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Impact of Epigenetic Age on Clinic-biological Presentation and Prognosis in Myeloproliferative Neoplasms Epigenetic Age in Myeloproliferative Neoplasms (EpiC)

Study Purpose

Myeloproliferative Neoplasms (MPN) are hematological malignancies characterized by the excessive production of myeloid cells. MPN can be complicated by thrombosis and evolution into more aggressive diseases (myelofibrosis and acute leukemia). Aging remains the principal factor determining patients' survival in MPN. In recent years, DNA methylation has appeared as a mean to measure aging via the development of epigenetic clocks that have also been associated with the occurrence of thrombosis and cancer. The epiC project aims at determining epigenetic age of MPN patients and search for an association between this parameter and thrombotic/hematological complications.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Observational
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06022328
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University Hospital, Bordeaux
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries France
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Myeloproliferative Neoplasm
Additional Details

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.

Arms & Interventions

Arms

: Patients with ET

45 patients with ET: 15 without thrombotic event (neither at diagnosis nor during follow-up) 15 with thrombotic events (thrombosis at diagnosis or within 2 years of diagnosis) 15 who progressed to myelofibrosis or AML during follow-up

: Patients with PV

45 patients with PV 15 without thrombotic event (neither at diagnosis nor during follow-up) 15 with thrombotic event (thrombosis at diagnosis or within 2 years of diagnosis) 15 who progressed to myelofibrosis or AML during follow-up

: Patients with PMF

20 patients with PMF: 10 without transformation into AML 10 patients who progressed to AML

: Patients without MPN

10 patients without MPN

Interventions

Biological: - Assessment of the epigenetic age

Retrospective assessment of the epigenetic age on DNA samples obtained at diagnosis

Contact a Trial Team

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International Sites

Bordeaux, France

Status

Recruiting

Address

CHU de Bordeaux, service Hématologie Biologique

Bordeaux, ,

Site Contact

Olivier MANSIER

[email protected]