Lung Cancer
Conditions
Keywords
Sulforaphane, Chemoprevention, Former Smokers
Brief summary
This research study involves taking an experimental anti-cancer dietary supplement called Sulforaphane (SF) or a placebo (product without any supplement content) over a period of twelve months in order to determine if it is a useful dietary supplement for prevention of lung cancer in humans. The main goals of this research study are: 1. To learn about the effects of giving Sulforaphane (SF) to former smokers who are still at high risk of developing cancer due to their smoking history and whether or not their condition improves, stays the same or becomes worse after Sulforaphane (SF) is given. 2. To learn whether Sulforaphane (SF) might reverse some of the lung cell changes associated with future development of lung cancer.
Interventions
DIETARY_SUPPLEMENTSulforaphane
Sulforaphane (SF) is a naturally occurring substance (phytochemical) found in cruciferous vegetables.
DRUGPlacebo
Inactive ingredients
Sponsors
National Cancer Institute (NCI)
Jian-Min Yuan, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double Blind
Eligibility
Sex/Gender
ALL
Age
55 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Man or woman 55-75 years of age. 2. Patients with normal endobronchial biopsy findings or pre-cancerous lesions at baseline will be eligible for the study. Pre-cancerous lesions include (a) reserve cell hyperplasia, (b) squamous metaplasia, (c) mild dysplasia, (d) moderate dysplasia, and (e) severe dysplasia. 3. A former smoker who has a history of smoking with ≥30 pack-years, quits smoking within the past 10 years, and has ≥1 year sustained abstinence from smoking. 4. Female subjects must be of non-child bearing potential or must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication) if of childbearing potential. 5. Male and female subjects of childbearing potential must be willing to use adequate barrier methods of contraception from the time starting with the screening visit through 30 days after the last dose of study therapy. 6. Abstinence is acceptable if this is the established and preferred contraception for the subject. 7. Generally healthy with liver enzyme and blood count values within the ranges shown below on the blood sample drawn at the baseline screening visit. Specifically: White blood cells ≥ 3,000/mL Total bilirubin ≤ 1.5 x ULN (upper limits of normal) AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN BUN and serum creatinine ≤ 1.5 x ULN Serum pregnancy test Negative 8. The presence of airflow obstruction on spirometry (GOLD II or greater, Forced Expiratory Volume in the first second (FEV1) \<80%) Chronic Obstructive Pulmonary Disease (COPD); and/or any emphysema on CT scan. 9. Participants must have a Southwest Oncology Group (SWOG) performance status of 0-2 10. Participants must be able and willing to undergo a bronchoscopy before and after treatment for 12 months. 11. Patients must be fully informed of the investigational nature of this study and must sign an informed consent in accordance within institutional and regulatory guidelines.
Exclusion criteria
1. Carcinoma in situ or invasive cancer on baseline endobronchial biopsy. 2. A malignancy except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. 3. Severe lung disease or inability to undergo two bronchoscopies. 4. Had pneumonia or acute bronchitis for at least 2 weeks prior to enrollment. 5. Cardiac dysrhythmia that is potentially life-threatening, such as ventricular tachycardia, multifocal premature ventricular contractions or supraventricular tachycardias with a rapid ventricular response. Well-controlled atrial fibrillation or rare (\< 2 minutes) premature ventricular contractions are not exclusionary. 6. Evidence of clinically active coronary artery disease, including myocardial infarction within 6 weeks, chest pain, or congestive heart failure, or any serious medical condition which would preclude a patient from undergoing a bronchoscopy or would jeopardize the goals of the study. 7. Hypoxemia (less than 90% saturation with supplemental oxygen). 8. Prior chemotherapy or thoracic radiation within the past 5 years. 9. Woman who is pregnant or plan to be pregnant in next 12 months, or is breast feeding or plan to begin breast feeding in next 12 months. 10. Life expectancy of \< 12 months. 11. Have a history of irritable bowel disease such as Crohn's disease and ulcerative colitis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Bronchial Dysplasia Index at 12 Months | 12 months | To explore if daily oral dose of 120 micromole SF can modulate the changes in bronchial dysplasia from endoscopic biopsies in former smokers at high risk for lung cancer. All bronchial biopsies were formalin fixed, paraffin embedded, and H&E stained for subsequent morphologic evaluation and classification defined by the World Health Organization The scale to score the biopsy: 1= normal; 2= reserve cell hyperplasia; 3 = squamous metaplasia; 4 = mild dysplasia; 5 = moderate dysplasia; 6 = severe dysplasia; 7 = carcinoma in situ; and 8 = invasive carcinoma. The higher the score the worse the possible outcome. |
| Cell Proliferation Marker Ki-67 | 12 months | The primary outcome focuses on the changes of bronchial dysplasia index with cell proliferation marker Ki-67. The determination if a daily oral dose of 120 micromole SF for 12 months can modulate the changes of bronchial dysplasia index, cell proliferation marker Ki-67. Besides the inhibition of tumor incidence and multiplicity, the use of sulforaphane can inhibit cellular proliferation markers such as Ki-67 and induction of apoptosis hallmarks of tumorigenesis. Ki-67 will be quantified as % positive cells in two slides of each tissue block. First, we calculate the average values of each of the 3 IHC markers over 6 tissue blocks within each bronchoscopy per patient separately for pre- and post-treatment. The primary analysis for these continuous measures will be a linear regression predicting post-treatment score by treatment group, controlling for pre-treatment score. |
| Apoptosis Marker TUNEL | 12 months | The determination if a daily oral dose of 120 micromole SF for 12 months can modulate the changes of bronchial dysplasia index, in apoptosis marker TUNEL in bronchial biopsies in former smokers at high risk for lung cancer. TUNEL will be quantified as % positive cells in two slides of each tissue block. First, we calculate the average values of each of the 3 IHC markers over 6 tissue blocks within each bronchoscopy per patient separately for pre- and post-treatment. The primary analysis for these continuous measures will be a linear regression predicting post-treatment score by treatment group, controlling for pre-treatment score. |
| Apoptosis Marker Caspase-3 | 12 months | The determination if a daily oral dose of 120 micromole SF for 12 months can modulate the changes of bronchial dysplasia index, in apoptosis marker Caspase-3 in bronchial biopsies in former smokers at high risk for lung cancer. Caspase-3 will be quantified as % positive cells in two slides of each tissue block. First, we calculate the average values of each of the 3 IHC markers over 6 tissue blocks within each bronchoscopy per patient separately for pre- and post-treatment. The primary analysis for these continuous measures will be a linear regression predicting post-treatment score by treatment group, controlling for pre-treatment score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Upregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples | 12 months | Similarly, GSVA algorithm was used to calculate gene set enrichment scores in nasal brushing samples. If a gene is upregulated in lung cancer (LC), the inhibitory effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against LC. |
| Downregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples | 12 months | GSVA algorithm was used to calculate gene set enrichment scores in nasal brushing samples. If a gene is downregulated in lung cancer (LC), the enhancing effect of sulforaphane (SFN) treatment on such genes also suggests a protective effect against LC. |
| Upregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples | 12 Months | Gene set variation analysis (GSVA) algorithm was used to calculate gene set enrichment scores in bronchial brushing samples. If a gene is upregulated in lung cancer (LC) tissue, the inhibitory effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against LC. |
| Downregulated Genes Associated With Risk of Lung Pre-malignant Lesions (PML) in Nasal Brushing Samples | 12 months | Similarly, GSVA algorithm was used to calculate gene set enrichment scores in nasal brushing samples. If a gene is downregulated in PML, the overexpression effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against PML |
| Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | 12 Months | To determine the safety and toxicity of daily oral dose of 120 micromole SF in former smokers at high risk for lung cancer by monitoring and recording any potential SF-related adverse events (both expected and unexpected events). The severity is calculated by five grades: 1=mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death. Events are assigned to categories of unrelated, possibly elated, probably related, and related. |
| Upregulated Genes Associated With Risk of Lung Pre-malignant Lesions Cancer (PML) in Nasal Brushing Samples | 12 months | GSVA algorithm was used to calculate gene set enrichment scores in nasal brushing samples. If a gene is upregulated in PML. the inhibitory effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against PML risk. |
| Downregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples | 12 months | Gene set variation analysis (GSVA) algorithm was used to calculate gene set enrichment scores in bronchial brushing samples. If a gene is downregulated in LC, the enhancing effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against LC. |
| Upregulated Genes Associated With Lung Pre-Malignant Lesions (PML) in Bronchial Brushing Samples | 12 months | GSVA algorithm was used to calculate gene set enrichment scores in bronchial brushing samples. If a gene is upregulated in lung pre-malignant lesions (PML), the inhibitory effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against PML. |
| Downregulated Genes Associated With Lung Pre-malignant Lesions (PML) in Bronchial Brushing Samples | 12 months | GSVA algorithm was used to calculate gene set enrichment scores in bronchial brushing samples. If a gene is downregulated in PML, the enhancing effect of sulforaphane (SFN) treatment on such genes also suggests a protective effect against PML. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sulforaphane (Study Drug) Sulforaphane four tablets 2 times per day with breakfast and dinner each dose contains approximately 120 micromole of Sulforaphane
Sulforaphane: Sulforaphane (SF) is a naturally occurring substance (phytochemical) found in cruciferous vegetables. | 17 |
| Placebo Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner
Placebo: Inactive ingredients | 20 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Sulforaphane (Study Drug) | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 64.1 years STANDARD_DEVIATION 5.3 | 66.2 years STANDARD_DEVIATION 4.7 | 68.0 years STANDARD_DEVIATION 3.2 |
| Education levels College | 12 Participants | 23 Participants | 11 Participants |
| Education levels Graduate school | 2 Participants | 6 Participants | 4 Participants |
| Education levels High school or less | 3 Participants | 8 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 37 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 36 Participants | 19 Participants |
| Sex: Female, Male Female | 4 Participants | 15 Participants | 11 Participants |
| Sex: Female, Male Male | 13 Participants | 22 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 22 |
| other Total, other adverse events | 21 / 21 | 22 / 22 |
| serious Total, serious adverse events | 0 / 21 | 0 / 22 |
Outcome results
Primary
Apoptosis Marker Caspase-3
The determination if a daily oral dose of 120 micromole SF for 12 months can modulate the changes of bronchial dysplasia index, in apoptosis marker Caspase-3 in bronchial biopsies in former smokers at high risk for lung cancer. Caspase-3 will be quantified as % positive cells in two slides of each tissue block. First, we calculate the average values of each of the 3 IHC markers over 6 tissue blocks within each bronchoscopy per patient separately for pre- and post-treatment. The primary analysis for these continuous measures will be a linear regression predicting post-treatment score by treatment group, controlling for pre-treatment score.
Time frame: 12 months
Population: Caspase-3 positive cytoplasm (% of total cells examined)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Sulforaphane (Study Drug) | Apoptosis Marker Caspase-3 | Baseline: All positive cells | 4.46 percent of cells |
| Sulforaphane (Study Drug) | Apoptosis Marker Caspase-3 | Baseline: Weak-intensity positive cells | 4.18 percent of cells |
| Sulforaphane (Study Drug) | Apoptosis Marker Caspase-3 | Baseline: Moderate-intensity positive cells | 0.25 percent of cells |
| Sulforaphane (Study Drug) | Apoptosis Marker Caspase-3 | Baseline: Strong-intensity positive cells | 0.04 percent of cells |
| Sulforaphane (Study Drug) | Apoptosis Marker Caspase-3 | Pre to Post Treatment: All positive cells | -1.28 percent of cells |
| Sulforaphane (Study Drug) | Apoptosis Marker Caspase-3 | Pre to Post Treatment: Weak-intensity positive cells | -1.19 percent of cells |
| Sulforaphane (Study Drug) | Apoptosis Marker Caspase-3 | Pre to Post Treatment: Moderate-intensity positive cells | -0.07 percent of cells |
| Sulforaphane (Study Drug) | Apoptosis Marker Caspase-3 | Pre to Post Treatment: Strong-intensity positive cells | -0.01 percent of cells |
| Placebo | Apoptosis Marker Caspase-3 | Pre to Post Treatment: Strong-intensity positive cells | -0.03 percent of cells |
| Placebo | Apoptosis Marker Caspase-3 | Baseline: All positive cells | 2.96 percent of cells |
| Placebo | Apoptosis Marker Caspase-3 | Pre to Post Treatment: All positive cells | -1.00 percent of cells |
| Placebo | Apoptosis Marker Caspase-3 | Baseline: Weak-intensity positive cells | 2.69 percent of cells |
| Placebo | Apoptosis Marker Caspase-3 | Pre to Post Treatment: Moderate-intensity positive cells | -0.14 percent of cells |
| Placebo | Apoptosis Marker Caspase-3 | Baseline: Moderate-intensity positive cells | 0.25 percent of cells |
| Placebo | Apoptosis Marker Caspase-3 | Pre to Post Treatment: Weak-intensity positive cells | -0.83 percent of cells |
| Placebo | Apoptosis Marker Caspase-3 | Baseline: Strong-intensity positive cells | 0.02 percent of cells |
Comparison: All positive nuclei. Mean (95%CI) at baseline.p-value: 0.295Analysis of Covariance
Comparison: weak intensity positive nuclei. Mean (95%CI) at baseline.p-value: 0.242Analysis of Covariance
Comparison: Moderate intensity positive nuclei. Mean (95%CI) at baseline.p-value: 0.985Analysis of Covariance
Comparison: Strong intensity positive nuclei. Mean (95%CI) at baseline.p-value: 0.547Analysis of Covariance
Comparison: All positive nuclei. Mean (95%CI) changes from pre to pos treatment.p-value: 0.778Analysis of Covariance
Comparison: Weak intensity positive nuclei. Mean (95%CI) changes from pre to pos treatment.p-value: 0.685Analysis of Covariance
Comparison: Moderate intensity positive nuclei. Mean (95%CI) changes from pre to pos treatment.p-value: 0.469Analysis of Covariance
Comparison: strong intensity positive nuclei. Mean (95%CI) changes from pre to pos treatment.p-value: 0.052Analysis of Covariance
Primary
Apoptosis Marker TUNEL
The determination if a daily oral dose of 120 micromole SF for 12 months can modulate the changes of bronchial dysplasia index, in apoptosis marker TUNEL in bronchial biopsies in former smokers at high risk for lung cancer. TUNEL will be quantified as % positive cells in two slides of each tissue block. First, we calculate the average values of each of the 3 IHC markers over 6 tissue blocks within each bronchoscopy per patient separately for pre- and post-treatment. The primary analysis for these continuous measures will be a linear regression predicting post-treatment score by treatment group, controlling for pre-treatment score.
Time frame: 12 months
Population: TUNEL positive nuclei (counts/µm2) Mean (95% CI) changes from baseline and pre- to post-treatment
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Sulforaphane (Study Drug) | Apoptosis Marker TUNEL | Baseline: All positive nuclei | 5.01 counts/µm2 |
| Sulforaphane (Study Drug) | Apoptosis Marker TUNEL | Baseline: Weak-intensity positive nuclei | 2.73 counts/µm2 |
| Sulforaphane (Study Drug) | Apoptosis Marker TUNEL | Baseline: Moderate-intensity positive nuclei | 1.78 counts/µm2 |
| Sulforaphane (Study Drug) | Apoptosis Marker TUNEL | Baseline: Strong-intensity positive nuclei | 0.50 counts/µm2 |
| Sulforaphane (Study Drug) | Apoptosis Marker TUNEL | Pre to Post Treatment: All positive nuclei | -0.21 counts/µm2 |
| Sulforaphane (Study Drug) | Apoptosis Marker TUNEL | Pre to Post Treatment: Weak-intensity positive nuclei | -0.05 counts/µm2 |
| Sulforaphane (Study Drug) | Apoptosis Marker TUNEL | Pre to Post Treatment: Moderate-intensity positive nuclei | -0.10 counts/µm2 |
| Sulforaphane (Study Drug) | Apoptosis Marker TUNEL | Pre to Post Treatment: Strong-intensity positive nuclei | -0.05 counts/µm2 |
| Placebo | Apoptosis Marker TUNEL | Pre to Post Treatment: Strong-intensity positive nuclei | 0.05 counts/µm2 |
| Placebo | Apoptosis Marker TUNEL | Baseline: All positive nuclei | 4.57 counts/µm2 |
| Placebo | Apoptosis Marker TUNEL | Pre to Post Treatment: All positive nuclei | 0.35 counts/µm2 |
| Placebo | Apoptosis Marker TUNEL | Baseline: Weak-intensity positive nuclei | 2.51 counts/µm2 |
| Placebo | Apoptosis Marker TUNEL | Pre to Post Treatment: Moderate-intensity positive nuclei | 0.16 counts/µm2 |
| Placebo | Apoptosis Marker TUNEL | Baseline: Moderate-intensity positive nuclei | 1.61 counts/µm2 |
| Placebo | Apoptosis Marker TUNEL | Pre to Post Treatment: Weak-intensity positive nuclei | 0.12 counts/µm2 |
| Placebo | Apoptosis Marker TUNEL | Baseline: Strong-intensity positive nuclei | 0.45 counts/µm2 |
Comparison: All positive nuclei. Mean (95%CI) baseline.p-value: 0.377Analysis of Covariance
Comparison: Weak-intensity positive nuclei. Mean (95%CI) baseline.p-value: 0.413Analysis of Covariance
Comparison: Moderate Intensity positive nuclei. Mean (95%CI) at baseline.p-value: 0.338Analysis of Covariance
Comparison: Strong-intensity positive nuclei. Mean (95%CI) baseline.p-value: 0.547Analysis of Covariance
Comparison: All positive nuclei. Mean (95%CI) changes from pre to pos treatment.p-value: 0.291Analysis of Covariance
Comparison: Weak-intensity positive nuclei. Mean (95%CI) changes from pre to pos treatment.p-value: 0.552Analysis of Covariance
Comparison: Moderate-intensity positive nuclei. Mean (95%CI) changes from pre to pos treatment.p-value: 0.205Analysis of Covariance
Comparison: Strong-intensity positive nuclei. Mean (95%CI) changes from pre to pos treatment.p-value: 0.295Analysis of Covariance
Primary
Cell Proliferation Marker Ki-67
The primary outcome focuses on the changes of bronchial dysplasia index with cell proliferation marker Ki-67. The determination if a daily oral dose of 120 micromole SF for 12 months can modulate the changes of bronchial dysplasia index, cell proliferation marker Ki-67. Besides the inhibition of tumor incidence and multiplicity, the use of sulforaphane can inhibit cellular proliferation markers such as Ki-67 and induction of apoptosis hallmarks of tumorigenesis. Ki-67 will be quantified as % positive cells in two slides of each tissue block. First, we calculate the average values of each of the 3 IHC markers over 6 tissue blocks within each bronchoscopy per patient separately for pre- and post-treatment. The primary analysis for these continuous measures will be a linear regression predicting post-treatment score by treatment group, controlling for pre-treatment score.
Time frame: 12 months
Population: Mean changes from the baseline and pre to post treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Sulforaphane (Study Drug) | Cell Proliferation Marker Ki-67 | Baseline: All positive nuclei | 26.07 counts per µm^2 |
| Sulforaphane (Study Drug) | Cell Proliferation Marker Ki-67 | Baseline: Weak-Intensity positive nuclei | 11.71 counts per µm^2 |
| Sulforaphane (Study Drug) | Cell Proliferation Marker Ki-67 | Baseline: Moderate Intensity positive nuclei | 6.70 counts per µm^2 |
| Sulforaphane (Study Drug) | Cell Proliferation Marker Ki-67 | Baseline: Strong intensity positive nuclei | 7.67 counts per µm^2 |
| Sulforaphane (Study Drug) | Cell Proliferation Marker Ki-67 | Pre to Post Treatment: All positive nuclei | -5.27 counts per µm^2 |
| Sulforaphane (Study Drug) | Cell Proliferation Marker Ki-67 | Pre to Post Treatment: Weak-intensity positive nuclei | -0.50 counts per µm^2 |
| Sulforaphane (Study Drug) | Cell Proliferation Marker Ki-67 | Pre to Post Treatment: Moderate-intensity positive nuclei | -1.16 counts per µm^2 |
| Sulforaphane (Study Drug) | Cell Proliferation Marker Ki-67 | Pre to Post Treatment: Strong-intensity positive nuclei | -3.41 counts per µm^2 |
| Placebo | Cell Proliferation Marker Ki-67 | Pre to Post Treatment: Strong-intensity positive nuclei | 5.93 counts per µm^2 |
| Placebo | Cell Proliferation Marker Ki-67 | Baseline: All positive nuclei | 27.75 counts per µm^2 |
| Placebo | Cell Proliferation Marker Ki-67 | Pre to Post Treatment: All positive nuclei | 18.03 counts per µm^2 |
| Placebo | Cell Proliferation Marker Ki-67 | Baseline: Weak-Intensity positive nuclei | 12.21 counts per µm^2 |
| Placebo | Cell Proliferation Marker Ki-67 | Pre to Post Treatment: Moderate-intensity positive nuclei | 4.61 counts per µm^2 |
| Placebo | Cell Proliferation Marker Ki-67 | Baseline: Moderate Intensity positive nuclei | 7.22 counts per µm^2 |
| Placebo | Cell Proliferation Marker Ki-67 | Pre to Post Treatment: Weak-intensity positive nuclei | 7.48 counts per µm^2 |
| Placebo | Cell Proliferation Marker Ki-67 | Baseline: Strong intensity positive nuclei | 8.32 counts per µm^2 |
Comparison: All positive nuclei. Mean (95%CI) changes in baseline.p-value: 0.738Analysis of Covariance
Comparison: Weak-intensity positive nuclei. Mean (95%CI) baseline.p-value: 0.78Analysis of Covariance
Comparison: Moderate intensity positive nuclei. Mean (95%CI) changes in baseline.p-value: 0.733Analysis of Covariance
Comparison: Strong-Intensity positive nuclei. Mean (95%CI) changes in baseline.p-value: 0.751Analysis of Covariance
Comparison: All positive nuclei. Mean (95%CI) changes from pre to pos treatment.p-value: 0.014Analysis of Covariance
Comparison: Week intensity positive nuclei. Mean (95%CI) changes from pre to pos treatment.p-value: 0.056Covariance
Comparison: Moderate Intensity positive nuclei. Mean (95%CI) changes from pre to pos treatment.p-value: 0.028Analysis of Covariance
Comparison: Strong intensity positive nuclei. Mean (95%CI) changes from pre to pos treatment.p-value: 0.004Analysis of Covariance
Primary
Change From Baseline in Bronchial Dysplasia Index at 12 Months
To explore if daily oral dose of 120 micromole SF can modulate the changes in bronchial dysplasia from endoscopic biopsies in former smokers at high risk for lung cancer. All bronchial biopsies were formalin fixed, paraffin embedded, and H&E stained for subsequent morphologic evaluation and classification defined by the World Health Organization The scale to score the biopsy: 1= normal; 2= reserve cell hyperplasia; 3 = squamous metaplasia; 4 = mild dysplasia; 5 = moderate dysplasia; 6 = severe dysplasia; 7 = carcinoma in situ; and 8 = invasive carcinoma. The higher the score the worse the possible outcome.
Time frame: 12 months
Population: Mean change from pre to post treatment (95%) confidence interval.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane (Study Drug) | Change From Baseline in Bronchial Dysplasia Index at 12 Months | Pre treatment | 1.67 score | Standard Deviation 0.38 |
| Sulforaphane (Study Drug) | Change From Baseline in Bronchial Dysplasia Index at 12 Months | Post treatment | 1.55 score | Standard Deviation 0.44 |
| Placebo | Change From Baseline in Bronchial Dysplasia Index at 12 Months | Pre treatment | 1.62 score | Standard Deviation 0.41 |
| Placebo | Change From Baseline in Bronchial Dysplasia Index at 12 Months | Post treatment | 1.48 score | Standard Deviation 0.37 |
Comparison: Derived from ANCOVA model with adjustment for baseline average endobronchial histopathological scores, age, sex, cigarettes per day, years of smoking, and years since quit smoking.p-value: 0.45295% CI: [0.03, 0.41]ANCOVA
Comparison: Derived from ANCOVA model with adjustment for baseline average endobronchial histopathological scores, age, sex, cigarettes per day, years of smoking, and years since quit smoking.p-value: 0.45295% CI: [-0.04, 0.28]ANCOVA
Secondary
Downregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples
Gene set variation analysis (GSVA) algorithm was used to calculate gene set enrichment scores in bronchial brushing samples. If a gene is downregulated in LC, the enhancing effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against LC.
Time frame: 12 months
Population: Due to poor quality of RNA and missing data on the gene expression, we excluded 5 subjects in the sulforaphane group and 4 subjects in the placebo group. The final analysis for this secondary outcome included 12 subjects in the sulforaphane and 16 subjects in the placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane (Study Drug) | Downregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples | gene enrichment score pre-treatment | -0.10 Relative score from -1 to +1 | Standard Deviation 0.27 |
| Sulforaphane (Study Drug) | Downregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples | gene enrichment score post-treatment | -0.03 Relative score from -1 to +1 | Standard Deviation 0.35 |
| Placebo | Downregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples | gene enrichment score pre-treatment | -0.07 Relative score from -1 to +1 | Standard Deviation 0.25 |
| Placebo | Downregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples | gene enrichment score post-treatment | 0.08 Relative score from -1 to +1 | Standard Deviation 0.28 |
p-value: 0.5Mixed Models Analysis
Secondary
Downregulated Genes Associated With Lung Pre-malignant Lesions (PML) in Bronchial Brushing Samples
GSVA algorithm was used to calculate gene set enrichment scores in bronchial brushing samples. If a gene is downregulated in PML, the enhancing effect of sulforaphane (SFN) treatment on such genes also suggests a protective effect against PML.
Time frame: 12 months
Population: Due to poor quality of RNA and missing data on the gene expression, we excluded 5 subjects in the sulforaphane group and 4 subjects in the placebo group. The final analysis for this secondary outcome included 12 subjects in the sulforaphane and 16 subjects in the placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane (Study Drug) | Downregulated Genes Associated With Lung Pre-malignant Lesions (PML) in Bronchial Brushing Samples | Downregulated gene enrichment score at pre-treatment | 0.20 relative score from -1 to +1 | Standard Deviation 0.37 |
| Sulforaphane (Study Drug) | Downregulated Genes Associated With Lung Pre-malignant Lesions (PML) in Bronchial Brushing Samples | Downregulated gene enrichment score at post-treatment | -0.15 relative score from -1 to +1 | Standard Deviation 0.4 |
| Placebo | Downregulated Genes Associated With Lung Pre-malignant Lesions (PML) in Bronchial Brushing Samples | Downregulated gene enrichment score at pre-treatment | 0.11 relative score from -1 to +1 | Standard Deviation 0.41 |
| Placebo | Downregulated Genes Associated With Lung Pre-malignant Lesions (PML) in Bronchial Brushing Samples | Downregulated gene enrichment score at post-treatment | -0.12 relative score from -1 to +1 | Standard Deviation 0.4 |
p-value: 0.5Mixed Models Analysis
Secondary
Downregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples
GSVA algorithm was used to calculate gene set enrichment scores in nasal brushing samples. If a gene is downregulated in lung cancer (LC), the enhancing effect of sulforaphane (SFN) treatment on such genes also suggests a protective effect against LC.
Time frame: 12 months
Population: Due to poor quality of RNA and missing data on the gene expression, we excluded 5 subjects in the sulforaphane group and 4 subjects in the placebo group. The final analysis for this secondary outcome included 12 subjects in the sulforaphane and 16 subjects in the placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane (Study Drug) | Downregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples | Gene enrichment score at pre-treatment | -0.29 relative score from -1 to +1 | Standard Deviation 0.33 |
| Sulforaphane (Study Drug) | Downregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples | Gene enrichment score at pre-treatment at post-treatment | 0.19 relative score from -1 to +1 | Standard Deviation 0.32 |
| Placebo | Downregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples | Gene enrichment score at pre-treatment | 0.02 relative score from -1 to +1 | Standard Deviation 0.37 |
| Placebo | Downregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples | Gene enrichment score at pre-treatment at post-treatment | 0.06 relative score from -1 to +1 | Standard Deviation 0.34 |
p-value: 0.0045Mixed Models Analysis
Secondary
Downregulated Genes Associated With Risk of Lung Pre-malignant Lesions (PML) in Nasal Brushing Samples
Similarly, GSVA algorithm was used to calculate gene set enrichment scores in nasal brushing samples. If a gene is downregulated in PML, the overexpression effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against PML
Time frame: 12 months
Population: Due to poor quality of RNA and missing data on the gene expression, we excluded 5 subjects in the sulforaphane group and 4 subjects in the placebo group. The final analysis for this secondary outcome included 12 subjects in the sulforaphane and 16 subjects in the placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane (Study Drug) | Downregulated Genes Associated With Risk of Lung Pre-malignant Lesions (PML) in Nasal Brushing Samples | Gene enrichment score at pre-treatment | 0.28 relative score from -1 to +1 | Standard Deviation 0.38 |
| Sulforaphane (Study Drug) | Downregulated Genes Associated With Risk of Lung Pre-malignant Lesions (PML) in Nasal Brushing Samples | Gene enrichment score at pre-treatment at post-treatment | -0.01 relative score from -1 to +1 | Standard Deviation 0.41 |
| Placebo | Downregulated Genes Associated With Risk of Lung Pre-malignant Lesions (PML) in Nasal Brushing Samples | Gene enrichment score at pre-treatment | -0.12 relative score from -1 to +1 | Standard Deviation 0.42 |
| Placebo | Downregulated Genes Associated With Risk of Lung Pre-malignant Lesions (PML) in Nasal Brushing Samples | Gene enrichment score at pre-treatment at post-treatment | -0.07 relative score from -1 to +1 | Standard Deviation 0.42 |
p-value: 0.27Mixed Models Analysis
Secondary
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0
To determine the safety and toxicity of daily oral dose of 120 micromole SF in former smokers at high risk for lung cancer by monitoring and recording any potential SF-related adverse events (both expected and unexpected events). The severity is calculated by five grades: 1=mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death. Events are assigned to categories of unrelated, possibly elated, probably related, and related.
Time frame: 12 Months
Population: Total number of adverse events by attrition and severity by treatment group during the study period, The Pittsburgh Clinical Trial of Sulforaphane (SFN) on Risk Markers of Lung Cancer. The number of patients included those who dropped out from the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Possibly Related Grade 2 | 3 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Probably Related Grade 4 | 0 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Unrelated Grade 4 | 0 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Probably Related Grade 5 | 0 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Possibly Related Grade 3 | 0 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Related Grade 1 | 0 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Unrelated Grade 1 | 56 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Related Grade 2 | 0 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Possibly Related Grade 4 | 0 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Related Grade 3 | 0 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Unrelated Grade 5 | 0 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Related Grade 4 | 0 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Possibly Related Grade 5 | 0 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Related Grade 5 | 0 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Unrelated Grade 3 | 1 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | All adverse events Grade 1 | 85 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Probably Related Grade 1 | 3 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | All adverse events Grade 2 | 21 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Possibly Related Grade 1 | 26 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | All adverse events Grade 3 | 1 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Probably Related Grade 2 | 1 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | All adverse events Grade 4 | 0 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Unrelated Grade 2 | 17 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | All adverse events Grade 5 | 0 events |
| Sulforaphane (Study Drug) | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Probably Related Grade 3 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | All adverse events Grade 5 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Unrelated Grade 2 | 12 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Unrelated Grade 3 | 3 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Unrelated Grade 4 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Unrelated Grade 5 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Possibly Related Grade 1 | 12 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Possibly Related Grade 2 | 5 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Possibly Related Grade 3 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Possibly Related Grade 4 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Possibly Related Grade 5 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Probably Related Grade 1 | 1 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Probably Related Grade 2 | 1 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Probably Related Grade 3 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Probably Related Grade 4 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Probably Related Grade 5 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Related Grade 1 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Related Grade 2 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Related Grade 3 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Related Grade 4 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Related Grade 5 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | All adverse events Grade 1 | 79 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | All adverse events Grade 2 | 18 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | All adverse events Grade 3 | 3 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | All adverse events Grade 4 | 0 events |
| Placebo | Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 | Unrelated Grade 1 | 66 events |
p-value: 0.59Fisher Exact
p-value: 0.131Fisher Exact
Secondary
Upregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples
Gene set variation analysis (GSVA) algorithm was used to calculate gene set enrichment scores in bronchial brushing samples. If a gene is upregulated in lung cancer (LC) tissue, the inhibitory effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against LC.
Time frame: 12 Months
Population: Due to poor quality of RNA and missing data on the gene expression, we excluded 5 subjects in the sulforaphane group and 4 subjects in the placebo group. The final analysis for this secondary outcome included 12 subjects in the sulforaphane and 16 subjects in the placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane (Study Drug) | Upregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples | Gene enrichment score pre-treatment | 0.04 Relative score from -1 to +1 | Standard Deviation 0.25 |
| Sulforaphane (Study Drug) | Upregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples | Gene enrichment score post-treatment | 0.03 Relative score from -1 to +1 | Standard Deviation 0.32 |
| Placebo | Upregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples | Gene enrichment score pre-treatment | 0.02 Relative score from -1 to +1 | Standard Deviation 0.26 |
| Placebo | Upregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples | Gene enrichment score post-treatment | -0.02 Relative score from -1 to +1 | Standard Deviation 0.31 |
p-value: 0.82Mixed Models Analysis
Secondary
Upregulated Genes Associated With Lung Pre-Malignant Lesions (PML) in Bronchial Brushing Samples
GSVA algorithm was used to calculate gene set enrichment scores in bronchial brushing samples. If a gene is upregulated in lung pre-malignant lesions (PML), the inhibitory effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against PML.
Time frame: 12 months
Population: Due to poor quality of RNA and missing data on the gene expression, we excluded 5 subjects in the sulforaphane group and 4 subjects in the placebo group. The final analysis for this secondary outcome included 12 subjects in the sulforaphane and 16 subjects in the placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane (Study Drug) | Upregulated Genes Associated With Lung Pre-Malignant Lesions (PML) in Bronchial Brushing Samples | Upregulated gene enrichment score at pre-treatment | -0.27 relative score from -1 to +1 | Standard Deviation 0.41 |
| Sulforaphane (Study Drug) | Upregulated Genes Associated With Lung Pre-Malignant Lesions (PML) in Bronchial Brushing Samples | Upregulated gene enrichment score at post-treatment | 0.15 relative score from -1 to +1 | Standard Deviation 0.42 |
| Placebo | Upregulated Genes Associated With Lung Pre-Malignant Lesions (PML) in Bronchial Brushing Samples | Upregulated gene enrichment score at pre-treatment | -0.12 relative score from -1 to +1 | Standard Deviation 0.46 |
| Placebo | Upregulated Genes Associated With Lung Pre-Malignant Lesions (PML) in Bronchial Brushing Samples | Upregulated gene enrichment score at post-treatment | 0.11 relative score from -1 to +1 | Standard Deviation 0.41 |
p-value: 0.32Mixed Models Analysis
Secondary
Upregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples
Similarly, GSVA algorithm was used to calculate gene set enrichment scores in nasal brushing samples. If a gene is upregulated in lung cancer (LC), the inhibitory effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against LC.
Time frame: 12 months
Population: Due to poor quality of RNA and missing data on the gene expression, we excluded 5 subjects in the sulforaphane group and 4 subjects in the placebo group. The final analysis for this secondary outcome included 12 subjects in the sulforaphane and 16 subjects in the placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane (Study Drug) | Upregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples | Gene enrichment score at pre-treatment | 0.22 relative score from -1 to +1 | Standard Deviation 0.23 |
| Sulforaphane (Study Drug) | Upregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples | Gene enrichment score at pre-treatment at post-treatment | -0.15 relative score from -1 to +1 | Standard Deviation 0.17 |
| Placebo | Upregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples | Gene enrichment score at pre-treatment | 0.00 relative score from -1 to +1 | Standard Deviation 0.29 |
| Placebo | Upregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples | Gene enrichment score at pre-treatment at post-treatment | -0.07 relative score from -1 to +1 | Standard Deviation 0.25 |
p-value: 0.012Mixed Models Analysis
Secondary
Upregulated Genes Associated With Risk of Lung Pre-malignant Lesions Cancer (PML) in Nasal Brushing Samples
GSVA algorithm was used to calculate gene set enrichment scores in nasal brushing samples. If a gene is upregulated in PML. the inhibitory effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against PML risk.
Time frame: 12 months
Population: Due to poor quality of RNA and missing data on the gene expression, we excluded 5 subjects in the sulforaphane group and 4 subjects in the placebo group. The final analysis for this secondary outcome included 12 subjects in the sulforaphane and 16 subjects in the placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane (Study Drug) | Upregulated Genes Associated With Risk of Lung Pre-malignant Lesions Cancer (PML) in Nasal Brushing Samples | Gene enrichment score at pre-treatment | -0.27 relative score from -1 to +1 | Standard Deviation 0.42 |
| Sulforaphane (Study Drug) | Upregulated Genes Associated With Risk of Lung Pre-malignant Lesions Cancer (PML) in Nasal Brushing Samples | Gene enrichment score at pre-treatment at post-treatment | 0.08 relative score from -1 to +1 | Standard Deviation 0.46 |
| Placebo | Upregulated Genes Associated With Risk of Lung Pre-malignant Lesions Cancer (PML) in Nasal Brushing Samples | Gene enrichment score at pre-treatment | 0.08 relative score from -1 to +1 | Standard Deviation 0.47 |
| Placebo | Upregulated Genes Associated With Risk of Lung Pre-malignant Lesions Cancer (PML) in Nasal Brushing Samples | Gene enrichment score at pre-treatment at post-treatment | 0.09 relative score from -1 to +1 | Standard Deviation 0.46 |
p-value: 0.32Mixed Models Analysis