ExerciseICARUSNCT07481578
Impact of Training Load on the Gut miCrobiome And Its Relation to exeRcise Performance, mUscle Phenotype, and markerS of Overreaching in Healthy Men
A study testing Supplement, Moderate load exercise training and High load exercise training in people with Exercise and Overreaching, run by Stefan De Smet at 1 site in Belgium.
Trial summary
The goal of this study is to learn how different amounts of supervised indoor cycling training change gut health (gut bacteria, the substances gut bacteria make, and the gut barrier integrity), and how these changes relate to changes in fitness, muscle health, and signs of doing too much training (a state called… Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Exercise, Overreaching, Butyrate
- What is being tested?
- Supplement, Moderate load exercise training and High load exercise training
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteBelgium
- Study dates
- 7 Oct 2024to 31 May 2027
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Males between 18 and 45 years old.
- Recreationally active individuals, with a weekly exercise training volume between one and six hours per week.
- Good health status confirmed by a sport medical screening, which includes a sport medical questionnaire and resting electrocardiogram.
- Body Mass Index (BMI) between 18.5 and 27.5 kg/m².
- Masters the Dutch language.
Who cannot join
- Engagement in strenuous competitive sports one month prior to or during the study intervention.
- Medication and vaccination: Pro- or antibiotic treatment during the past three months, non-steroidal anti-inflammatory drugs (NSAIDs) or cholestyramine during the past month, drugs interfering with intestinal permeability (e.g., prokinetics, laxatives, lubiprostone, loperamide, anti-spasmodics, linaclotide, proton pump inhibitors) during the past month. Vaccinations within one month prior to or during the study intervention.
- Blood donations within three months or plasma donation within one month prior to or during the study intervention.
- Inflammatory bowel disease (Crohn or colitis ulcerosa) or celiac disease.
- Diagnosed irritable bowel syndrome.
- Intake of any performance-enhancing medication or nutritional supplements known to modulate the gut microbiome in the two months prior to or during the study.
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- Substance abuse, including alcohol consumption of more than three units/day (weekly average).
- Any injury or pathology considered a contraindication for performing physical exercise, as determined by the medical doctor overseeing the preparticipation medical screening.
- No access to smartphone and/or computer with internet access.
- No willingness to use the Polar Flow app and MijnEetmeter to collect physical activity, heart rate, sleep, and food intake data.
- Concomitant participation in another interventional trial, without approval from the research team.
- Any other reasons considered by the research team that the participant will not complete the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Belgium1 site, 1 recruiting
- Recruiting
Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Leuven, Belgium
Leuven, Vlaams Brabant, 3001
Stefan De Smet, +32 16 37 64 87, stefan.desmet@kuleuven.be
Sofie Engelborghs, +32495158699, sofie.engelborghs@kuleuven.be
About this study
Official title: ICARUS: Impact of Training Load on the Gut Microbiome and Its Relation to Exercise Performance, Muscle Phenotype, and Markers of Overreaching in Healthy Men: Phase A - Human Trial
The goal of this study is to learn how different amounts of supervised indoor cycling training change gut health (gut bacteria, the substances gut bacteria make, and the gut barrier integrity), and how these changes relate to changes in fitness, muscle health, and signs of doing too much training (a state called 'overreaching'). The study includes healthy, recreationally active men aged 18 to 45 years.
The primary questions, for which the study is powered (sufficient participants included), are:
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- Does moderate load training change blood and faecal levels of butyrate (a short-chain fatty acid made by gut bacteria) after eight weeks compared with a control group?
- Compared to moderate load training, do higher training loads lead to different responses in blood and faecal levels of butyrate?
Researchers will compare:
- A control group that does not complete structured training;
- A moderate-load training group that completes eight weeks of supervised cycling (4x/week);
- A high-load training group that completes four weeks of moderate-load training followed by four weeks of higher training load (twice the number of training sessions).
Participants will:
- Be randomly assigned to one of the three groups;
- Complete 8 weeks of supervised indoor cycling sessions if assigned to a training group;
- Complete four study assessment periods (baseline, after week four, after week eight, and after a short taper (rest period);
- Provide blood, stool, skeletal muscle, urine, saliva, and breath samples during the assessment periods;
- Complete fitness and performance tests and questionnaires during the assessment periods.
Read the detailed description
ICARUS is a monocentric, randomized, controlled, three-arm, parallel-group trial designed to determine whether exercise training load (moderate versus high) modulates the human gut ecosystem, with a primary focus on gut microbial short-chain fatty acid (SCFA) production, and to test whether interindividual gut responses relate to physiological adaptations and potential maladaptations (i.e., overreaching).
STUDY DESIGN: 45 healthy, recreationally active men will be randomized in a 1:1:1 allocation ratio to: (i) a non-training control group, (ii) a moderate-load cycling training group, or (iii) a high-load cycling training group. The intervention lasts 8 weeks and is followed by a 10-day taper period. Outcomes are assessed at four time points: baseline (T1), mid-intervention after 4 weeks (T2), post-intervention after 8 weeks (T3), and post-taper 10 days later (T4).
RANDOMIZATION: Randomization will be stratified by baseline habitual training volume (>3.5 hours versus ≤3.5 hours of exercise per week) using permuted blocks of varying size and a computer-generated allocation sequence. Allocation will be implemented using a secure REDCap web application to support allocation concealment from personnel involved in data collection and analysis.
SETTING AND RECRUITMENT: The trial is conducted at the Exercise and Muscle Physiology Research Group, Department of Movement Sciences, KU Leuven (Leuven, Belgium). Recruitment uses multiple channels, including email invitations, classroom announcements, posters/flyers, and social media.
FAMILIARIZATION AND STANDARDIZATION PROCEDURES: Approximately one week before the intervention starts, participants attend one familiarization session to minimize learning effects and standardize procedures across subsequent assessments. Familiarization includes key performance and physiological testing procedures and instruction on study devices and diaries. A personalized, standardized dietary plan is developed for the three days preceding each assessment period and the assessment days to improve within-participant dietary consistency across time points and to align with specific test requirements (e.g., fiber intake, carbohydrate loading, lactose/mannitol restriction where applicable).
INTERVENTION ARMS - CONTROL GROUP: Participants do not perform a structured training program. To control for expectancy effects, they receive a supervised weekly placebo capsule (1 g granulated sugar) presented as a 'novel plant extract' purported to support gut health and performance. Participants are asked to maintain their habitual exercise patterns and to monitor relevant behaviors as instructed.
INTERVENTION ARMS - MODERATE-LOAD TRAINING GROUP: Participants complete 8 weeks of supervised indoor cycling followed by a 10-day taper. Training is performed on an electromagnetically braked cycle trainer, supervised at the study center. The weekly structure comprises four sessions per week with a fixed sequence of session types (moderate-intensity continuous training, high-intensity interval training, moderate-intensity continuous training, and sprint interval training), and progressive load increases according to a standardized plan.
INTERVENTION ARMS - HIGH-LOAD TRAINING GROUP: Participants complete 4 weeks identical to moderate-load training group, followed by 4 weeks of high-load training in which training volume is doubled relative to MOD by increasing session frequency while maintaining the same intensity distribution.
EXERCISE INTENSITY PRESCRIPTION: Training intensity is individualized using physiological thresholds derived from an incremental cardiopulmonary exercise test with lactate measurements, including power at the first lactate threshold, second lactate threshold, and maximal power output. Training is prescribed based on cycling power output.
ASSESSMENT PERIODS: Each of the four assessment periods spans three consecutive days of home-based and study center-based procedures under standardized conditions and at the same time of day for each participant to limit circadian variability. Assessments integrate biospecimen collection and multi-system phenotyping, including gut-related measures (e.g., SCFAs, gut barrier integrity testing), exercise performance tests, skeletal muscle phenotyping, cardiometabolic testing, autonomic measures, and self-report instruments relevant to recovery and psychological well-being. Stool samples are collected at home and stored frozen prior to transfer to the study center for biobanked storage.
BIOSPECIMEN HANDLING AND STORAGE: Biological samples including blood, stool, skeletal muscle, urine, and saliva are labeled using a study-specific identifier and stored at -20°C of -80°C until analysis and/or future use in accordance with institutional biobank requirements and applicable regulations.
BLINDING AND BIAS MITIGATION: Because of the behavioral nature of the intervention, participants cannot be blinded to group assignment. To reduce expectancy effects, the control group receives placebo supplementation presented as performance-relevant. Where feasible, outcome assessors and laboratory personnel remain blinded to group allocation during data collection and analyses, although some partial unblinding may occur due to staffing constraints.
SAMPLE SIZE AND STATISTICAL PRINCIPLES: The planned sample size is 45 participants (15 per arm), accounting for attrition, and is based on power considerations derived from prior evidence on fecal butyrate responsiveness to endurance training, given the absence of robust human data for the primary circulating SCFA endpoint at the time of planning. Analyses will follow intention-to-treat principles. Group differences over time will be estimated using constrained longitudinal data analysis models that jointly model baseline and follow-up measures while constraining baseline means to be equal across groups, thereby providing ANCOVA-equivalent estimands and accommodating missing data under a missing-at-random assumption via maximum likelihood. A hierarchical testing strategy is planned for the primary and key secondary endpoints to control the type I error rate. Sensitivity analyses may include per-protocol analyses defined prior to database lock.
- Conditions
- Exercise, Overreaching, Butyrate, Gut Microbiome, Exercise Performance, Skeletal Muscle
- Being tested
- Supplement, Moderate load exercise training, High load exercise training
- Keywords
- Exercise training, Training load, Overload training, Fecal butyrate, Gut health, Exercise performance, Muscle phenotype, Physical fitness, Overreaching, Glucometabolic health, Vascular health, Muscle adaptation, Heart Rate Variability (HRV), Anthropometrics, Metabolic health, Food intake
- Medical subject headings
- Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SupplementDietary supplement
Also called CON
The nature of the intervention does not allow blinding of study participants. However, to induce an 'expectancy-effect' in the control group, participants allocated to the control group will receive dietary placebo supplementation. Participants will be told (deceived) that this novel 'plant extract' is believed to have the potential to mimic training effects on gut health and exercise performance. The dietary placebo capsule will consist of 1 g sugar. Intake of the dietary placebo capsule will take place after a fasting state of six hours or more, at a fixed timepoint once a week, and under direct supervision of a research investigator (Sofie Engelborghs). The control group does not participate in any study-related training sessions, but will be asked to continue and monitor (Polar Pacer heart rate monitor) their normal physical activities and sports.
Moderate load exercise trainingBehavioural
Also called MOD
The moderate load training group will enroll in an exercise intervention of 8 weeks. This intervention consists of cycling sessions on an electromagnetically braked ergometer under direct supervision of the investigators at the Exercise and Muscle Physiology Group. Training intensities are prescribed based on the power output associated with the first and second lactate threshold and maximal power output obtained during a maximal incremental step test with capillary lactate measurements. Three types of training sessions will be prescribed: moderate-intensity continuous training (2x/week), high-intensity interval training (1x/week), and sprint interval training (1x/week). The training load will gradually increase over time, by increasing the session duration and/or intervals.
High load exercise trainingBehavioural
Also called HIGH
Participants allocated to the high load training group will conduct a similar intervention as the moderate load training group, but with double the amount of training sessions (8x/week) throughout the last four weeks of the 8-week training program. The four weeks of high load training aims to induce a state of overreaching in some though not all participants allocated to the high load training group.
| Study group | Role | What they receive |
|---|---|---|
| Control group | Placebo comparator | Participants allocated to the control group do not perform a structured training program. To control for expectancy effects, they receive a supervised weekly placebo capsule (1 g granulated sugar) presented as a 'novel plant extract' purported to support gut health and performance. Participants are asked to maintain their habitual exercise and dietary intake patterns and to monitor relevant behaviors as instructed. Receives: Dietary Supplement: Supplement |
| Moderate load training group | Experimental | The moderate load training group will enroll in eight weeks of supervised moderate load cycling training. Receives: Behavioral: Moderate load exercise training |
| High load training group | Experimental | The high load training group will enroll in four weeks of supervised moderate load cycling training followed by four weeks of supervised high load cycling training. Receives: Behavioral: High load exercise training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum butyrate concentrations
Diet and in particular fiber intake will be standardized for three days prior to and during the assessment days during which venous blood sample collection will take place. To promote microbial SCFAs production, participants will consume 15 g of oligofructose five hours prior to venous blood sample collection. Serum butyrate concentration will be assessed using gas chromatography-mass spectrometry.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Fecal butyrate concentrations
Diet and in particular fiber intake will be standardized for three days prior to and during the assessment days during which fecal collection will take place. Participants will be asked to collect a stool sample at the first experiment assessment day. Fecal butyrate concentration will be assessed using gas chromatography with flame ionization detection.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Secondary outcomes (28)
Short-chain fatty acids
Short-chain fatty acid concentration (i.e. acetate, propionate, and butyrate concentrations) will be assessed in serum (gas chromatography-mass spectrometry) and feces (gas chromatography with flame ionization detection).
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Gut microbiome
The gut microbiome will be evaluated using taxonomic composition and functional genetic capacity (shotgun metagenomics, feces).
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Gut barrier
Indices of gut barrier integrity will be assessed by lactulose mannitol ratio test (HPLC-ELSD) and plasma lipopolysaccharide binding protein (ELISA).
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Self-reported stool consistency, bowel movement frequency, and gastrointestinal distress
A gastrointestinal questionnaire will be used to report stool consistency, bowel movement frequency, and gastrointestinal distress.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Aerobic exercise performance
Aerobic exercise performance will be measured on a bicycle ergometer through a 30-min simulated time-trial test.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Anaerobic exercise performance
Anaerobic exercise performance will be measured on a bicycle ergometer through a 6-s isokinetic sprint test, and a 30-s isokinetic sprint test.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Cardiorespiratory fitness
Cardiorespiratory fitness will be evaluated through an incremental maximal cardiopulmonary exercise test (step test), throughout which peak oxygen uptake and the first and second lactate thresholds will be determined
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Knee extensor strength
Knee extensor strength will be assessed using a custom-build dynamometer.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Muscle fiber type composition
Muscle fiber type composition will be visualized and quantified using fluorescent immunohistochemical staining.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Muscular mitochondrial content, biogenesis, and remodelling
Markers of mitochondrial content, biogenesis, and remodelling will be quantified using a hierarchical analytical workflow combining western blotting, enzyme histochemistry, and spectrophotometric assays.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Glucose tolerance and insulin sensitivity in skeletal muscle
If the oral glucose tolerance test indicates between-group differences in glucose tolerance or insulin sensitivity, skeletal muscle samples will undergo western blot analysis to quantify key insulin-signalling proteins.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Heart rate
Heart rate will be measured using a Polar Pacer monitor connected to a Polar H10 chest strap. Resting heart rate will be assessed once weekly, while submaximal and maximal heart rate will be continuously recorded during all training and testing sessions.
Measured: Each training session, once every weekend, and at day 2 and day 3 of each experimental assessment period.
Heart rate variability
Heart rate variability (HRV) will be measured using a Polar Pacer monitor connected to a Polar H10 chest strap. RR intervals for HRV will be collected once weekly and during each experimental assessment timepoint, with measurements performed immediately upon waking in a supine position. HRV will be quantified using Kubios software, including time-domain, frequency-domain, and non-linear indices.
Measured: Each training session, once every weekend, and at day 2 and day 3 of each experimental assessment period.
Inflammatory status
Changes in serum hsCRP will be evaluated as marker of systemic low-grade inflammation. Gut-local inflammation will be assessed via fecal calprotectin.
In case differential inflammatory or maladaptive responses are observed between study arms, a predefined subset of stored biosamples will be subjected to more detailed inflammatory and gut-barrier profiling within available resources. If moderate vs high load training induces distinct changes in intestinal or systemic inflammatory status, gene and protein expression levels of muscle pro- and anti-inflammatory cytokines will be analyzed using commercially available ELISAs
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Hormonal status
Concentrations of resting and exercise-induced hormones related to the hypothalamic-pituitary-adrenal (HPA) axis, stress, energy regulation, and cortisol will be analyzed in venous blood and saliva samples using electrochemiluminescence immunoassay (ECLIA) or enzyme-linked immunosorbent assay (ELISA).
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Self-reported recovery-stress state
Participants will complete the validated Recovery-Stress Questionnaire for Athletes (RESTQ-Sport) to assess perceived recovery-stress balance. The RESTQ-Sport comprises 77 items across 19 scales. Each item is rated on a 7-point Likert scale (0 = "never" to 6 = "always"). The recovery-stress balance will be calculated by subtracting the total stress score (sum of 10 stress subscales) from the total recovery score (sum of 9 recovery subscales), with higher values indicating more favourable recovery states.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Self-reported mood disturbances
Mood disturbance will be assessed using the validated Profile of Mood States (POMS) questionnaire (McNair et al., 1971). The POMS is a 65-item instrument that evaluates transient, fluctuating mood states. It comprises six subscales: five negative affect dimensions (Fatigue, Depression, Tension, Anger, and Confusion) and one positive affect dimension (Vigour). Participants rate how they have felt during the past week on a 5-point Likert scale (0 = "not at all" to 4 = "extremely"). The total mood disturbance (TMD) score will be calculated by summing the five negative subscales and subtracting the positive (Vigour) subscale, with higher TMD values indicating greater overall mood disturbance.
An energy index will be calculated as the difference between the POMS Vigour and Fatigue subscale scores, providing an indicator of perceived energy and readiness to perform.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Self-reported physical and mental work load
Subjective workload will be assessed using the validated NASA Task Load Index (NASA-TLX) questionnaire, a reliable indicator of both physical and mental workload (Sandra \& Lowell, 1988). The NASA-TLX comprises six dimensions: Mental Demand, Physical Demand, Temporal Demand, Frustration, Effort, and Performance. Participants will rate each dimension on a 20-point scale ranging from "very low" to "very high." The overall workload score will be calculated as the mean of the six dimension ratings, with higher scores indicating greater perceived workload.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Self-reported physical and mental well-being
Subjective well-being will be assessed using the Wellness Questionnaire (Bellinger, 2020), which comprises seven items evaluating physical and mental well-being. Participants will rate each item on a 1-10 Likert scale, where higher scores indicate better perceived well-being. The questionnaire will be completed at the end of each intervention week and at each experimental assessment period. An overall well-being score will be calculated as the sum of all item scores.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Self-reported symptoms of upper respiratory tract infections
The Wisconsin Upper Respiratory Symptom Survey (WURSS-21) will be used to monitor the incidence and severity of upper respiratory tract infections (Barrett et al., 2009). Participants will rate one global question, ten symptom-related questions, and nine functional-impairment questions (e.g., ability to think, sleep, breathe, walk) on a 0-7 Likert scale (0 = no symptoms, 1 = very mild, 3 = mild, 5 = moderate, 7 = severe), based on average symptom intensity over the previous seven days. The total WURSS-21 score will be calculated as the sum of all items, with a score ≥ 21 indicating the incidence of an upper respiratory tract infection (URTI).
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Vascular health
Peripheral microvascular function will be assessed using a vascular occlusion test combined with near-infrared spectroscopy on the gastrocnemius muscle. The protocol will consist of a 2-min baseline recording, 8 min of arterial occlusion, and 5 min of reperfusion. Muscle oxygen extraction will be quantified from the StO₂ decline during occlusion, and microvascular reperfusion capacity will be determined from the rate of StO₂ recovery after cuff release.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
HOMA-IR
A venous blood sample will be collected after an overnight fast to analyze fasting glucose and insulin concentrations. Fasting glucose levels and the homeostasis model assessment of insulin resistance (HOMA-IR) will serve as indicators of liver insulin resistance.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Matsuda index
The Matsuda index, derived from an oral glucose tolerance test, will be used as a marker for muscle and whole-body insulin resistance. In this test, 75 g of glucose will be administered following a 10-12 hour overnight fast, and venous glucose and insulin levels will be measured at 0, 30, 60, 90, and 120 minutes post-administration.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Body composition
Body composition will be measured by a Dual Energy X-ray Absorptiometry (DXA) scan.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Food intake
Diet and nutritional intake will be monitored using a food diary (MijnEetmeter) during three days each week. Additionally, participants will follow a standardized dietary protocol for three days before and during the experimental assessment periods.
Measured: During three days each week during the study and three days before and during the experimental assessment periods.
Muscle protein synthesis and breakdown
If DXA reveals between-group changes in whole-body or regional fat-free mass, western blotting will be used to assess regulators of muscle protein synthesis and breakdown.
Measured: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
Intervention adherence and training monitoring
Adherence and fidelity to the training intervention will be assessed by recording the number of completed sessions, and the sessions' power output, heart rate, and session duration. Adherence to the dietary supplementation in the control group will be ensured via directly observed administration.
Continuation of participants' habitual sport activities outside the intervention will be monitored using the Polar Pacer smartwatch.
Measured: From baseline (T1) until 10 days following intervention completion (T4).
Number of participants classified as overreached
Participants in the high-load training group will be classified at T3 as overreached when both of the following are present relative to T2: (i) a reduction in exercise performance, defined as a lower mean power output during either the 30-second sprint test or the 30-minute time trial, and (ii) a reduction in the energy index calculated from the POMS questionnaire as Vigour minus Fatigue. To account for day-to-day variability, the reduction in exercise performance must exceed the coefficient of variation derived from the control group, and the reduction in energy index must exceed the standard error of measurement of the change score derived from the control group. Participants showing a reduction in energy index without a decrement in exercise performance will be classified as acutely fatigued.
Measured: Post-intervention (T3, week 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2026
- Study start7 Oct 2024
- Primary completion31 May 2027 (estimated)
- Study completion31 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ExerciseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants (n = 45) will be randomized in a 1:1:1 ratio to (i) eight weeks of dietary placebo supplementation followed by 10 days without placebo supplementation (CON; n = 15), (ii) eight weeks of moderate load cycling training proceeded by 10-day taper period (MOD; n = 15), or four weeks of moderate plus four weeks of high load (overload) cycling training proceeded by 10-day taper period (HIGH; n = 15). Participants will be randomized using a computer-generated randomization sequence uploaded to a secure web application (REDCap) which conceals the randomization sequence for all researchers.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stefan De Smet
- Sponsor type
- University, hospital or other
- Collaborators
- KU Leuven, Universiteit Antwerpen
- Responsible party
- Sponsor-investigator, Stefan De Smet, KU Leuven
- Investigators
- Stefan De Smet, Professor, Principal investigator, Exercise and Muscle Physiology Research Group, Department of Movement Sciences, KU Leuven, Leuven, Belgium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07481578
- Sponsor's protocol ID
- B3222024001516
- Other IDs
- 1172825N
- Acronym
- ICARUS
- Status last verified
- Mar 2026
- First submitted
- 4 Feb 2026
- Last updated
- 19 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: There is currently no final decision regarding sharing of de-identified individual participant data collected in this study. Any future data sharing will depend on participant consent, ethics approval, institutional requirements, and data protection considerations.