Mutational Analysis as a Prognostic and Predictive Marker of Cardiovascular (CVD) Disease in Patients With Myelodysplasia

September 30, 2019 updated by: Sunnybrook Health Sciences Centre

Mutational Analysis as a Prognostic and Predictive Marker of Cardiovascular Disease in Patients With Myelodysplasia

This study evaluates the relationship between myelodysplastic syndromes (MDS) and cardiovascular disease. MDS patients will be evaluated for the presence of mutations and whether they are associated with an increased risk of heart disease (CVD) and inflammation compared to healthy adults. Patients without symptoms of CVD will receive CT scans to assess for hidden disease and if that is related to their mutations.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Myelodysplastic syndromes (MDS) are a type of blood cancer that can cause infection or bleeding because they prevent the formation of blood components and may lead to leukemia and death. MDS can arise from changes (or mutations) to a patient's DNA. MDS patients have increased risk of heart disease compared to healthy adults. The investigators will look for links between mutations in MDS patients and increased risk of heart disease. They will also use "CT imaging" to see if MDS patients have asymptomatic artery disease but may lead to heart disease in the future and if that is related to their mutations. The researcher will try to link mutations in MDS patients to markers of inflammation and to the amount of artery disease on CT imaging to look for patterns. The goal is to find certain mutations that are associated with inflammation and heart disease. This may ultimately allow hematologists to test MDS patients with these mutations for heart disease and/or treat them early so they have a better and longer life.

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Sciences Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of: myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), Chronic myelomonocytic leukemia leukemia (CMML), or low-blast acute myeloid leukemia (AML, blasts 20-29%) less than 24 months ago
  • Alive and registered in the MDS-Canada (MDS-CAN) database
  • Known comorbidity history and known history of cardiovascular disease
  • Able to provide peripheral blood sample for cytokine analysis
  • Able top provide samples for next generation sequencing (NGS) - if diagnosis 0-6 months ago: peripheral blood; if diagnosis 6-24 months ago: diagnostic bone marrow aspirate slides or peripheral blood

Exclusion Criteria:

  • MDS/MPN patients other than CMML due to higher prevalence of Janus Kinase 2 (JAK2) mutation (a known risk factor for CVD)
  • Disease progression without available diagnostic bone marrow slides for NGS

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: SCREENING
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: MDS patients
All Canadian MDS patients on the MDS-database to be included.
Genetic: Genetic Mutations
DNA sequencing for mutations to be obtained by bloodwork within 6 months of diagnosis, or by accessing diagnostic bone marrow aspirate slides.
Other: Inflammatory and lipid markers
Bloodwork to be done for lipid profile, c-reactive protein (CRP), and multiplex chemokine/cytokine analysis.
Other: Computed Tomography (CT) of the heart
Sunnybrook Patients with no history of cardiovascular disease [ex: past/present coronary artery disease (CAD), peripheral vascular disease (PVD), angina, myocardial infarction (MI), stroke, transient ischemic attack (TIA), or stents], not pregnant, and able to undergo CT will receive a CT of the heart to look for and quantify any occult coronary artery disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure the allelic frequency and type of myeloid cancer-associated mutations in MDS patients diagnostic bone marrow aspirates or slides
Time Frame: 2 years
Screen for Presence of myeloid-cancer associated mutations and their variant allele frequencies (VAF) at diagnosis of MDS as measured through next generation sequencing of 40 myeloid genes.
2 years
Screen for occult and potentially clinically significant CAD in MDS patients by means of coronary CT
Time Frame: 2 years

Patients at Sunnybrook hospital with no pre-existing history of CAD who receive CT of the heart and found to harbour occult CAD by means of coronary calcium scoring:

  1. zero calcium (No CAD)
  2. 1-400: mild-moderate calcification
  3. >400: severe calcification
2 years
Identify any correlation between selected myeloid mutations and/or their VAF with the presence of pre-existing incident or occult CAD
Time Frame: 2 years
Comparing the presence of myeloid-cancer associated mutations and their variant allele frequencies (VAF) at diagnosis of MDS as measured through next generation sequencing of 40 myeloid genes between patients with pre-existing/occult CAD and those without.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Track how often newly discovered CAD from coronary CT leads to further intervention or changes in monitoring
Time Frame: 2 years

The investigators will track any interventions in patients without a prior history of CAD who who are discovered to have occult CAD by coronary CT. This includes number of patients who were recommended:

  1. medical management of CAD
  2. Referral to clinical cardiologist
  3. Invasive angiography
2 years
Screen for serum inflammatory cytokines in the blood of patients with incident or occult CAD
Time Frame: 2 years
Measure TNFa, IL-1beta, IL-6 and an array of other inflammatory cytokines (to be determined) in the peripheral blood upon enrollment
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sunnybrook Health Sciences Centre

Collaborators

Queen's University
Ontario Molecular Pathology Research Network

Investigators

  • Principal Investigator: Rashmi S Goswani, MD, Sunnybrook Health Sciences Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

September 1, 2019

Primary Completion (ANTICIPATED)

September 1, 2021

Study Completion (ANTICIPATED)

September 1, 2021

Study Registration Dates

First Submitted

August 23, 2019

First Submitted That Met QC Criteria

September 30, 2019

First Posted (ACTUAL)

October 1, 2019

Study Record Updates

Last Update Posted (ACTUAL)

October 1, 2019

Last Update Submitted That Met QC Criteria

September 30, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MDS CVD

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cardiovascular Diseases

Clinical Trials on Genetic Mutations

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Congo

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe