Clinical trial NCT03866590: Pyruvate Kinase Deficiency Epidemiological Study (PIECE)
Official title: Pyruvate Kinase Deficiency Epidemiological Study. An International, Multicentre, Epidemiological Observational Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pyruvate Kinase Deficiency
Keywords: Pyruvate Kinase Deficiency
Chronic anaemia
Biomarker
Lead sponsor: CENTOGENE GmbH Rostock
Sponsor class: INDUSTRY
First posted: 2019-03-07
Enrollment: 75
Sex: ALL
Minimum age (years): 5
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients older than 5 years and younger than 30 years old, with high suspicion of PK deficiency, due to chronic anaemia or cholelithiasis or cholecystitis of undetermined aetiology

Brief summary: Pyruvate kinase deficiency (PKD) is the most common red cell glycolytic enzyme defect causing hereditary non-spherocytic hemolytic anemia, caused by mutations in the PKLR gene. The main goal of this study is the diagnosis of pyruvate kinase deficiency in patients who exhibit chronic anaemia and/or splenomegaly and/or judiance and/or hyperbilirubinemia and/or history of prolonged neonatal jaundice and/ or cholelithiasis of undetermined aetiology.

Detailed description: Pyruvate kinase deficiency is the most common red cell glycolytic enzyme defect causing hereditary non-spherocytic hemolytic anemia, caused by mutations in the PKLR gene. PKLR encodes a pyruvate kinase that catalyzes the transphosphorylation of phosphoenolpyruvate into pyruvate and ATP. The current treatment options are red cell transfusions, chelation and splenectomy.

This is an international, multicentre, epidemiological and observational study.

The patients fulfilling the inclusion criteria will be enrolled into the Study and genetically tested for PKLR mutations via Next generation sequencing (NGS). Any mutation being detected by NGS, will be confirmed by Sanger sequencing.

PKLR-positive samples (homozygous or compound heterozygous for pathogenic variants) will be analysed for the identification of potential biomarkers via liquid chromatography multiple reaction-monitoring mass spectrometry (LC/MRM-MS) and compared to a merged control samples in order establish a PKD specific biomarker.

Eligibility criteria: INCLUSION CRITERIA:

* Informed consent is obtained from the participant or legal representative
* The participant is equal or older than 5 years or equal or younger than 30 years old
* The participant exhibits the following symptoms of no obvious etiology:
* chronic anaemia and/or
* splenomegaly and/or
* jaundice and/or
* cholelithiasis and/or
* cholecystitis and/or
* hyperbilirubinemia and/or
* history of prolonged neonatal jaundice
* The participant is clinically diagnosed with PK deficiency

EXCLUSION CRITERIA:

* Inability to provide informed consent
* The participant does not suffer from chronic anaemia and splenomegaly and jaundice and cholelithiasis and cholecystitis and hyperbilirubinemia and history of prolonged neonatal jaundice
* The etiology of chronic anaemia or splenomegaly or jaundice or cholelithiasis or cholecystitis or kernicterus is clearly determined and is not due to PK deficiency
* The participant is younger than 5 years or older than 30 years old
* Previously enrolled in the PIECE Study
* Participant in custody

Primary outcomes:
measure: Identification of 100 PKLR positive participants out of a cohort of 16,000 PK deficiency-suspected cases
timeFrame: 24 months
Secondary outcomes:
measure: Biomarker/s establishment in PKLR-positive cohort
timeFrame: 24 months
Other outcomes:
Locations:
city: Pembroke Pines
country: United States
facility: Intervent Clinical Research Center
state: Florida
Study officials:
affiliation: CENTOGENE GmbH
name: Peter Bauer, M.D.
role: STUDY_CHAIR
References:
citation: Beutler E, Gelbart T. Estimating the prevalence of pyruvate kinase deficiency from the gene frequency in the general white population. Blood. 2000 Jun 1;95(11):3585-8.
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: Carey PJ, Chandler J, Hendrick A, Reid MM, Saunders PW, Tinegate H, Taylor PR, West N. Prevalence of pyruvate kinase deficiency in northern European population in the north of England. Northern Region Haematologists Group. Blood. 2000 Dec 1;96(12):4005-6. No abstract available.