Multi-level Molecular Profiling of Peak Performance in Endurance Sports

Healthy Clinical Trial

— MSSA  

Official title:

A Pilot-study on Multi-level Molecular Profiling of Peak Performance in Endurance Sports

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05359744
• Other study ID #: jestep032022
• Status: Recruiting
• Phase: N/A
• Start date: October 15, 2021
• Est. completion date: October 15, 2022

Study information

• Verified date: April 2022
• Source: Paracelsus Medical University
• Contact: Jens Stepan, MD, PhD
• Phone: +43(0)5725555625
• Email: j.stepan[@]salk.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Physical activity triggers complex molecular responses, including changes in immune-, stress-, and metabolic pathways. For example, autophagy is essential for energy and cellular homeostasis through protein catabolism, and dysregulation results in compromised proteostasis, reduced exercise performance, and excessive secretion of signaling molecules and inflammatory proteins. However, previous research has been limited by the extend of molecules measured and biological processes covered. A better understanding of these processes through multi-omic analysis can improve knowledge of molecular changes in response to exercise. The main purpose of the investigators study is to analyze the effects of acute exercise in correlation to autophagy and other signaling cascades. Specifically, the investigators plan to perform multi-level molecular profiling in a cohort of healthy male elite cyclists and male and female recreational athletes, before, during, and after a bicycle ergometer test. The results will be compared to a control cohort without intervention.

Description:

This is a non-randomized controlled trial performed at the Paracelsus Medical University, Salzburg, Austria. The study will recruit 80 healthy men and women. Subjects who meet the inclusion criteria will be allocated to four arms (n = 20 in all groups): 1. elite cyclists, 2. male recreational athletes, 3. female recreational athletes, 4. male control group. After overnight fasting and medical check-up, groups 1-3 will undergo a bicycle ergometer-based exercise protocol designed to span low (aerobic) to severe (anaerobic) domains of exercise. The protocol consists of a 15 min aerobic warm-up phase followed by a ramp-bicycle ergometer protocol. During exercise, performance-relevant data will be continuously monitored. Venous blood specimens will be collected before exercise (baseline), at the end of the warm-up as well as 2 min, 10 min, and 30 min in recovery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: October 15, 2022
• Est. primary completion date: October 15, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• All arms: ability to give written informed consent
• Arms 1- 3: inconspicuous medical examination (medical history, resting ECG, echocardiography)
• Elite athletes (arm1, cyclists): maximum oxygen uptake > 65 ml/kg/KG
• Elite athletes (arm1, cyclists): participation in cycling competitions on a regular basis
• Recreational athletes (arms 2 and 3): maximum oxygen uptake < 65 ml/kg/KG for male subjects and < 55 ml/kg/KG for female subjects

Exclusion Criteria:

• All arms: unable to communicate adequately by language
• All arms: regular use of prescription drugs other than thyroxine or antihistamines
• All arms: alcohol consumption as equivalent doses averaging more than 40 g of pure alcohol per day
• All arms: use of illicit drugs
• All arms: known diseases of the cardiovascular system
• All arms: arterial hypertension over 160/90 mmHg at rest
• All arms: known pulmonary diseases, especially bronchial asthma
• All arms: surgery less than 4-6 months ago.
• All arms: abnormalities in the medical examination (medical history, resting ECG, echocardiography)
• Arms 1-3: orthopaedic diseases that preclude maximum exercise on a bicycle ergometer
• Elite athletes (arm1, cyclists): maximum oxygen uptake < 65 ml/kg/KG
• Recreational athletes (arms 2 and 3): maximum oxygen uptake > 65 ml/kg/KG for male subjects and > 55 ml/kg/KG for female subjects
• Arm 3: positive urine ß-HCG

Related Conditions & MeSH terms

• Exercise
• Exercise Test
• Healthy
• Physical Fitness

Intervention

Diagnostic Test:
• Performance testing
Performance testing on a bicycle ergometer.

Locations

Country	Name	City	State
Austria	Paracelsus Medical University	Salzburg

Sponsors (2)

Lead Sponsor	Collaborator
Paracelsus Medical University	Department of Psychiatry University of Bonn

Country where clinical trial is conducted

Austria, 

References & Publications (7)

Contrepois K, Wu S, Moneghetti KJ, Hornburg D, Ahadi S, Tsai MS, Metwally AA, Wei E, Lee-McMullen B, Quijada JV, Chen S, Christle JW, Ellenberger M, Balliu B, Taylor S, Durrant MG, Knowles DA, Choudhry H, Ashland M, Bahmani A, Enslen B, Amsallem M, Kobaya — View Citation

De Pauw K, Roelands B, Cheung SS, de Geus B, Rietjens G, Meeusen R. Guidelines to classify subject groups in sport-science research. Int J Sports Physiol Perform. 2013 Mar;8(2):111-22. Review. — View Citation

Hasin Y, Seldin M, Lusis A. Multi-omics approaches to disease. Genome Biol. 2017 May 5;18(1):83. doi: 10.1186/s13059-017-1215-1. Review. — View Citation

Hoffman NJ. Omics and Exercise: Global Approaches for Mapping Exercise Biological Networks. Cold Spring Harb Perspect Med. 2017 Oct 3;7(10). pii: a029884. doi: 10.1101/cshperspect.a029884. Review. — View Citation

Martin DT, McLean B, Trewin C, Lee H, Victor J, Hahn AG. Physiological characteristics of nationally competitive female road cyclists and demands of competition. Sports Med. 2001;31(7):469-77. Review. — View Citation

Mukherjee K, Edgett BA, Burrows HW, Castro C, Griffin JL, Schwertani AG, Gurd BJ, Funk CD. Whole blood transcriptomics and urinary metabolomics to define adaptive biochemical pathways of high-intensity exercise in 50-60 year old masters athletes. PLoS One — View Citation

Nicora G, Vitali F, Dagliati A, Geifman N, Bellazzi R. Integrated Multi-Omics Analyses in Oncology: A Review of Machine Learning Methods and Tools. Front Oncol. 2020 Jun 30;10:1030. doi: 10.3389/fonc.2020.01030. eCollection 2020. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proteomics and autophagy processes	Change in protein levels of autophagy biomarkers (LC3II & p62) of isolated PBMCs (peripheral blood mononuclear cells) by Western Blotting.	Before the exercise test (baseline), at the end of the 15 minute warm-up phase and 2 minutes, 10 minutes and 30 minutes after termination of the exercise test.
Secondary	Salivary cortisol levels	Salivary cortisol levels in nmol per Liter (nmol/L) after will be evaluated and compared to the control group	Before the exercise test (baseline), at the end of the 15 minute warm-up phase and 2 minutes, 10 minutes and 30 minutes after termination of the exercise test.
Secondary	Proteome patterns	Change in protein levels and protein phosphorylation by untargeted mass spectrometry-based proteomics and phosphoproteomics of isolated PBMCs (peripheral blood mononuclear cells).	Before the exercise test (baseline), at the end of the 15 minute warm-up phase and 2 minutes, 10 minutes and 30 minutes after termination of the exercise test.
Secondary	Metabolic processes	Targeted and quantitative analysis by mass spectrometry of change in metabolites of Plasma.	Before the exercise test (baseline), at the end of the 15 minute warm-up phase and 2 minutes, 10 minutes and 30 minutes after termination of the exercise test.
Secondary	Lipid profiling	Targeted and quantitative analysis by mass spectrometry of change in plasma Lipids.	Before the exercise test (baseline), at the end of the 15 minute warm-up phase and 2 minutes, 10 minutes and 30 minutes after termination of the exercise test.
Secondary	Phosphoproteome patterns	Change in protein phosphorylation by untargeted mass spectrometry-based phosphoproteomics of isolated PBMCs (peripheral blood mononuclear cells).	Before the exercise test (baseline), at the end of the 15 minute warm-up phase and 2 minutes, 10 minutes and 30 minutes after termination of the exercise test.
Secondary	Ubiquitinome patterns	Change in protein ubiquitination levels by untargeted mass spectrometry-based proteomics of isolated PBMCs (peripheral blood mononuclear cells).	Before the exercise test (baseline), at the end of the 15 minute warm-up phase and 2 minutes, 10 minutes and 30 minutes after termination of the exercise test.
Secondary	Epigenetic patterns	Evaluate epigentic methylation patterns through blood based epigenome analysis	Before the exercise test (baseline), at the end of the 15 minute warm-up phase and 2 minutes, 10 minutes and 30 minutes after termination of the exercise test.
Secondary	Exosomal protein patterns	Evaluate exosomal protein content through mass spectrometry based analysis	Before the exercise test (baseline), at the end of the 15 minute warm-up phase and 2 minutes, 10 minutes and 30 minutes after termination of the exercise test.