Pyruvate Kinase DeficiencyPIECENCT03866590
Pyruvate Kinase Deficiency Epidemiological Study (PIECE)
An observational study of Pyruvate Kinase Deficiency, run by CENTOGENE GmbH Rostock at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 5 to 30 years
- Conditions the study is for
- Pyruvate Kinase Deficiency
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jan 2020to 31 May 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
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
Who may be able to join
- 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
Show all 11Show fewer
- cholelithiasis and/or
- cholecystitis and/or
- hyperbilirubinemia and/or
- history of prolonged neonatal jaundice
- The participant is clinically diagnosed with PK deficiency
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Intervent Clinical Research Center
Pembroke Pines, Florida, 33024
About this study
Official title: Pyruvate Kinase Deficiency Epidemiological Study. An International, Multicentre, Epidemiological Observational Study
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.
Read the 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.
- Conditions
- Pyruvate Kinase Deficiency
- Keywords
- Pyruvate Kinase Deficiency, Chronic anaemia, Biomarker
- Medical subject headings
- Pyruvate Kinase Deficiency of Red Cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients being at risk for Pyruvate Kinase Deficiency | Patients, older than 5 years and younger than 30 years old, being at risk for Pyruvate Kinase Deficiency, due to chronic anaemia or cholelithiasis or cholecystitis of undetermined aetiology |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 24 months
Secondary outcomes (1)
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.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2019
- Study start13 Jan 2020
- Primary completion31 May 2021
- Study completion31 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Pyruvate Kinase DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- CENTOGENE GmbH Rostock
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Peter Bauer, M.D., Study chair, CENTOGENE GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03866590
- Sponsor's protocol ID
- PIECE 01-2019
- Acronym
- PIECE
- Status last verified
- Feb 2023
- First submitted
- 1 Mar 2019
- Last updated
- 9 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The plan will be defined at a later stages
Publications
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.
PubMed 10828047Grace 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.
PubMed 29549173Carey 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.
PubMed 11186276
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pyruvate Kinase Deficiency Epidemiological Study. An International, Multicentre, Epidemiological Observational Study
- ClinicalTrials.gov ID
- NCT03866590
- Acronym / sponsor ID
- PIECE / PIECE 01-2019
- Conditions
- Pyruvate Kinase Deficiency
- Keywords
- Pyruvate Kinase Deficiency, Chronic anaemia, Biomarker
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- CENTOGENE GmbH RostockIndustry (pharma, biotech, devices)
- Study start
- 13 Jan 2020 (actual)
- Primary completion
- 31 May 2021 (actual)
- Study completion
- 31 May 2021 (actual)
- First posted
- 7 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients being at risk for Pyruvate Kinase Deficiency | – | –Patients, older than 5 years and younger than 30 years old, being at risk for Pyruvate Kinase Deficiency, due to chronic anaemia or cholelithiasis or cholecystitis of undetermined aetiology |
Who may qualify
- Ages
- 5 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- 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
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Identification of 100 PKLR positive participants out of a cohort of 16,000 PK deficiency-suspected cases
Time frame: 24 months
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)
1 secondary outcome
Biomarker/s establishment in PKLR-positive cohort
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2023.
- Background: PubMed 10828047Beutler 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.
- Background: PubMed 29549173Grace 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.
- Background: PubMed 11186276Carey 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.
- Individual participant dataSharing planned: No. The plan will be defined at a later stages
Related trials for Pyruvate Kinase Deficiency
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Participants With Pyruvate Kinase Deficiency (PKD) Who Are Regularly Transfused, Followed by a 5-Year Extension Period
Pediatric Pyruvate Kinase Deficiency, Pediatric Hemolytic Anemia
Active, not recruitingObservational study
Pyruvate Kinase Deficiency Global Longitudinal Registry
Pyruvate Kinase Deficiency
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Participants With Pyruvate Kinase Deficiency (PKD) Who Are Not Regularly Transfused, Followed by a 5-Year Extension Period
Pediatric Pyruvate Kinase Deficiency, Pediatric Hemolytic Anemia
Enrolling by invitationPhase 4
A Study to Provide Access to Mitapivat for Participants Who Previously Participated in an Agios-Sponsored Mitapivat Study
Pyruvate Kinase Deficiency, Anemia, Hemolytic
Not yet recruitingPhase 1
High-Dose Vitamin C in G6PDA and Pyruvate Kinase Deficiency: A Safety Study
Pyruvate Kinase Deficiency, Glucose 6 Phosphate Dehydrogenase Deficiency
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Bauer, M.D. study chair
CENTOGENE GmbH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pyruvate Kinase Deficiency, run by CENTOGENE GmbH Rostock at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of 100 PKLR positive participants out of a cohort of 16,000 PK deficiency-suspected cases (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03866590, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2023.