Multifactorial Intervention of Primary Prevention in High Risk Subjects: a Randomized Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 2,000
- 试验地点
- 1
- 主要终点
- Change in chronic inflammatory status
研究概览
简要总结
This prospective randomized pilot trial will evaluate a multiple intervention program of prevention in lifelong smokers aiming at reduction of chronic inflammation status through treatment with low-dose acetylsalicylic acid (ASA), smoking cessation with cytisine, targeted modification of diet and physical activity, in addition to early diagnosis with annual ultra low-dose spiral computed tomography (LDCT).
详细描述
The most recent population-based studies carried out in Europe and the US on hundreds of thousands of individuals have unequivocally identified three principal causes of mortality, morbidity and chronic disability: tobacco smoke, inadequate diet, and reduced physical activity. These risk factors are in large part reversible, because in heavy smokers, even after 60 years of age, cessation is associated with a clear reduction in all-cause mortality. The finding that lifestyle and eating habits are associated with the development of cancer has been confirmed in many studies: smoking, a sedentary lifestyle, excess red meat, processed foods and sugars are associated with increased risk, while an active lifestyle, non-exposure to smoke (both active and passive), consumption of whole grains, legumes and vegetables are associated with protection or a reduced incidence in at-risk subjects.
What is clear, and confirmed by many studies, is that cancer occurs more often in overweight individuals, and that cancer patients who are overweight have more difficulty treating their disease. Elevated plasma levels of C-reactive protein (CRP), even when still within normal limits, are the reflection of a chronic state of inflammation and are associated with poor prognosis in several tobacco-related diseases. CRP measurement is besides a simple test to predict the risk of heart attack and stroke as well as mortality from all causes and from cardiovascular disease. In a systematic review on adult solid tumors, elevated CRP levels were associated with higher mortality and recurrence rates, and this observation was confirmed in early-stage lung cancer by a recent meta-analysis. In patients with chronic obstructive pulmonary disease (COPD), high CRP is a strong and independent predictor of future morbidity and mortality, and an increase in CRP concurrent with a reduction of the forced expiratory volume in 1 second (FEV1) shows an even stronger effect on patient's outcome.
High levels of CRP are associated with poor prognosis in cancers of the upper aerodigestive tract, rhinopharynx, lung and urinary tract. From a dietary point of view, consumption of saturated fats has been directly associated with an increase in inflammatory status as measured by high levels of CRP, just like consumption of meat, while an inverse correlation with consumption of vegetables has been observed. For example, low levels of inflammatory factors have been found in individuals adhering to a Mediterranean diet. Another recurrent finding, at least for cancer, is the importance of daily physical activity, such as brisk walking for 30 minutes. Moreover, regular physical activity is associated with better prognosis and increased survival in patients with a cancer diagnosis.
The number of heavy smokers that will participate in early-diagnosis programs using spiral CT will undoubtedly increase in the future as a result of awareness campaigns, and the participating volunteers represent an excellent opportunity to evaluate the efficacy of targeted primary prevention programs.
The present program will combine several interventions according to the randomization arm, proposed in combination or in single treatment, including treatment with cytisine, reduction of chronic inflammation by treatment with low-dose aspirin (ASA), targeted modification of diet and physical activity, in addition to early diagnosis with annual ultra low-dose spiral computed tomography (LDCT).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 55 and 75 years
- •High consumption of cigarettes (≥ 30 packs/year)
- •Elegibility to annual LDCT screening
- •Confidence in Internet use
- •Absence of tumors for at least 5 years
- •Signed informed consent form
排除标准
- •Hypersensitivity to acetylsalicylic acid, salicylates or any of the excipients (excipients: cellulose powder, corn starch, coating: copolymers of methacrylic acid, sodium lauryl sulfate, polysorbate 80, talc, triethyl citrate)
- •Chronic treatment with acetylsalicylic acid, or other anti-clotting or anti-coagulant drugs (for example: heparin, dicumarol)
- •Treatment with methotrexate
- •Existing Mastocytosis
- •History of asthma induced by the administration of salicylates or substances to similar activity, particularly non-steroidal anti-inflammatory drugs
- •Gastroduodenal ulcer
- •Hemorrhagic diathesis
- •Severe chronic pathology (eg: severe respiratory and / or renal and / or hepatic and / or cardiac insufficiency)
- •Serious psychiatric problems
- •Previous treatment with Cytisine
- •Abuse of alcohol or other substances (even previous)
研究组 & 干预措施
Smoking cessation and Antinflammatory
Smoking cessation through the administration of Cytisine (in standard and prolonged administration) + reduction of inflammatory status through the administration of Acetylsalicylic acid, diet modification and physical activity increase + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: Cytisine (Drug)
Smoking cessation and Antinflammatory
Smoking cessation through the administration of Cytisine (in standard and prolonged administration) + reduction of inflammatory status through the administration of Acetylsalicylic acid, diet modification and physical activity increase + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: Acetylsalicylic acid (Drug)
Smoking cessation and Antinflammatory
Smoking cessation through the administration of Cytisine (in standard and prolonged administration) + reduction of inflammatory status through the administration of Acetylsalicylic acid, diet modification and physical activity increase + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: Diet Modification and Physical Activity Increase (Other)
Smoking cessation and Antinflammatory
Smoking cessation through the administration of Cytisine (in standard and prolonged administration) + reduction of inflammatory status through the administration of Acetylsalicylic acid, diet modification and physical activity increase + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: early lung cancer detection (Diagnostic Test)
Smoking cessation and Antinflammatory
Smoking cessation through the administration of Cytisine (in standard and prolonged administration) + reduction of inflammatory status through the administration of Acetylsalicylic acid, diet modification and physical activity increase + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: spirometry with CO test (Diagnostic Test)
Smoking cessation and Antinflammatory
Smoking cessation through the administration of Cytisine (in standard and prolonged administration) + reduction of inflammatory status through the administration of Acetylsalicylic acid, diet modification and physical activity increase + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: anthropometic data collection (Other)
Smoking cessation and Antinflammatory
Smoking cessation through the administration of Cytisine (in standard and prolonged administration) + reduction of inflammatory status through the administration of Acetylsalicylic acid, diet modification and physical activity increase + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: blood test (Other)
Smoking cessation
Smoking cessation through the administration of Cytisine (in standard and prolonged administration) + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: Cytisine (Drug)
Smoking cessation
Smoking cessation through the administration of Cytisine (in standard and prolonged administration) + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: early lung cancer detection (Diagnostic Test)
Smoking cessation
Smoking cessation through the administration of Cytisine (in standard and prolonged administration) + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: spirometry with CO test (Diagnostic Test)
Smoking cessation
Smoking cessation through the administration of Cytisine (in standard and prolonged administration) + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: anthropometic data collection (Other)
Smoking cessation
Smoking cessation through the administration of Cytisine (in standard and prolonged administration) + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: blood test (Other)
Antinflammatory
reduction of inflammatory status through the administration of Acetylsalicylic acid, diet modification and physical activity increase + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: Acetylsalicylic acid (Drug)
Antinflammatory
reduction of inflammatory status through the administration of Acetylsalicylic acid, diet modification and physical activity increase + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: Diet Modification and Physical Activity Increase (Other)
Antinflammatory
reduction of inflammatory status through the administration of Acetylsalicylic acid, diet modification and physical activity increase + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: early lung cancer detection (Diagnostic Test)
Antinflammatory
reduction of inflammatory status through the administration of Acetylsalicylic acid, diet modification and physical activity increase + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: spirometry with CO test (Diagnostic Test)
Antinflammatory
reduction of inflammatory status through the administration of Acetylsalicylic acid, diet modification and physical activity increase + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: anthropometic data collection (Other)
Antinflammatory
reduction of inflammatory status through the administration of Acetylsalicylic acid, diet modification and physical activity increase + standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: blood test (Other)
Control Group
standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: early lung cancer detection (Diagnostic Test)
Control Group
standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: spirometry with CO test (Diagnostic Test)
Control Group
standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: anthropometic data collection (Other)
Control Group
standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
干预措施: blood test (Other)
结局指标
主要结局
Change in chronic inflammatory status
时间窗: 1 year
Reduction in the percentage of subjects with CRP\>=2 mg/L
次要结局
- Change in lung cancer incidence(3 years)
- Change in metabolic profile(1 year)
- Change in body mass index (BMI)(1 year)
- Change in waist circumference(1 year)
- Change in smoking status(1 year)
- Change in dietary habits(1 year)
- Change in the physical activity(1 year)
- Change in lung cancer specific and overall mortality(3 years)
研究者
Ugo Pastorino
Head of Thoracic Surgery Division
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano