TREAT Study - Improving the Interpretation of Troponin Concentrations Following Exercise and Their Clinical Significance

Coronary Artery Disease Clinical Trial

— TREAT  

Official title:

TREAT Study - Improving the Interpretation of Troponin Concentrations Following Exercise and Their Clinical Significance

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06295081
• Other study ID #: NL79864.091.22
• Secondary ID: 112927
• Status: Recruiting
• Start date: June 15, 2022
• Est. completion date: July 1, 2044

Study information

• Verified date: January 2024
• Source: Radboud University Medical Center
• Contact: Sylvan Janssen, MSc
• Phone: +31243613416
• Email: sylvan.janssen[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: July 1, 2044
• Est. primary completion date: July 1, 2024
• Gender: All
• Age group: 40 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Other:
• Exercise exposure
Exercise is NOT part of our study protocol. Participants will voluntarily participate in a mass-participation exercise event (i.e. walking, cycling or running). Participation in this exercise event is voluntary and independent from participation in this study (i.e. participants would also take part in the exercise event if they did not participate in our study). Therefore, we do not consider the performed exercise an intervention or part of our study protocol. Hence, we consider our study design to be observational. Participants will perform exercise during a mass-participation exercise event, stratified for type of exercise (walking versus running versus cycling; n=500 each). The mass-participation exercise events have a sport-specific minimum distance of: a mass-participation exercise event with a: Walking distance =20 km Cycling distance =100 km Running distance =15 km

Locations

Country	Name	City	State
Netherlands	RadboudUMC	Nijmegen	Gelderland

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University Medical Center	Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Participant characteristics (personal info)	Sex (male/female); name; e-mail address; phone number; place of residence; date of birth (dd-mm-yyyy); mass-participation sports event; distance (km).; If included in the study: Participant identification number (TREAT…).	At day of inclusion
Other	Participant characteristics (baseline measurements)	Blood pressure: Systolic and diastolic blood pressure (mmHg) at rest; heart rate at rest (bpm).; Anthropometry: Height (cm); weight (kg); BMI (kg/m2); body fat percentage (%); fat-free mass (kg ).; BMI: body mass index;	At day of inclusion
Other	Participant characteristics (Exercise characteristics):	Exercise type (walking/cycling/running); exercise distance (km); start and finish time (hh:mm); pause time (hh:mm); exercise duration (hh:mm); average speed (km/h); average speed (min/km); average heart rate (bpm).; If used a sports watch or bike computer: .FIT-file or .CSV-file of activity.	Visit 2 (within 6 hours post-exercise cessation)
Other	Medical History questionnaire, part 1 (general info and cardiovascular complaints)	General: level of education (primary education/preparatory vocational education/secondary vocational education/university of applied sciences/university bachelor/university master/PhD/other); ethnicity (Caucasian(European)/Afro-American/Asian/mixed/other); smoking (yes/no but I used to smoke/never); alcohol consumption (units/week); frequency of being active for =30 minutes (days/week); ever used performance-enhancing substances (yes/no, if yes: which substances).; Cardiovascular complaints and/or procedures: cardiovascular complaints [e.g. dyspnoea, chest pain, fainting, palpitations] (yes/no); ever had coronary stenting or coronary artery bypass grafting (yes/no, if yes: reason of procedure, year and hospital where procedure was performed).	Within 1 week following inclusion
Other	Medical History questionnaire, part 2 (diseases and/or conditions)	Diseases and/or conditions (all yes/no, if yes, date of diagnosis (dd-mm-yyyy)): atherosclerosis; stroke/TIA/CVA; atrial fibrillation; COPD/lung diseases; embolism [anywhere other than lungs]; erectile disorders; intermittent claudication; myocardial fibrosis; fainting; conduction disorders; heart attack/myocardial infarction; heart failure; heart rhythm disorder; heart murmur; hypertrophic cardiomyopathy; lung embolism; kidney failure or kidney disorders; myocarditis; angina/chest pain; rheumatic disorders; diabetes mellitus; thrombosis; vascular dementia; hypertension; hypercholesterolaemia; hypotension; narrowed/occluded artery; dilation of artery [aneurysm], disease of lymph nodes or vessels, other diseases (yes/no, if yes: which disease and date of diagnosis (mm-yyyy).	Within 1 week following inclusion
Other	Medical History questionnaire, part 3 (family history, COVID-19 info and medication use)	Family history of cardiovascular diseases in 1st-degree family members before age 60 years: sudden death <50 years (yes/no); myocardial infarction or cardiac arrest (yes/no); coronary stenting or coronary artery bypass grafting (yes/no); stroke [cerebral infarction or haemorrhage] (yes/no); high cholesterol (yes/no); dilation of an artery [aneurysm] (yes/no); narrowing of an artery [stenosis] (yes/no, if yes: which artery (carotid/coronary/legs/other).; COVID-19: had coronavirus infection (yes/no/probably, if yes or probably: date of infection (dd-mm-yyyy) and how the infection was diagnosed (PCR test/CT scan/antigen test/self-test/general practitioner or medical specialist diagnosed/I only have a suspicion that I had a coronavirus infection).; Medication use: participant uses medication regularly in the last year (yes/no, if yes: name of drug, dose (mg), frequency (doses/day), comments) Other: room for further comments regarding health in general	Within 1 week following inclusion
Other	Exercise History questionnaire, part 1 (exercise history, participation in endurance races and current training status)	Lifetime exercise history (if multiple sports: the following data will be collected per sport discipline): sport discipline; age started (years); age quit (years); frequency (days/week); frequency (months/year); average duration of a session (minutes).; Participation in endurance races (how often participated in the following races/events): Zevenheuvelenloop (n); half marathon (n); marathon (n); ultra marathon (n); Nijmegen Four Days Marches (n); Kennedy march [80 km] (n); cycling events =120 km (n); Alpe d'HuZes (n); triathlon sprint (n); triathlon quart or half (n); triathlon whole/Ironman (n); other endurance races.; Current endurance activities (if multiple sports: the following data will be collected per sport discipline): sport discipline; age started (years); age quit (years); frequency (days/week); frequency (months/year); average duration of a session (minutes).	Within 1 week following inclusion
Other	Exercise History questionnaire, part 2 (strength exercise)	Strength: participation in strength training (yes/no).; If yes: frequency (days/week) of strength training, further specified as: Per type of muscle-strengthening exercise (using weight machines/bodyweight exercises/resistance exercises/holistic exercises): frequency (days/week); duration (0/<10/10-20/21-30/31-40/41-50/51-60/>60 minutes); muscle groups trained (legs/hips/back/abdomen/chest/shoulders/arms). Intensity at which the abovementioned muscle-strengthening exercises will be performed (0-10, 0 being extremely light, 10 being extremely heavy).; Other: room for further comments regarding exercise history	Within 1 week following inclusion
Other	Other biomarker concentrations in blood	creatinine (µmol/L); eGFR (ml/min/1.73m2); total cholesterol (mmol/L), HDL cholesterol (mmol/L), LDL cholesterol (mmol/L), albumin (g/L), cardiac myosin binding protein C (ng/ml).; eGFR: estimated glomerular filtration rate; HDL: high-density lipoprotein; LDL: low-density lipoprotein;	At day of inclusion
Primary	High-sensitivity cardiac troponin I (hs-cTnI)	Concentrations of high-sensitivity cardiac troponin I (hs-cTnI) in plasma in ng/L	Within 5 days before exercise event, within 6 hours post-exercise cessation, 24-48 hours post-exercise cessation
Primary	High-sensitivity cardiac troponin T (hs-cTnT)	Concentrations of high-sensitivity cardiac troponin T (hs-cTnT) in plasma in ng/L	Within 5 days before exercise event, within 6 hours post-exercise cessation, 24-48 hours post-exercise cessation
Secondary	General CT scan data	CT scan date (dd-mm-yyyy); average heart rate during scan (bpm); total radiation dose (mSv); beta-blockers administration (yes/no, if yes: dose (mg)); nitro-glycerine administration (yes/no, if yes: dose (mg)); image quality (good/moderate/poor); FFR series obtained (yes/no, if yes: quality(good/moderate/poor)); incidental findings.	within 3 months after inclusion
Secondary	Coronary artery calcification score	Coronary artery calcium score [=CACS], per coronary artery or other (LM/LAD/LCX/RCA/RI/Aorta/Valves/Other) and total: lesion count (n); Agatston score (AU); volume (mm3); density (HU). Total CACS (AU); total volume (mm3); total density (HU); MESA percentile (%).; LM: left main; LAD: left anterior descending; LCX: left circumflex; RCA: right coronary artery; RI: ramus intermedius; AU: Agatston units; HU: Hounsfield units; MESA: Multi-Ethnic Study of Atherosclerosis.	within 3 months after inclusion
Secondary	Coronary stenosis and plaque characteristics	Coronary stenoses, per segment (1-18): maximum stenosis degree (0%/1-24%/25-49%/50-69%/70-99%/100%/non-diagnostic/vessel absent); number of calcified plaques (n); number of partially calcified plaques (n); number of non-calcified plaques (n).; Presence of myocardial bridging (yes/no); heart 'dominance' (PDA supplied by RCA/PDA supplied by LCX); room for general comments on CT scan.; In general, not per segment: stenosis involvement score (n); stenosis severity score (n); plaque burden (P0/P1/P2/P3/P4); high-risk plaque features, per type [low attenuation plaque/positive remodelling/spotty calcification/napkin ring sign] (yes/no); modifiers, per modifier [non-diagnostic/having =high-risk plaque features/ischemia/exceptions including coronary artery dissection, anomalous origin of the coronary arteries, coronary artery (pseudo) aneurysm, vasculitis, coronary artery fistula, extrinsic coronary artery compression, arterio-venous malformation, other causes] (yes/no); CAD-RADS 2.0 score.	within 3 months after inclusion
Secondary	Computed tomography derived Fractional Flow Reserve	CT-derived FFR per coronary artery (LM/LAD/LCX/RCA): FFR at the beginning of vessel (ratio); FFR at 1.5 mm diameter of vessel or most distal evaluable part (ratio); FFR at 20 mm distal from stenosis (ratio).; FFR signs for ischemia present [=FFR=0.75] (yes/no); borderline ischemia [=FFR 0.76-0.80] (yes/no), non-ischemia [=FFR >0.80] (yes/no).; FFR: fractional flow reserve	within 3 months after inclusion
Secondary	Incidence of mortality	Incidence of mortality (yes/no), if yes: date of death (dd-mm-yyyy) and cause of death; cardiovascular death (yes/no).	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
Secondary	Incidence of major adverse cardiovascular events	Incidence of MACE (yes/no), if yes: date, type of event (myocardial infarction/stroke/heart failure/revascularisation (both acute and elective)/sudden cardiac arrest), hospitalization (yes/no).; MACE: major adverse cardiovascular events.	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.