Clinical trial NCT06295081: TREAT Study - Improving the Interpretation of Troponin Concentrations Following Exercise and Their Clinical Significance
Official title: TREAT Study - Improving the Interpretation of Troponin Concentrations Following Exercise and Their Clinical Significance
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Coronary Artery Disease
Keywords: coronary artery disease
exercise
athlete
troponin
radiology
biomarker
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Maastricht University Medical Center
First posted: 2024-03-06
Enrollment: 1015
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1500 Athletes will be recruited at mass-participation long-distance exercise events and stratified for type of sport (e.g. walking, cycling, running). Recruitment will take place via official websites/newsletters of the associated exercise events and social media channels.

Our research has extensive experience performing studies in mass-participation exercise events, such as the Four Days Marches, Seven Hills Run, Eindhoven Marathon, Amsterdam Marathon, Maastricht Marathon in which we successfully included hundreds of participants. Therefore, we expect no difficulty to reach our target number of included participants.

Brief summary: The goal of this observational study is to learn about cardiac biomarker release following exercise in amateur athletes.

The main questions it aims to answer are:

Question 1: What are the reference values for exercise-induced cardiac troponin elevations following walking, cycling and running exercise? Hypothesis 1: We hypothesize that the exercise-induced cTn release is different following walking, cycling and running exercise. Therefore, we will establish reference values for post-exercise cTn concentrations across each of these sport types.

Question 2: Is the prevalence of (subclinical) coronary artery disease higher in individuals with high post-exercise cardiac troponin concentrations in comparison to individuals with low post-exercise cardiac troponin concentrations? Hypothesis 2: We hypothesize that athletes with the highest post-exercise cTn concentrations have a higher prevalence of coronary atherosclerosis compared to athletes matched for sex and age with the lowest post-exercise cTn concentrations.

Question 3: What is the association between post-exercise cardiac troponin concentrations and major adverse cardiovascular events (MACE) and mortality during long-term follow-up? Hypothesis 3: We hypothesize that post-exercise cTn concentrations beyond the 99th percentile are associated with an increased risk for MACE and mortality during follow-up.

This study consists of three phases:

Phase 1: two or three visits to the study location for (amongst other measurements) blood draws to assess cardiac troponin concentrations

Phase 2: CT scan of the heart in 10% of participants to assess the prevalence of (subclinicial) coronary artery disease.

Phase 3: longitudinal follow-up to assess the incidence of major adverse cardiovascular events and mortality during 20-year follow-up.

Participants will visit our study centre two, three or four times:

Visit 1: baseline measurements including height, weight, body composition and blood pressure will be obtained and a blood sample will be drawn.

Visit 2: a blood sample will be drawn and activity data will be obtained from participants' own sports watch or bike computer.

Optional visit 3: a blood sample will be drawn. Visit 4: 10% of participants will undergo a cardiac CT scan to assess the prevalence of (subclinical) coronary artery disease.

Detailed description: For a detailed description, please see the attached study protocol under 'Documents'.

Eligibility criteria: Inclusion criteria:

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

* Participant of an affiliated mass-participation exercise event with a:

  * Walking distance ≥20 km
  * Cycling distance ≥100 km
  * Running distance ≥15 km
* Age: ≥ 40 and \<70 years old
* Able to understand and perform study related procedures

For Phase 2 of the study (i.e. assessment of (sub)clinical coronary artery disease), the following additional criteria are present:

• Free from (known) cardiovascular diseases

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in Phase 2 of the study:

* Renal transplantation in the past
* Contrast nephropathy in the past
* estimated glomerular filtration rate (eGFR) \< 30 ml/min
* Atrial fibrillation (heart rhythm disorder)
* Previous allergic reaction to iodine contrast
* Participation in other studies involving radiation
* Not willing to be informed about potential incidental findings from the CT-scan

Primary outcomes:
measure: High-sensitivity cardiac troponin I (hs-cTnI)
timeFrame: Within 5 days before exercise event, within 6 hours post-exercise cessation, 24-48 hours post-exercise cessation
measure: High-sensitivity cardiac troponin T (hs-cTnT)
timeFrame: Within 5 days before exercise event, within 6 hours post-exercise cessation, 24-48 hours post-exercise cessation
Secondary outcomes:
measure: General CT scan data
timeFrame: within 3 months after inclusion
measure: Coronary artery calcification score
timeFrame: within 3 months after inclusion
measure: Coronary stenosis and plaque characteristics
timeFrame: within 3 months after inclusion
measure: Computed tomography derived Fractional Flow Reserve
timeFrame: within 3 months after inclusion
measure: Incidence of mortality
timeFrame: 5 years after inclusion, 10 years after inclusion, 15 years after inclusion, 20 years after inclusion. Time-to-event: From the date of inclusion until the date of first documented date of death (from any cause), assessed up to 20 years after inclusion
measure: Incidence of major adverse cardiovascular events
timeFrame: At 1/2/3/4/5/6/7/8/9/10/11/12/13/14/15/16/17/18/19/20 years after inclusion.Time-to-event: From the date of inclusion until the date of first documented major adverse cardiovascular event, assessed up to 20 years after inclusion.
Other outcomes:
measure: Participant characteristics (personal info)
timeFrame: At day of inclusion
measure: Participant characteristics (baseline measurements)
timeFrame: At day of inclusion
measure: Participant characteristics (Exercise characteristics):
timeFrame: Visit 2 (within 6 hours post-exercise cessation)
measure: Medical History questionnaire, part 1 (general info and cardiovascular complaints)
timeFrame: Within 1 week following inclusion
measure: Medical History questionnaire, part 2 (diseases and/or conditions)
timeFrame: Within 1 week following inclusion
measure: Medical History questionnaire, part 3 (family history, COVID-19 info and medication use)
timeFrame: Within 1 week following inclusion
measure: Exercise History questionnaire, part 1 (exercise history, participation in endurance races and current training status)
timeFrame: Within 1 week following inclusion
measure: Exercise History questionnaire, part 2 (strength exercise)
timeFrame: Within 1 week following inclusion
measure: Other biomarker concentrations in blood
timeFrame: At day of inclusion
Locations:
city: Nijmegen
country: Netherlands
facility: RadboudUMC
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: Thijs Eijsvogels, PhD
role: PRINCIPAL_INVESTIGATOR
References: