Pyruvate Kinase Deficiency Epidemiological Study (PIECE)

Pyruvate Kinase Deficiency Clinical Trial

— PIECE  

Official title:

Pyruvate Kinase Deficiency Epidemiological Study. An International, Multicentre, Epidemiological Observational Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03866590
• Other study ID #: PIECE 01-2019
• Status: Completed
• Start date: January 13, 2020
• Est. completion date: May 31, 2021

Study information

• Verified date: February 2023
• Source: CENTOGENE GmbH Rostock
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: May 31, 2021
• Est. primary completion date: May 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Pyruvate Kinase Deficiency

Locations

Country	Name	City	State
United States	Intervent Clinical Research Center	Pembroke Pines	Florida

Sponsors (1)

Lead Sponsor	Collaborator
CENTOGENE GmbH Rostock

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of 100 PKLR positive participants out of a cohort of 16,000 PK deficiency-suspected cases	Number of identified pyruvate kinase deficiency patients, which showing a mutation/pathogenic variant in their PKLR gene, within a cohort of 16.000 suspected cases via using respective patients' dry blood sample for confirmatory testing (next generation sequencing of PKLR gene)	24 months
Secondary	Biomarker/s establishment in PKLR-positive cohort	The quantitative determination of small molecules within a dried blood spot sample will be validated via liquid chromatography multiple reaction-monitoring mass spectrometry, and compared with a merged control cohort. The statistically best validated molecule will be considered as a disease specific biomarker.	24 months