinics
state: Missouri
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Middlefield
country: United States
facility: DDC Clinic for Special Needs Children
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Strasburg
country: United States
facility: Central Pennsylvania Clinic
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Burlington
country: United States
facility: University of Vermont College of Medicine & University of Vermont Medical Center
state: Vermont
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: Olomouc
country: Czechia
facility: Fakultni Nemocnice Olomouc
city: Berlin
country: Germany
facility: Charite Berlin
city: Freiburg
country: Germany
facility: University of Freiburg
city: Heidelberg
country: Germany
facility: UniversitätsKlinikum Heidelberg, Zentrum für Kinder- und Jugendmedizin Klinik Kinderheilkunde III
city: Kassel
country: Germany
facility: Klinikum Kassel
city: Munich
country: Germany
facility: Klinikum der Universität München, Center for Pediatric Hematology/Hemostaseology
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.