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Screening and Multiple Intervention on Lung Epidemics (SMILE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03654105
Recruitment Status : Active, not recruiting
First Posted : August 31, 2018
Last Update Posted : February 28, 2023
Sponsor:
Collaborator:
Istituto Di Ricerche Farmacologiche Mario Negri
Information provided by (Responsible Party):
Ugo Pastorino, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Tracking Information
First Submitted Date  ICMJE August 14, 2018
First Posted Date  ICMJE August 31, 2018
Last Update Posted Date February 28, 2023
Actual Study Start Date  ICMJE July 23, 2019
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 29, 2018)		 Change in chronic inflammatory status [ Time Frame: 1 year ]
Reduction in the percentage of subjects with CRP>=2 mg/L
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2018)
  • Change in smoking status [ Time Frame: 1 year ]
    Reduction in the percentage of smokers
  • Change in dietary habits [ Time Frame: 1 year ]
    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.
  • Change in the physical activity [ Time Frame: 1 year ]
    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
  • Change in body mass index (BMI) [ Time Frame: 1 year ]
    Weight and height will be combined to report BMI in kg/m^2. Reduction in BMI
  • Change in waist circumference [ Time Frame: 1 year ]
    Reduction in waist circumference expressed in centimeters
  • Change in metabolic profile [ Time Frame: 1 year ]
    Enhancement in blood glucose, total cholesterol, LDL, HDL and triglycerides
  • Change in lung cancer incidence [ Time Frame: 3 years ]
    Reduction in lung cancer incidence
  • Change in lung cancer specific and overall mortality [ Time Frame: 3 years ]
    Reduction in lung cancer specific and overall mortality
Original Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2018)
  • Change in smoking status [ Time Frame: 1 year ]
    Reduction in the percentage of smokers
  • Change in dietary habits [ Time Frame: 1 year ]
    Adherence to the Mediterranean Diet measured by a self-reported questionnaire
  • Change in the physical activity [ Time Frame: 1 year ]
    Increase in the physical activity measured by IPAQ questionnaire (short form)
  • Change in body mass index (BMI) [ Time Frame: 1 year ]
    Weight and height will be combined to report BMI in kg/m^2. Reduction in BMI
  • Change in waist circumference [ Time Frame: 1 year ]
    Reduction in waist circumference expressed in centimeters
  • Change in metabolic profile [ Time Frame: 1 year ]
    Enhancement in blood glucose, total cholesterol, LDL, HDL and triglycerides
  • Change in lung cancer incidence [ Time Frame: 3 years ]
    Reduction in lung cancer incidence
  • Change in lung cancer specific and overall mortality [ Time Frame: 3 years ]
    Reduction in lung cancer specific and overall mortality
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Screening and Multiple Intervention on Lung Epidemics
Official Title  ICMJE Multifactorial Intervention of Primary Prevention in High Risk Subjects: a Randomized Trial
Brief 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 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Inflammation
  • Smoking Cessation
  • Diet Modification
  • Physical Activity
  • Lung Cancer
Intervention  ICMJE
  • Drug: Cytisine

    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.

    Other Name: ev code SUB31171
  • Drug: Acetylsalicylic acid
    The treatment will consist of Acetylsalicylic acid at 100mg once a day
    Other Name: Cardioaspirin
  • Other: Diet Modification and Physical Activity Increase

    It 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.
  • Diagnostic Test: early lung cancer detection
    standard treatment for early lung cancer detection with ultra low dose CT
  • Diagnostic Test: spirometry with CO test
    spirometry with CO test
  • Other: anthropometic data collection
    anthropometic data collection
  • Other: blood test
    blood test to assess the metabolic and inflammatory profile
Study Arms  ICMJE
  • Experimental: 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
    Interventions:
    • 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
  • Experimental: 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
    Interventions:
    • Drug: Cytisine
    • Diagnostic Test: early lung cancer detection
    • Diagnostic Test: spirometry with CO test
    • Other: anthropometic data collection
    • Other: blood test
  • Experimental: 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
    Interventions:
    • 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
    standard treatment for early lung cancer detection (ultra low dose CT) + spirometry with CO test + anthropometic data collection + blood test
    Interventions:
    • Diagnostic Test: early lung cancer detection
    • Diagnostic Test: spirometry with CO test
    • Other: anthropometic data collection
    • Other: blood test
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 29, 2018)		 2000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2026
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 55 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03654105
Other Study ID Numbers  ICMJE 2016-003036-20
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Ugo Pastorino, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Istituto Di Ricerche Farmacologiche Mario Negri
Investigators  ICMJE
Principal Investigator: Ugo Pastorino, MD IRCCS IstitutoNazionale dei Tumori di Milano
PRS Account Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Verification Date February 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP