Mitochondria Preservation by Exercise Training: A Targeted Therapy for Cancer and Chemotherapy-induced Cachexia.
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 144
- 试验地点
- 1
- 主要终点
- Physical function
研究概览
简要总结
This study aims to define the contribution of cancer and chemotherapy to muscle and systemic alterations that drive the onset of cachexia in rectal cancer patients and validate in human cancer cachexia (CC) the alterations in mitochondrial function and neuromuscular junction (NMJ) observed in the experimental models, thus providing the rationale for potential anti-cachexia strategies based on exercise and or exercise mimetics.
详细描述
This is a multicenter observational prospective cohort study in rectal cancer patients after neoadjuvant therapy (ycTNM) stage II, III, and IV (AJCC 8th edit), clinically stratified in the pre-cachectic or cachectic stage according to Fearon K et al. definition. That will be subject to curative or palliative surgery through any surgical approach. And a control subgroup of patients who will undergo any abdominal surgery type through any approach type for no neoplastic or inflammatory disease.
The study will take place in four Italian centers of colorectal surgery.
Will be run a preoperatory physical performance, and will be recorded the physical activity by wearing a SmartWatch.
The quantity of muscle will be estimated by the cross-sectional area (CSA) or the skeletal muscle area (SMA) from the magnetic resonance imaging (MRI) or computed tomography CT, respectively, and the Skeletal muscle index (SMI). The muscular quality will be studied by the mean skeletal muscle radiation attenuation (SMRA) and MRI proton density fat fraction (PDFF). All these parameters will be calculated by a radiologist from the preoperative MRI or CT imaging study.
The study includes the analysis of preoperatory inflammatory and nutritional biomarkers. And a muscular biopsy harvested by the surgeon from the rectum or oblique abdominal during rectal resection-palliative surgery. The sample will undergo morphological and structural studies using histology, immunohistochemical, immunofluorescence, biochemical, and molecular analyses.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with confirmed histopathological diagnosis of rectal adenocarcinoma ycTNM stage II, III, or IV (AJCC 8th).
- •Patients treated with neoadjuvant therapy.
- •Patients that will be subject to curative intent or palliative surgery through any approach (open, laparoscopic, or robotic).
- •Ability to sign the informed consent.
排除标准
- •Rectal cancer stage I or any stage without neoadjuvant therapy.
- •Age < 18 and >75 years
- •Long steroid treatment for any cause.
- •Emergency setting.
- •Co-existent inflammatory bowel disease.
- •Inflammatory comorbidities (liver failure, diabetes, metabolic acidosis, acute and chronic renal failure, sepsis, AIDS, acute and chronic hepatitis, autoimmune disorders, and chronic obstructive pulmonary disease).
- •Healthy volunteers.
- •Other (simultaneous) neoplastic disease
结局指标
主要结局
Physical function
时间窗: Preoperative.
Determinate by the short physical performance battery (SPPB) Score, a series of tests used to evaluate lower extremity function and mobility in older people. Scores are assigned according to performance, with an overall maximum score of 12. A cut off score \< 10 indicates mobility disability and cut point: ≤ 8 points for diagnosing of severe sarcopenia
Muscle wasting- creatine kinase
时间窗: Preoperative.
Blood levels of creatine kinase (U/L).
Physical activity-Subjective Measurement
时间窗: Preoperative
Determinate by the physical activity scale for the elderly (PASE) Score, the overall score ranging from 0 to 793, higher scores indicated greater physical activity
Physical activity-Objective Measurement (step count)
时间窗: Preoperative.
Determinate by the average daily step count (total number of steps/14 days) recorded by wearing a Smart Watch for two weeks on consecutive days.
Physical activity-Objective Measurement (sleep)
时间窗: Preoperative.
Determinate by the average of daily sleep duration(total minutes of sleep/ 14 days) recorded by wearing a Smart Watch for two weeks on consecutive days.
Physical activity-Objective Measurement (sedentary time)
时间窗: Preoperative.
Determinate by the average daily sedentary time (total minutes of inactivity/14 days) recorded by wearing a Smart Watch for two weeks on consecutive days.
General health marker- hemoglobin
时间窗: Preoperative.
Blood levels of Hemoglobin (g/L).
Inflammatory status-White blood cells count
时间窗: Preoperative.
White blood cells count (10\^/L).
Morphometric analysis of skeletal muscle
时间窗: within 30 postoperative days.
Description of the dimension and type of muscular fibers from an abdominal wall muscle biopsy harvested intraoperatively.
Physical activity-Objective Measurement (active time)
时间窗: Preoperative.
Determinate by the average daily active time (total duration of activity in minutes/14 days) recorded by wearing a Smart Watch for two weeks on consecutive days.
Nutritional status - transferrin
时间窗: Preoperative.
Blood levels of transferrin(mg/dL).
Muscular quantity
时间窗: Preoperative.
Determinate by the Skeletal muscle index (SMI) = skeletal muscle area or cross-sectional area at L4-L5 (cm2)/height2(m2) from the preoperative magnetic resonance imaging.
Muscular quality (muscle fat content) by magnetic resonance imaging
时间窗: Preoperative.
Determinate by the proton density fat fraction (PDFF) of paraspinal muscles at L4-L5
Nutritional status - Prealbumin
时间窗: Preoperative.
Blood levels of prealbumin(mg/dL).
Molecular analysis of skeletal muscle
时间窗: within 60 postoperative days.
Characterization of molecular signatures associated with Neo-adjuvant Chemotherapy and rectal cancer by comparing molecular profiles of a muscular biopsies harvested intraoperatively.
Nutritional status - Albumin
时间窗: Preoperative.
Blood levels of albumin (g/dL).
Inflammatory status - C-reactive protein
时间窗: Preoperative.
Blood levels of C-reactive protein (mg/dL).
Muscle protein metabolism
时间窗: within 60 postoperative days.
Muscle-specific ubiquitin-ligases expression, mitophagy cargo shuttle, fusion-fission machinery, and mitochondrial biogenesis will be assayed from a muscular biopsy harvested intraoperatively.
次要结局
- Overall survival(3 years after surgery.)