Impact of Epigenetic Age on Clinic-biological Presentation and Prognosis in Myeloproliferative Neoplasms Epigenetic Age in Myeloproliferative Neoplasms (EpiC) (EpiC)
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ClinicalTrials.gov Identifier: NCT06022328 |
Recruitment Status :
Recruiting
First Posted : September 1, 2023
Last Update Posted : March 7, 2024
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Condition or disease | Intervention/treatment |
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Myeloproliferative Neoplasm | Biological: Assessment of the epigenetic age |
Myeloproliferative Neoplasia (MPN) are hematological malignancies characterized by the excessive production of myeloid cells. They include Essential Thrombocythemia (ET), Polycythemia Vera (VP) and Primary Myelofibrosis (PMF). Thrombosis are the most frequent complications and are largely responsible for the morbidity and mortality observed in ET and PV patients. The most feared complications are hematological transformations (into myelofibrosis for PV and ET, into acute myeloid leukemia for PV, ET and PMF). The prognostic assessment of MPN patients is mainly based on clinical data. Although recent studies have shown that certain mutations are associated with a poorer prognosis, age remains the main risk factor affecting survival in MPN patients. Recent studies have shown that DNA methylation can be used to determine an "epigenetic age". Interestingly, this epigenetic age is associated with the development of cardiovascular disease and cancer.
In this project, the epigenetic age of MPN patients will be determined by studying the DNA methylation at diagnosis using the Infinium Human MethylationEPIC kit (Illumina). Epigenetic age will be determined with the most commonly used epigenetic clocks (DNAmAge, DNAmHannum, DNAmPhenoAge, DNAmSkinClock, DNAmGrimAge, intrinsic epigenetic age acceleration, extrinsic epigenetic age acceleration). It will be searched for an association between accelerated epigenetic aging (as assessed by the difference between epigenetic age and chronological age) and the type of MPN, the clinical and biological presentation at diagnosis (including the mutational profile of patients) and the occurrence of thrombosis and hematological evolution into myelofibrosis and/or acute leukemia.
Study Type : | Observational |
Estimated Enrollment : | 120 participants |
Observational Model: | Cohort |
Time Perspective: | Retrospective |
Official Title: | Impact of Epigenetic Age on Clinic-biological Presentation and Prognosis in Myeloproliferative Neoplasms Epigenetic Age in Myeloproliferative Neoplasms (EpiC) |
Actual Study Start Date : | December 15, 2023 |
Estimated Primary Completion Date : | December 2024 |
Estimated Study Completion Date : | December 2024 |
Group/Cohort | Intervention/treatment |
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Patients with ET
45 patients with ET:
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Biological: Assessment of the epigenetic age
Retrospective assessment of the epigenetic age on DNA samples obtained at diagnosis |
Patients with PV
45 patients with PV
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Biological: Assessment of the epigenetic age
Retrospective assessment of the epigenetic age on DNA samples obtained at diagnosis |
Patients with PMF
20 patients with PMF:
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Biological: Assessment of the epigenetic age
Retrospective assessment of the epigenetic age on DNA samples obtained at diagnosis |
Patients without MPN
10 patients without MPN
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Biological: Assessment of the epigenetic age
Retrospective assessment of the epigenetic age on DNA samples obtained at diagnosis |
- Accelerated ageing of patients [ Time Frame: At inclusion, up to 1 year after diagnosis ]Accelerated ageing will be defined as an increased difference between the epigenetic age (calculated from DNA methylation data with the different molecular clocks described: DNAmAge, DNAmHannum, DNAmPhenoAge, DNAmSkinClock, DNAmGrimAge, intrinsic epigenetic age acceleration, extrinsic epigenetic age acceleration) and the chronological age
- Type of MPN (ET, PV or PMF) at diagnosis [ Time Frame: At inclusion, up to 1 year after diagnosis ]We will study patients with a diagnosis of ET, PV or PMF as defined by the WHO classification of hematological malignancies
- Transformation into secondary myelofibrosis or acute leukemia [ Time Frame: From date of inclusion until documentation of the event, assessed up to 5 years ]Evolution toward secondary myelofibrosis or acute leukemia will be defined according to the WHO classification of hematological malignancies
- Occurrence of thrombosis prior to diagnosis or during follow-up of the disease [ Time Frame: Between 1 year before and 2 years after MPN diagnosis ]Occurrence of myocardial infarction, ischemic stroke, deep vein thrombosis, pulmonary embolism, splanchnic thrombosis or any other significant thrombosis. Tinnitus, vertigo, headaches, erythromelalgia as well as superficial vein thrombosis will not be considered as thrombotic events
- Leukocytes [ Time Frame: At inclusion, up to 1 year after diagnosis ]Leukocytes level on blood count in G/L
- Platelets [ Time Frame: At inclusion, up to 1 year after diagnosis ]Platelet level on blood count in G/L
- Granulocytes [ Time Frame: At inclusion, up to 1 year after diagnosis ]Granulocytes level on blood count in G/L
- Monocytes [ Time Frame: At inclusion, up to 1 year after diagnosis ]Monocytes level on blood count in G/L
- Hemoglobin [ Time Frame: At inclusion, up to 1 year after diagnosis ]Hemoglobin level on blood count in g/dL
- Hematocrit [ Time Frame: At inclusion, up to 1 year after diagnosis ]Hematocrit level on blood count in %
- Additional somatic mutation [ Time Frame: At inclusion, up to 1 year after diagnosis ]In up to 50% of MPN patients, genetic variants can be detected in genes such as DNMT3A, TET2, ASXL1, SRSF2, SF3B1, U2AF1, EZH2 or TP53. We will determine which somatic genetic variant is detected by high throughput sequencing
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Sampling Method: | Probability Sample |
Inclusion Criteria:
For the 110 patients with MPN:
- Patients with PV, ET or PMF
- DNA extracted from purified granulocytes at time of diagnosis
- No treatment likely to impact DNA methylation (chemotherapy, immunosuppressants in particular)
For the 10 subjects without MPN:
- Absence of hematological malignancy
- Search for JAK2V617F mutation in the context of reactive thrombocytosis or secondary polycythemia
- Absence of treatment likely to impact DNA methylation (chemotherapy, immunosuppressants in particular)
Exclusion Criteria:
For the 110 patients with MPN:
- Patients without PV, ET or PMF
- Patients without purified granulocytes DNA available at time of diagnosis
- Patients treated by cytoreductive drug, demethylating agent, chemotherapy or immunosuppressive therapy at the time of DNA sampling
- Patients with less than 2 years' follow-up
For the 10 subjects in NMP :
- Patients with hematological malignancy and/or solid cancer
- Patients treated by cytoreductive drug, demethylating agent, chemotherapy or immunosuppressive therapy at the time of DNA sampling
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06022328
Contact: Olivier MANSIER | olivier.mansier@chu-bordeaux.fr |
France | |
CHU de Bordeaux, service Hématologie Biologique | Recruiting |
Bordeaux, France | |
Contact: Olivier MANSIER olivier.mansier@chu-bordeaux.fr |
Responsible Party: | University Hospital, Bordeaux |
ClinicalTrials.gov Identifier: | NCT06022328 |
Other Study ID Numbers: |
CHUBX 2023/15 |
First Posted: | September 1, 2023 Key Record Dates |
Last Update Posted: | March 7, 2024 |
Last Verified: | March 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Myeloproliferative Neoplasm Epigenetic age Thrombosis Myelofibrosis Leukemia |
Neoplasms Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases |