Effects of Exercise Training on Systemic Inflammation an Muscle Repair According to the Chronic Obstructive Pulmonary Disease Phenotype
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Change from baseline in TNF-alpha and its receptors, muscle isoforms of IGF-1 and its receptor in samples of quadriceps muscle satellite cells at 3 moths.
研究概览
简要总结
AIM: To identify those mechanisms involved in the systemic and muscular response to exercise treatment, in two different Obstructive Chronic Pulmonary Disease (COPD) phenotypes (emphysema and non-emphysema). The investigators will evaluate the effect of exercise training, on exercise outcomes, peripheral muscle strength measures, dyspnea and quality of life indices, and markers of systemic inflammation and muscle repair.
SUBJECTS: The investigators will study 30 COPD patients in GOLD II-IV stages, with symptomatic disease. Patients will be differentiated into 2 different phenotypes: predominant-emphysema and non-predominant emphysema (15 subjects for each group), according to high resolution computed tomography (HRCT) scanning images, and after the specific analysis with the MeVisPulmo software. After patients are typified, they will be included in the 12- wk training programme. MEASURES(pre&post-training):Basic blood analysis, EKG, spirometry, blood gases, pletysmography, gas diffusion, maximal inspiratory and expiratory pressure (MIP,MEP), bioimpedanciometry, 1RM test and isometric strength determination, 6-min walking test (6MWT), maximal and submaximal cycle-ergometry, and dyspnea using the Mahler's Basal and Transitional Dyspnoea Indexes (BDI/TDI) and quality of life (Chronic Respiratory Disease Questionnaire [(CRDQ]) evaluation. Besides, the investigators will measure blood PCR and cytokines levels (IL6, IL8, IL10, IL12, TNF-α, IGF-1, and MIC-A & MIC-B). Muscle biopsies will be made (quadriceps) for detection of TNF-α, TNFR-I, TNFR-II, IGF-1Ea and MGF, IGF-1R, genes bound to biogenesis, markers of cell lesion-stress and myosin heavy chains (MyHC) type I and II, N-CAM/CD56 and Met & Desmin
详细描述
STUDY POPULATION: Patients diagnosed COPD using the criteria established by the ATS (American Thoracic Society) and the SEPAR (Spanish Society of Pneumology and Thoracic Surgery) obstruction presenting moderate to severe airway obstruction (FEV1 <60%) and a clinical impact of their disease. Patients should be stable and appropriate therapy, and must not have suffered exacerbations of the disease over a period of three months before the study, and without treatment with oral corticosteroids for at least the same period.
SAMPLE SIZE: 30 patients diagnosed at the Department of Pulmonology, Hospital Virgen del Rocío de Sevilla, informed consent.
Sample size calculation: Analyzing the effect size at the expense of an improvement in the work achieved over 15 W in the stress test, and considering a standard deviation of this parameter + / - 10W, allowing to detect differences in metabolic variables muscle, taking some risks alpha <0.05 and beta < 0, 2 and calculating a percentage of losses of 15%, the investigators estimate a sample size of 15 patients for each group (PC-size).
EXIT CRITERIA OF THE STUDY:
- patient's clinical decompensation
- Loss of 3 or 5 consecutive sessions of the training program discontinued.
- On the initiative of the patient
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 45 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •COPD patients diagnosed according to criteria established by the ATS (American Thoracic Society) and the SEPAR (Spanish Society of Pneumology and Thoracic Surgery) obstruction presenting moderate to severe airway obstruction (FEV1 <60%) and a clinical impact of their disease. Patients should be stable and appropriate therapy, and must not have suffered exacerbations of the disease over a period of three months before the study, and without treatment with oral corticosteroids for at least the same period.
排除标准
- •Other cardio-respiratory diseases, cardiovascular, neuromuscular or metabolic might interfere with the results.
- •Systemic diseases, alcohol intake (> 80 g / day) or treatment with drugs with potential effect on muscle structure
- •Inability or disagree to participate in an exercise program.
结局指标
主要结局
Change from baseline in TNF-alpha and its receptors, muscle isoforms of IGF-1 and its receptor in samples of quadriceps muscle satellite cells at 3 moths.
时间窗: Baseline and end of follow-up period of 3 moths
Compare these values according to the phenotype of the patient (airway-predominant vs. emphysema-predominant) and assess the effect of the training program, according to the phenotype, the regenerative potential and muscle remodeling.
次要结局
- Pax7, M-cadherin and Myo-D and its receptor in samples (molecules and repair-myogenesis) of quadriceps muscle satellite cells.(Baseline and end of follow-up period of 3 moths)
- MIC-A and MIC-B soluble in serum.(Baseline and end of follow-up period of 3 moths.)
- CRP, IL6, IL8, IL10, IL12, TNF alpha, IGF-1 (systemic inflammatory profile) in serum.(Baseline and end of follow-up period of 3 moths.)
研究者
Francisco Ortega Ruiz
Head of Section of Pneumology
Hospitales Universitarios Virgen del Rocío