Esophageal Cancer, Gastric Cancer (Diagnosis), Upper Gastrointestinal Cancer
Conditions
Keywords
upper gastrointestinal cancers, exercise, high-intensity interval training, randomized controlled trial, exercise oncology
Brief summary
This randomized controlled trial aims to determine the optimal exercise intensity for improving postoperative recovery in patients with upper gastrointestinal cancer. Participants who have undergone curative surgery will be randomly assigned to high-intensity interval training (HIIT), low-intensity continuous training (LICT), or usual care. The exercise interventions will be performed under supervision three times per week for eight weeks. The primary outcome is peak oxygen uptake (VO₂peak), assessed using cardiopulmonary exercise testing. Secondary outcomes include physical function, body composition, patient-reported outcomes, and biological and mechanistic markers such as inflammatory biomarkers, muscle-related factors, and gut microbiota. This study will also explore potential mechanisms underlying exercise-induced adaptations and their association with clinical outcomes.
Detailed description
This study is a single-center, three-arm randomized controlled trial designed to evaluate the effects of exercise intensity on postoperative recovery in patients with upper gastrointestinal cancer. Patients who have undergone curative surgery for esophageal or gastric cancer will be enrolled 6 ± 2 weeks after surgery and randomly assigned to high-intensity interval training (HIIT), low-intensity continuous training (LICT), or usual care. The exercise intervention consists of supervised aerobic and resistance training performed three times per week for eight weeks. HIIT involves repeated high-intensity intervals interspersed with recovery periods, whereas LICT consists of continuous low-intensity aerobic exercise. The primary outcome is the change in peak oxygen uptake (VO₂peak) from baseline to 8 weeks, assessed using cardiopulmonary exercise testing. Secondary outcomes include measures of physical function, skeletal muscle mass, physical activity, quality of life, and biological and mechanistic outcomes such as inflammatory biomarkers, muscle-related factors, and gut microbiome composition. This study aims to clarify the dose-response relationship of exercise intensity and to explore the physiological mechanisms underlying exercise-induced adaptations in the early postoperative phase.
Interventions
BEHAVIORALHigh-Intensity Interval Training (HIIT)
Supervised aerobic high-intensity interval training combined with resistance training and nutritional counseling. Aerobic training is performed on a cycle ergometer and consists of four sets of 4-minute high-intensity intervals at 80-95% of VO₂peak, interspersed with 3-minute recovery periods at 60% of VO₂peak. Each session includes a 3-minute warm-up and a 3-minute cool-down, with a total duration of 34 minutes. Training is performed three times per week for eight weeks. Resistance training includes chest press, leg extension, leg press, and abdominal exercises using pneumatic resistance machines, consisting of two sets of 20-25 repetitions at approximately 20RM. Nutritional counseling is provided by a registered dietitian once every four weeks for a total of two sessions during the intervention period.
BEHAVIORALLow-Intensity Continuous Training (LICT)
Supervised low-intensity continuous training combined with resistance training and nutritional counseling. Aerobic training is performed on a cycle ergometer at 37-45% of VO₂peak for 28 minutes per session, with a 3-minute warm-up and a 3-minute cool-down, for a total duration of 34 minutes. Training is performed three times per week for eight weeks. Resistance training is identical to the HIIT group and includes chest press, leg extension, leg press, and abdominal exercises using pneumatic resistance machines, consisting of two sets of 20-25 repetitions at approximately 20RM. Nutritional counseling is provided by a registered dietitian once every four weeks for a total of two sessions during the intervention period.
Sponsors
Kansai Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Diagnosed with esophageal or gastric cancer * Received curative surgery * 6 ± 2 weeks after surgery * Ability to provide written informed consent
Exclusion criteria
* Communication difficulties * Poor general status * Undergone combined laryngopharyngectomy * Unsuitable for evaluation or exercise intervention * Unsuitable for the study as determined by the primary physician
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak oxygen uptake (VO₂peak) | Baseline and 8 weeks after the intervention | Cardiorespiratory fitness will be assessed using symptom-limited cardiopulmonary exercise testing (CPET) on a cycle ergometer under medical supervision with continuous breath-by-breath gas analysis. After a 4-minute unloaded warm-up, workload is increased by 10-20 W/min depending on patient condition, with participants cycling at 50 rpm until volitional exhaustion. The test is terminated when cadence falls below 40 rpm, at physician discretion, or at patient exhaustion, followed by a 2-minute cool-down at 20 W. Continuous 12-lead ECG, blood pressure, and oxygen saturation are monitored during testing. VO₂peak is defined as the highest 30-second averaged oxygen uptake immediately prior to exhaustion. Peak workload, peak heart rate, and oxygen uptake at ventilatory threshold are also recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Handgrip strength | Baseline, 4 weeks, and 8 weeks after the intervention | Handgrip strength will be measured using a standard adjustable-handle dynamometer (InGrip, InBody Japan Inc., Tokyo, Japan). Measurements will be performed in a standing position with arms at the side. Two maximal voluntary efforts will be recorded for each hand, and the highest value will be used (kg) as the outcome measure. |
| Chair stand test | Baseline, 4 weeks, and 8 weeks after the intervention | Lower-limb muscle strength will be assessed using the 30-second chair stand test (CS-30). Participants will perform as many sit-to-stand repetitions as possible within 30 seconds without using their hands from a standard chair (approximately 43 cm seat height). The total number of completed stands will be recorded. Extended versions (CS-60 and CS-90) will be derived as endurance indicators. |
| Short Physical Performance Battery (SPPB) | Baseline, 4 weeks, and 8 weeks after the intervention | Physical performance will be assessed using the SPPB, consisting of standing balance, gait speed, and chair stand tests. Each component is scored and summed to produce a total score ranging from 0 (worst performance) to 12 (best performance). |
| Skeletal muscle mass | Baseline, 4 weeks, and 8 weeks after the intervention | Skeletal muscle mass will be measured using a segmental multi-frequency bioelectrical impedance analyzer (InBody770, InBody Japan Inc., Tokyo, Japan). |
| Physical activity (Japanese version of the International Physical Activity Questionnaire-Short Form) | Baseline, 4 weeks, and 8 weeks after the intervention | Physical activity will be assessed using the Japanese version of the International Physical Activity Questionnaire-Short Form (IPAQ-SF). The IPAQ-SF provides an estimate of total physical activity expressed in metabolic equivalent task minutes per week (MET-min/week), calculated based on walking, moderate, and vigorous physical activities. The total score ranges from 0 to theoretically unlimited values, with higher scores indicating greater levels of physical activity. |
| Total exercise volume | During the 8-week intervention period | Total exercise volume will be calculated as the cumulative prescribed aerobic and resistance exercise over the 8-week intervention period. Aerobic exercise volume will be based on prescribed duration and intensity (HIIT or LICT protocols). Resistance training volume will be calculated by taking into account both the number of sets and repetitions performed across all prescribed exercises during the intervention period. |
| Exercise adherence | During the 8-week intervention period | Exercise adherence will be defined as the proportion of completed supervised exercise sessions and compliance with the prescribed exercise protocol, expressed as a percentage. |
| Patient-reported outcomes | Baseline, 4 weeks, and 8 weeks after the intervention | Health-related quality of life and symptoms will be assessed using the EORTC QLQ-C30. Scores for functional scales, symptom scales, and global health status will be linearly transformed to a 0-100 scale. |
| Blood biomarkers | Baseline, 4 weeks, and 8 weeks after the intervention | Serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), irisin, SPARC, and adrenaline will be measured. |
| Gut microbiome | Baseline and 8 weeks after the intervention | Gut microbiome composition will be analyzed using 16S rRNA sequencing of stool samples to assess alpha diversity, beta diversity, and taxonomic composition. |
| Urinary urea nitrogen | Baseline, 4 weeks, and 8 weeks after the intervention | Urinary urea nitrogen (UUN) as an indicator of protein metabolism and nutritional status. |
| Adverse events | During the 8-week intervention period | All adverse events will be systematically recorded throughout the study period. |
| Pneumonia | During the 8-week intervention period | Pneumonia will be defined as new or progressive infiltrates on chest radiographs or CT scans, as well as meeting at least two of the following three criteria: body temperature greater than 38°C, leukopenia or leukocytosis (white blood cell count less than 4 × 10⁹/L or greater than 10 × 10⁹/L), and purulent sputum. |
| Readmission | During the 8-week intervention period | Unplanned hospital readmission will be defined as any admission occurring after discharge and within the study period, extracted from medical records. |
Countries
Japan
Contacts
CONTACTTakuya Fukushima
CONTACTJiro Nakano
PRINCIPAL_INVESTIGATORTakuya Fukushima
Kansai Medical University
Outcome results
None listed