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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Serum butyrate concentrations
研究概览
简要总结
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:
- 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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
- •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.
研究组 & 干预措施
Control group
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.
干预措施: Supplement (Dietary Supplement)
Moderate load training group
The moderate load training group will enroll in eight weeks of supervised moderate load cycling training.
干预措施: Moderate load exercise training (Behavioral)
High load training group
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.
干预措施: High load exercise training (Behavioral)
结局指标
主要结局
Serum butyrate concentrations
时间窗: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
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.
Fecal butyrate concentrations
时间窗: At baseline (T1), mid-intervention after four intervention weeks (T2), post-intervention after eight intervention weeks (T3), and 10 days following intervention completion (T4).
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.
次要结局
- Short-chain fatty acids(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(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(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(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(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(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(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(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(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(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(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(Each training session, once every weekend, and at day 2 and day 3 of each experimental assessment period.)
- Heart rate variability(Each training session, once every weekend, and at day 2 and day 3 of each experimental assessment period.)
- Inflammatory status(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(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(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(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(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(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(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(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(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(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(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(During three days each week during the study and three days before and during the experimental assessment periods.)
- Muscle protein synthesis and breakdown(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(From baseline (T1) until 10 days following intervention completion (T4).)
- Number of participants classified as overreached(Post-intervention (T3, week 8))
研究者
Stefan De Smet
Professor doctor Stefan De Smet
KU Leuven