NCT04533282: IHD-EPITRAN

Epitranscriptomic Blood Biomarkers for Coronary Artery Disease - A Prospective Cohort Study (IHD-EPITRAN)

Status unknown Last updated 12 November 2020

What this trial tests

trial testing Blood samples. in Ischemic Heart Disease in 200 participants. Status unknown.

Timeline

10 November 2020

Primary endpoint
31 December 2023

31 December 2025

Quick facts

Lead sponsor	Hospital District of Helsinki and Uusimaa
Status	Status unknown
Study type	OBSERVATIONAL
Enrollment	200
Start date	10 November 2020
Primary completion	31 December 2023
Estimated completion	31 December 2025
Sites	1 location across Finland

Drugs / interventions tested

• Blood samples.
• Collection of right atrial appendage tissue sample.
• Health Survey, Clinical symptom scaling
• Transthoracic echocardiography (TTE)

Conditions studied

• Ischemic Heart Disease — all drugs for Ischemic Heart Disease →
• Coronary Artery Disease — all drugs for Coronary Artery Disease →
• Aortic Valve Stenosis — all drugs for Aortic Valve Stenosis →
• Acute Myocardial Infarction — all drugs for Acute Myocardial Infarction →

Sponsor

Hospital District of Helsinki and Uusimaa

Who can join

Adults 18 to 80, any sex, with Ischemic Heart Disease or Coronary Artery Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Despite advancements in medical care, ischemic heart disease (IHD) remains the leading global cause of death. IHD develops through lipid accumulation into the coronary arteries with subsequent formation of larger atherogenic plaques. During myocardial infarction (MI), a plaque ruptures and subsequent occlusion leads to a death of the heart muscle. The tissue is rapidly replaced with a scar, which may later lead to heart failure (HF).

Optimally, disease biomarkers are analyzed from blood, provide insight into the disease progression and aid the evaluation of therapy efficacy. Unfortunately, no optimal biomarkers have been identified for IHD. The vast but uncounted number of patients with undiagnosed IHD, benefitting from an early diagnosis, underscore the dire need for an IHD biomarker.

Epitranscriptomics, the study of posttranscriptional modifications on RNA, has recently been properly re-established. This expanding field is uncovering a new layer of regulation, controlling processes ranging from cell division to cell death.

Over 170 modifications have been identified as posttranscriptional marks in RNA species. These modifications influence RNA metabolism, including export, stability, and translation. One the most common and intensively studied RNA modification is the N6-methyladenosine (m6A), the abundance and effects of which are determined by the interplay between its writers, readers and erasers.

Recent findings suggest a local dysregulation of the m6A dynamics in the myocardium, coalescing in signalling pathway and contractility related RNA transcripts during hypertrophy, MI and HF. While these early reports have focused on the myocardium, the role of the m6A in the circulation during IHD remains unexplored.

We hypothesize the IHD pathophysiology to be reflected in the epitranscriptome of the circulating RNA.

The objective of the IHD-EPITRAN is to identify new IHD biomarkers via cohort comparison of the blood epitranscriptomes from patients with: (1) MI related with coronary angioplasty, (2) IHD treated with elective coronary artery bypass grafting, (3) aortic valve stenosis treated with valve replacement and (4) IHD-healthy controls verified with computerized tomography imaging. The RNA fractionation is followed by the quantitative modifications analysis with mass spectrometry. Ultimately, nanopore RNA sequencing with simultaneous m6A identification in their native sequences is carried out using recently published artificial intelligence-based algorithm.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Epitranscriptomics of Ischemic Heart Disease-The IHD-EPITRAN Study Design and Objectives.
   Sikorski V, Karjalainen P, Blokhina D, Oksaharju K, et al · · 2021 · cited 11× · PMID 34205699 · DOI 10.3390/ijms22126630
2. Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome.
   Mulari S, Eskin A, Lampinen M, Nummi A, et al · · 2021 · cited 6× · PMID 34926599 · DOI 10.3389/fcvm.2021.728198
3. Decoding vascular calcification: mechanistic insights and translational strategies.
   Adelnia H, Ray S, Ta HT. · · 2026 · PMID 41665680 · DOI 10.1007/s00018-026-06086-4