InflammationPhase 2SMILENCT03654105
Screening and Multiple Intervention on Lung Epidemics
A Phase 2 study testing Cytisine, Acetylsalicylic acid and Diet Modification and Physical Activity Increase in people with Inflammation and Smoking Cessation, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 55 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Inflammation, Smoking Cessation, Diet Modification
- What is being tested?
- Cytisine, Acetylsalicylic acid and Diet Modification and Physical Activity Increase
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,000 participants
- Where
- 1 siteItaly
- Study dates
- 23 Jul 2019to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Multifactorial Intervention of Primary Prevention in High Risk Subjects: a Randomized Trial
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).
Read the detailed description
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).
At baseline each volunteer will undergo:
- questionnaires on population evaluation (e.g. socio-demographic, smoking habits, physical activity, etc)
- blood sampling for the assessment of the inflammatory and metabolic profile
- evaluation of respiratory function and measurement of carbon monoxide (CO)
- thorax ultra low-dose computed tomography (LDCT) without contrast
- anthropometric evaluation (e.g. weight, height, BMI, etc)
To reduce levels of chronic inflammation will be used:
- treatment with low-dose acetylsalicylic acid (ASA)
- dietary / nutritional intervention in order to promote an optimal diet, based on characteristic of the Mediterranean Diet, for weight maintenance, visceral fat control and an adequate nutritional status
- physical activity intervention, through the reduction of sedentary behaviour and the implementation of a moderate intensity activity of about 30 min a day
In the Smoking cessation will be used Cytisine. It is a molecule known since the early 60s for the treatment of smoking. In recent clinical trials it revealed efficacy in smoking cessation. In 2014, the NHS (National Health Service) produced a document evaluating the cost-effectiveness of drug treatment of smoking, concluding that cytisine has the most favorable profile among the drugs taken into consideration
The imaging will be performed by volumetric acquisition with a computed tomography scanner equipped with advanced technology hardware and software, including: high performance X-ray tube with low potential, high sensitivity detectors combined with dedicated reconstruction algorithms for optimisation of the signal to noise ratio within an ultra low radiation dose. The protocol for ultra-low dose computed tomography will be specifically set for lung cancer screening with semiautomated image analysis and nodule quantification, according to the international standard for image quality (Quantitative Imaging Biomarker Alliance). In particular, the ultra-low dose computed tomography protocol will be developed for the lowest radiation exposure and tested by dedicated phantom for quantitative analysis of imaging metrics.
In the control group subjects will receive an information booklet containing advice on an optimal lifestyle with particular reference to smoking, diet and physical activity according to the best international guidelines.
- Being tested
- Cytisine, Acetylsalicylic acid, Diet Modification and Physical Activity Increase, early lung cancer detection, spirometry with CO test
- Keywords
- Inflammation, Primary Prevention, Multiple Prevention, Lung Cancer Screening, Smoking Cessation, Diet, Physical Activity, CRP
- Medical subject headings
- Inflammation, Smoking Cessation, Motor Activity, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytisineDrug
Also called ev code SUB31171
Cytisine administration will be randomized 1:1 in standard (40 days)and prolonged treatment (84 days).
Subjects will be educated on how to take the product and informed about possible adverse effects.
Acetylsalicylic acidDrug
Also called Cardioaspirin
The treatment will consist of Acetylsalicylic acid at 100mg once a day
Diet Modification and Physical Activity IncreaseOther
It will be proposed:
- an optimal diet with the aim of favoring control of weight, abdominal fat and adequate nutritional status without increasing the levels of IGF-I and inflammatory factors or glycemic peaks, with periodic verification of the results
- a regular and sustainable physical activity program with periodic verification of the results.
early lung cancer detectionDiagnostic test
standard treatment for early lung cancer detection with ultra low dose CT
spirometry with CO testDiagnostic test
spirometry with CO test
anthropometic data collectionOther
anthropometic data collection
blood testOther
blood test to assess the metabolic and inflammatory profile
| Study group | Role | What they receive |
|---|---|---|
| Smoking cessation and Antinflammatory | Experimental | 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 Receives: Drug: Cytisine; Drug: Acetylsalicylic acid; Other: Diet Modification and Physical Activity Increase; Diagnostic Test: early lung cancer detection; Diagnostic Test: spirometry with CO test; Other: anthropometic data collection; Other: blood test |
| Smoking cessation | Experimental | 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 Receives: Drug: Cytisine; Diagnostic Test: early lung cancer detection; Diagnostic Test: spirometry with CO test; Other: anthropometic data collection; Other: blood test |
| Antinflammatory | Experimental | 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 Receives: Drug: Acetylsalicylic acid; Other: Diet Modification and Physical Activity Increase; Diagnostic Test: early lung cancer detection; Diagnostic Test: spirometry with CO test; Other: anthropometic data collection; Other: blood test |
| Control Group | Other | standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test Receives: Diagnostic Test: early lung cancer detection; Diagnostic Test: spirometry with CO test; Other: anthropometic data collection; Other: blood test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in chronic inflammatory status
Reduction in the percentage of subjects with CRP>=2 mg/L
Measured: 1 year
Secondary outcomes (8)
Change in smoking status
Reduction in the percentage of smokers
Measured: 1 year
Change in dietary habits
Dietary intakes are collected by a self reported food frequencies questionnaire and data are expressed as the average daily/weekly consumption of foods and food groups.
Servings size is defined as "natural unit" (e.g. 1 glass of soft drinks, 1 teaspoon of sugar) or as an average serving (e.g. 80 g of pasta or rice, 30 g of dried fruits).
The frequency of serving size is reported as continuous measure. Data will be collected as continuous measures and will be analyzed by performing statistical models to investigate a potential relationship among changes in dietary habits and anthropometric parameters (BMI, waist circumference..), socio-demographic characteristics (gender, smoking status, physical activity), biochemical parameters (CRP blood levels), drugs assumption and the risk of chronic diseases, such as lung cancer.
Measured: 1 year
Change in the physical activity
Increase in the physical activity measured by the validate short form IPAQ questionnaire (International Physical Activity Questionnaire) The items in the short IPAQ form were structured to provide separate scores on walking, moderate-intensity and vigorous-intensity activity. Computation of the total score requires summation of the duration (in minutes) and frequency (days) of each activity.
METs are multiples of the resting metabolic rate and a MET-minute is computed by multiplying the MET score of an activity by the minutes performed:
- Walking MET-minutes/week = 3.3 * walking minutes * walking days
- Moderate MET-minutes/week = 4.0 * moderate-intensity activity minutes * moderate days
- Vigorous MET-minutes/week = 8.0 * vigorous-intensity activity minutes * vigorous-intensity days
- Total physical activity MET-minutes/week = sum of Walking + Moderate + Vigorous MET-minutes/week scores
Measured: 1 year
Change in body mass index (BMI)
Weight and height will be combined to report BMI in kg/m^2. Reduction in BMI
Measured: 1 year
Change in waist circumference
Reduction in waist circumference expressed in centimeters
Measured: 1 year
Change in metabolic profile
Enhancement in blood glucose, total cholesterol, LDL, HDL and triglycerides
Measured: 1 year
Change in lung cancer incidence
Reduction in lung cancer incidence
Measured: 3 years
Change in lung cancer specific and overall mortality
Reduction in lung cancer specific and overall mortality
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2018
- Study start23 Jul 2019
- Primary completion31 Dec 2024
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (37)Papers the sponsor has linked to this study.
- Other trials for InflammationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
- Sponsor type
- University, hospital or other
- Collaborators
- Istituto Di Ricerche Farmacologiche Mario Negri
- Responsible party
- Principal investigator, Ugo Pastorino, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
- Investigators
- Ugo Pastorino, MD, Principal investigator, IRCCS IstitutoNazionale dei Tumori di Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03654105
- Sponsor's protocol ID
- 2016-003036-20
- Other IDs
- 2016
- Acronym
- SMILE
- Status last verified
- Mar 2026
- First submitted
- 14 Aug 2018
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pastorino U, Boffi R, Marchiano A, Sestini S, Munarini E, Calareso G, Boeri M, Pelosi G, Sozzi G, Silva M, Sverzellati N, Galeone C, La Vecchia C, Ghirardi A, Corrao G. Stopping Smoking Reduces Mortality in Low-Dose Computed Tomography Screening Participants. J Thorac Oncol. 2016 May;11(5):693-699. doi: 10.1016/j.jtho.2016.02.011. Epub 2016 Feb 24.
PubMed 26921675Pastorino U, Morelli D, Marchiano A, Sestini S, Suatoni P, Taverna F, Boeri M, Sozzi G, Cantarutti A, Corrao G. Inflammatory status and lung function predict mortality in lung cancer screening participants. Eur J Cancer Prev. 2018 Jul;27(4):289-295. doi: 10.1097/CEJ.0000000000000342.
PubMed 28333763Pastorino U, Morelli D, Leuzzi G, Gisabella M, Suatoni P, Taverna F, Bertocchi E, Boeri M, Sozzi G, Cantarutti A, Corrao G. Baseline and postoperative C-reactive protein levels predict mortality in operable lung cancer. Eur J Cancer. 2017 Jul;79:90-97. doi: 10.1016/j.ejca.2017.03.020. Epub 2017 May 1.
PubMed 28472743La Vecchia C, Gallus S, Garattini S. Effects of physical inactivity on non-communicable diseases. Lancet. 2012 Nov 3;380(9853):1553; author reply 1553-4. doi: 10.1016/S0140-6736(12)61872-8. No abstract available.
PubMed 23122239Bonaccio M, Cerletti C, Iacoviello L, de Gaetano G. Mediterranean diet and low-grade subclinical inflammation: the Moli-sani study. Endocr Metab Immune Disord Drug Targets. 2015;15(1):18-24. doi: 10.2174/1871530314666141020112146.
PubMed 25329200Lee Y, Kang D, Lee SA. Effect of dietary patterns on serum C-reactive protein level. Nutr Metab Cardiovasc Dis. 2014 Sep;24(9):1004-11. doi: 10.1016/j.numecd.2014.05.001. Epub 2014 May 27.
PubMed 24998076Bosetti C, Gallus S, Peto R, Negri E, Talamini R, Tavani A, Franceschi S, La Vecchia C. Tobacco smoking, smoking cessation, and cumulative risk of upper aerodigestive tract cancers. Am J Epidemiol. 2008 Feb 15;167(4):468-73. doi: 10.1093/aje/kwm318. Epub 2007 Dec 4.
PubMed 18056925Gallus S, Muttarak R, Martinez-Sanchez JM, Zuccaro P, Colombo P, La Vecchia C. Smoking prevalence and smoking attributable mortality in Italy, 2010. Prev Med. 2011 Jun;52(6):434-8. doi: 10.1016/j.ypmed.2011.03.011. Epub 2011 Mar 21.
PubMed 21421001Linseisen J, Rohrmann S, Miller AB, Bueno-de-Mesquita HB, Buchner FL, Vineis P, Agudo A, Gram IT, Janson L, Krogh V, Overvad K, Rasmuson T, Schulz M, Pischon T, Kaaks R, Nieters A, Allen NE, Key TJ, Bingham S, Khaw KT, Amiano P, Barricarte A, Martinez C, Navarro C, Quiros R, Clavel-Chapelon F, Boutron-Ruault MC, Touvier M, Peeters PH, Berglund G, Hallmans G, Lund E, Palli D, Panico S, Tumino R, Tjonneland A, Olsen A, Trichopoulou A, Trichopoulos D, Autier P, Boffetta P, Slimani N, Riboli E. Fruit and vegetable consumption and lung cancer risk: updated information from the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer. 2007 Sep 1;121(5):1103-14. doi: 10.1002/ijc.22807.
PubMed 17487840Lugo A, Asciutto R, Pacifici R, Colombo P, La Vecchia C, Gallus S. Smoking in Italy 2013-2014, with a focus on the young. Tumori. 2015 Sep-Oct;101(5):529-34. doi: 10.5301/tj.5000311. Epub 2015 May 15.
PubMed 25983096Peto J. Cancer epidemiology in the last century and the next decade. Nature. 2001 May 17;411(6835):390-5. doi: 10.1038/35077256.
PubMed 11357148Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT; Lancet Physical Activity Series Working Group. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet. 2012 Jul 21;380(9838):219-29. doi: 10.1016/S0140-6736(12)61031-9.
PubMed 22818936Carter BD, Abnet CC, Feskanich D, Freedman ND, Hartge P, Lewis CE, Ockene JK, Prentice RL, Speizer FE, Thun MJ, Jacobs EJ. Smoking and mortality--beyond established causes. N Engl J Med. 2015 Feb 12;372(7):631-40. doi: 10.1056/NEJMsa1407211.
PubMed 25671255Muezzinler A, Mons U, Gellert C, Schottker B, Jansen E, Kee F, O'Doherty MG, Kuulasmaa K, Freedman ND, Abnet CC, Wolk A, Hakansson N, Orsini N, Wilsgaard T, Bueno-de-Mesquita B, van der Schouw YT, Peeters PHM, de Groot LCPGM, Peters A, Orfanos P, Linneberg A, Pisinger C, Tamosiunas A, Baceviciene M, Luksiene D, Bernotiene G, Jousilahti P, Petterson-Kymmer U, Jansson JH, Soderberg S, Eriksson S, Jankovic N, Sanchez MJ, Veronesi G, Sans S, Drygas W, Trichopoulou A, Boffetta P, Brenner H. Smoking and All-cause Mortality in Older Adults: Results From the CHANCES Consortium. Am J Prev Med. 2015 Nov;49(5):e53-e63. doi: 10.1016/j.amepre.2015.04.004. Epub 2015 Jul 15.
PubMed 26188685Thun MJ, Carter BD, Feskanich D, Freedman ND, Prentice R, Lopez AD, Hartge P, Gapstur SM. 50-year trends in smoking-related mortality in the United States. N Engl J Med. 2013 Jan 24;368(4):351-64. doi: 10.1056/NEJMsa1211127.
PubMed 23343064
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multifactorial Intervention of Primary Prevention in High Risk Subjects: a Randomized Trial
- ClinicalTrials.gov ID
- NCT03654105
- Acronym / sponsor ID
- SMILE / 2016-003036-20
- Keywords
- Inflammation, Primary Prevention, Multiple Prevention, Lung Cancer Screening, Smoking Cessation, Diet, Physical Activity, CRP
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Collaborators
- Istituto Di Ricerche Farmacologiche Mario Negri
- Study start
- 23 Jul 2019 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 31 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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).
At baseline each volunteer will undergo:
- questionnaires on population evaluation (e.g. socio-demographic, smoking habits, physical activity, etc)
- blood sampling for the assessment of the inflammatory and metabolic profile
- evaluation of respiratory function and measurement of carbon monoxide (CO)
- thorax ultra low-dose computed tomography (LDCT) without contrast
- anthropometric evaluation (e.g. weight, height, BMI, etc)
To reduce levels of chronic inflammation will be used:
- treatment with low-dose acetylsalicylic acid (ASA)
- dietary / nutritional intervention in order to promote an optimal diet, based on characteristic of the Mediterranean Diet, for weight maintenance, visceral fat control and an adequate nutritional status
- physical activity intervention, through the reduction of sedentary behaviour and the implementation of a moderate intensity activity of about 30 min a day
In the Smoking cessation will be used Cytisine. It is a molecule known since the early 60s for the treatment of smoking. In recent clinical trials it revealed efficacy in smoking cessation. In 2014, the NHS (National Health Service) produced a document evaluating the cost-effectiveness of drug treatment of smoking, concluding that cytisine has the most favorable profile among the drugs taken into consideration
The imaging will be performed by volumetric acquisition with a computed tomography scanner equipped with advanced technology hardware and software, including: high performance X-ray tube with low potential, high sensitivity detectors combined with dedicated reconstruction algorithms for optimisation of the signal to noise ratio within an ultra low radiation dose. The protocol for ultra-low dose computed tomography will be specifically set for lung cancer screening with semiautomated image analysis and nodule quantification, according to the international standard for image quality (Quantitative Imaging Biomarker Alliance). In particular, the ultra-low dose computed tomography protocol will be developed for the lowest radiation exposure and tested by dedicated phantom for quantitative analysis of imaging metrics.
In the control group subjects will receive an information booklet containing advice on an optimal lifestyle with particular reference to smoking, diet and physical activity according to the best international guidelines.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Smoking cessation and Antinflammatory | Experimental | Drug: Cytisine, Drug: Acetylsalicylic acid, Other: Diet Modification and Physical Activity Increase, Diagnostic Test: early lung cancer detection, Diagnostic Test: spirometry with CO test, Other: anthropometic data collection, Other: blood testSmoking 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 |
| Smoking cessation | Experimental | Drug: Cytisine, Diagnostic Test: early lung cancer detection, Diagnostic Test: spirometry with CO test, Other: anthropometic data collection, Other: blood testSmoking 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 |
| Antinflammatory | Experimental | Drug: Acetylsalicylic acid, Other: Diet Modification and Physical Activity Increase, Diagnostic Test: early lung cancer detection, Diagnostic Test: spirometry with CO test, Other: anthropometic data collection, Other: blood testreduction 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 |
| Control Group | Other | Diagnostic Test: early lung cancer detection, Diagnostic Test: spirometry with CO test, Other: anthropometic data collection, Other: blood teststandard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test |
Who may qualify
- Ages
- 55 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CytisineAlso: ev code SUB31171Cytisine administration will be randomized 1:1 in standard (40 days)and prolonged treatment (84 days). Subjects will be educated on how to take the product and informed about possible adverse effects. | Drug | Smoking cessation, Smoking cessation and Antinflammatory |
| Acetylsalicylic acidAlso: CardioaspirinThe treatment will consist of Acetylsalicylic acid at 100mg once a day | Drug | Antinflammatory, Smoking cessation and Antinflammatory |
| Diet Modification and Physical Activity IncreaseIt will be proposed: 1. an optimal diet with the aim of favoring control of weight, abdominal fat and adequate nutritional status without increasing the levels of IGF-I and inflammatory factors or glycemic peaks, with periodic verification of the results 2. a regular and sustainable physical activity program with periodic verification of the results. | Other | Antinflammatory, Smoking cessation and Antinflammatory |
| early lung cancer detectionstandard treatment for early lung cancer detection with ultra low dose CT | Diagnostic test | Antinflammatory, Control Group, Smoking cessation, Smoking cessation and Antinflammatory |
| spirometry with CO testspirometry with CO test | Diagnostic test | Antinflammatory, Control Group, Smoking cessation, Smoking cessation and Antinflammatory |
| anthropometic data collectionanthropometic data collection | Other | Antinflammatory, Control Group, Smoking cessation, Smoking cessation and Antinflammatory |
| blood testblood test to assess the metabolic and inflammatory profile | Other | Antinflammatory, Control Group, Smoking cessation, Smoking cessation and Antinflammatory |
Primary outcome
Change in chronic inflammatory status
Time frame: 1 year
Reduction in the percentage of subjects with CRP>=2 mg/L
8 secondary outcomes
Change in smoking status
Time frame: 1 year
Change in dietary habits
Time frame: 1 year
Change in the physical activity
Time frame: 1 year
Change in body mass index (BMI)
Time frame: 1 year
Change in waist circumference
Time frame: 1 year
Change in metabolic profile
Time frame: 1 year
Change in lung cancer incidence
Time frame: 3 years
Change in lung cancer specific and overall mortality
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Background: PubMed 26921675Pastorino U, Boffi R, Marchiano A, Sestini S, Munarini E, Calareso G, Boeri M, Pelosi G, Sozzi G, Silva M, Sverzellati N, Galeone C, La Vecchia C, Ghirardi A, Corrao G. Stopping Smoking Reduces Mortality in Low-Dose Computed Tomography Screening Participants. J Thorac Oncol. 2016 May;11(5):693-699. doi: 10.1016/j.jtho.2016.02.011. Epub 2016 Feb 24.
- Background: PubMed 28333763Pastorino U, Morelli D, Marchiano A, Sestini S, Suatoni P, Taverna F, Boeri M, Sozzi G, Cantarutti A, Corrao G. Inflammatory status and lung function predict mortality in lung cancer screening participants. Eur J Cancer Prev. 2018 Jul;27(4):289-295. doi: 10.1097/CEJ.0000000000000342.
- Background: PubMed 28472743Pastorino U, Morelli D, Leuzzi G, Gisabella M, Suatoni P, Taverna F, Bertocchi E, Boeri M, Sozzi G, Cantarutti A, Corrao G. Baseline and postoperative C-reactive protein levels predict mortality in operable lung cancer. Eur J Cancer. 2017 Jul;79:90-97. doi: 10.1016/j.ejca.2017.03.020. Epub 2017 May 1.
- Background: PubMed 23122239La Vecchia C, Gallus S, Garattini S. Effects of physical inactivity on non-communicable diseases. Lancet. 2012 Nov 3;380(9853):1553; author reply 1553-4. doi: 10.1016/S0140-6736(12)61872-8. No abstract available.
- Background: PubMed 25329200Bonaccio M, Cerletti C, Iacoviello L, de Gaetano G. Mediterranean diet and low-grade subclinical inflammation: the Moli-sani study. Endocr Metab Immune Disord Drug Targets. 2015;15(1):18-24. doi: 10.2174/1871530314666141020112146.
- Background: PubMed 24998076Lee Y, Kang D, Lee SA. Effect of dietary patterns on serum C-reactive protein level. Nutr Metab Cardiovasc Dis. 2014 Sep;24(9):1004-11. doi: 10.1016/j.numecd.2014.05.001. Epub 2014 May 27.
- Background: PubMed 18056925Bosetti C, Gallus S, Peto R, Negri E, Talamini R, Tavani A, Franceschi S, La Vecchia C. Tobacco smoking, smoking cessation, and cumulative risk of upper aerodigestive tract cancers. Am J Epidemiol. 2008 Feb 15;167(4):468-73. doi: 10.1093/aje/kwm318. Epub 2007 Dec 4.
- Background: PubMed 21421001Gallus S, Muttarak R, Martinez-Sanchez JM, Zuccaro P, Colombo P, La Vecchia C. Smoking prevalence and smoking attributable mortality in Italy, 2010. Prev Med. 2011 Jun;52(6):434-8. doi: 10.1016/j.ypmed.2011.03.011. Epub 2011 Mar 21.
- Background: PubMed 17487840Linseisen J, Rohrmann S, Miller AB, Bueno-de-Mesquita HB, Buchner FL, Vineis P, Agudo A, Gram IT, Janson L, Krogh V, Overvad K, Rasmuson T, Schulz M, Pischon T, Kaaks R, Nieters A, Allen NE, Key TJ, Bingham S, Khaw KT, Amiano P, Barricarte A, Martinez C, Navarro C, Quiros R, Clavel-Chapelon F, Boutron-Ruault MC, Touvier M, Peeters PH, Berglund G, Hallmans G, Lund E, Palli D, Panico S, Tumino R, Tjonneland A, Olsen A, Trichopoulou A, Trichopoulos D, Autier P, Boffetta P, Slimani N, Riboli E. Fruit and vegetable consumption and lung cancer risk: updated information from the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer. 2007 Sep 1;121(5):1103-14. doi: 10.1002/ijc.22807.
- Background: PubMed 25983096Lugo A, Asciutto R, Pacifici R, Colombo P, La Vecchia C, Gallus S. Smoking in Italy 2013-2014, with a focus on the young. Tumori. 2015 Sep-Oct;101(5):529-34. doi: 10.5301/tj.5000311. Epub 2015 May 15.
- Background: PubMed 11357148Peto J. Cancer epidemiology in the last century and the next decade. Nature. 2001 May 17;411(6835):390-5. doi: 10.1038/35077256.
- Background: PubMed 22818936Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT; Lancet Physical Activity Series Working Group. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet. 2012 Jul 21;380(9838):219-29. doi: 10.1016/S0140-6736(12)61031-9.
- WHO report on the global tobacco epidemic, 2015Link provided by the sponsor.
- Ministero della Salute, Istituto Superiore di Sanità. Linee guida cliniche per promuovere la cessazione dell'abitudine al fumo. Guida breve per la realizzazione degli interventi.Link provided by the sponsor.
- AIRC. Fumo: le domande più frequenti. Perché si insiste tanto sui rischi del fumo?Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ugo Pastorino, MD principal investigator
IRCCS IstitutoNazionale dei Tumori di Milano
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cytisine, Acetylsalicylic acid and Diet Modification and Physical Activity Increase in people with Inflammation and Smoking Cessation, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in chronic inflammatory status (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03654105, which also lists 37 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.