Trial Outcomes & Findings for Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers (NCT NCT03232138)

Last Updated: 2024-12-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

43 participants

Primary outcome timeframe

12 months

Results posted on

2024-12-17

Participant Flow

Participant milestones

Participant milestones
Measure	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.	Placebo Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
Overall Study STARTED	21	22
Overall Study COMPLETED	17	20
Overall Study NOT COMPLETED	4	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	Placebo Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
Overall Study Physician Decision	1	0
Overall Study Adverse Event	2	0
Overall Study Withdrawal by Subject	1	2

Baseline Characteristics

Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sulforaphane (Study Drug) n=17 Participants 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.	Placebo n=20 Participants Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients	Total n=37 Participants Total of all reporting groups
Age, Continuous	64.1 years STANDARD_DEVIATION 5.3 • n=5 Participants	68.0 years STANDARD_DEVIATION 3.2 • n=7 Participants	66.2 years STANDARD_DEVIATION 4.7 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	11 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	9 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants	20 Participants n=7 Participants	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants	19 Participants n=7 Participants	36 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Education levels High school or less	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Education levels College	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Education levels Graduate school	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Mean change from pre to post treatment (95%) confidence interval.

Outcome measures

Outcome measures
Measure	Sulforaphane (Study Drug) n=17 Participants 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.	Placebo n=20 Participants Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
Change From Baseline in Bronchial Dysplasia Index at 12 Months Pre treatment	1.67 score Standard Deviation 0.38	1.62 score Standard Deviation 0.41
Change From Baseline in Bronchial Dysplasia Index at 12 Months Post treatment	1.55 score Standard Deviation 0.44	1.48 score Standard Deviation 0.37

PRIMARY outcome

Timeframe: 12 months

Population: Mean changes from the baseline and pre to post treatment.

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.

Outcome measures

Outcome measures
Measure	Sulforaphane (Study Drug) n=17 Participants 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.	Placebo n=20 Participants Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
Cell Proliferation Marker Ki-67 Baseline: All positive nuclei	26.07 counts per µm^2 Interval 18.64 to 33.51	27.75 counts per µm^2 Interval 24.9 to 34.61
Cell Proliferation Marker Ki-67 Baseline: Weak-Intensity positive nuclei	11.71 counts per µm^2 Interval 8.85 to 14.57	12.21 counts per µm^2 Interval 9.57 to 14.85
Cell Proliferation Marker Ki-67 Baseline: Moderate Intensity positive nuclei	6.70 counts per µm^2 Interval 4.42 to 8.97	7.22 counts per µm^2 Interval 5.12 to 9.32
Cell Proliferation Marker Ki-67 Baseline: Strong intensity positive nuclei	7.67 counts per µm^2 Interval 4.61 to 10.72	8.32 counts per µm^2 Interval 5.51 to 11.14
Cell Proliferation Marker Ki-67 Pre to Post Treatment: All positive nuclei	-5.27 counts per µm^2 Interval -18.13 to 7.59	18.03 counts per µm^2 Interval 7.18 to 28.88
Cell Proliferation Marker Ki-67 Pre to Post Treatment: Weak-intensity positive nuclei	-0.50 counts per µm^2 Interval -6.44 to 5.26	7.48 counts per µm^2 Interval 2.55 to 12.41
Cell Proliferation Marker Ki-67 Pre to Post Treatment: Moderate-intensity positive nuclei	-1.16 counts per µm^2 Interval -4.76 to 2.44	4.61 counts per µm^2 Interval 1.57 to 7.64
Cell Proliferation Marker Ki-67 Pre to Post Treatment: Strong-intensity positive nuclei	-3.41 counts per µm^2 Interval -7.67 to 0.85	5.93 counts per µm^2 Interval 2.24 to 9.52

PRIMARY outcome

Timeframe: 12 months

Population: TUNEL positive nuclei (counts/µm2) Mean (95% CI) changes from baseline and pre- to post-treatment

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.

Outcome measures

Outcome measures
Measure	Sulforaphane (Study Drug) n=17 Participants 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.	Placebo n=20 Participants Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
Apoptosis Marker TUNEL Baseline: Weak-intensity positive nuclei	2.73 counts/µm2 Interval 2.33 to 3.13	2.51 counts/µm2 Interval 2.15 to 2.88
Apoptosis Marker TUNEL Baseline: Moderate-intensity positive nuclei	1.78 counts/µm2 Interval 1.52 to 2.04	1.61 counts/µm2 Interval 1.37 to 1.85
Apoptosis Marker TUNEL Baseline: Strong-intensity positive nuclei	0.50 counts/µm2 Interval 0.37 to 0.63	0.45 counts/µm2 Interval 0.33 to 0.57
Apoptosis Marker TUNEL Pre to Post Treatment: All positive nuclei	-0.21 counts/µm2 Interval -0.96 to 0.53	0.35 counts/µm2 Interval -0.27 to 0.96
Apoptosis Marker TUNEL Baseline: All positive nuclei	5.01 counts/µm2 Interval 4.28 to 5.75	4.57 counts/µm2 Interval 3.89 to 5.25
Apoptosis Marker TUNEL Pre to Post Treatment: Weak-intensity positive nuclei	-0.05 counts/µm2 Interval -0.43 to 0.34	0.12 counts/µm2 Interval -0.27 to 0.44
Apoptosis Marker TUNEL Pre to Post Treatment: Moderate-intensity positive nuclei	-0.10 counts/µm2 Interval -0.38 to 0.18	0.16 counts/µm2 Interval -0.08 to 0.39
Apoptosis Marker TUNEL Pre to Post Treatment: Strong-intensity positive nuclei	-0.05 counts/µm2 Interval -0.18 to 0.09	0.05 counts/µm2 Interval -0.06 to 0.17

PRIMARY outcome

Timeframe: 12 months

Population: Caspase-3 positive cytoplasm (% of total cells examined)

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.

Outcome measures

Outcome measures
Measure	Sulforaphane (Study Drug) n=17 Participants 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.	Placebo n=20 Participants Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
Apoptosis Marker Caspase-3 Baseline: All positive cells	4.46 percent of cells Interval 2.36 to 6.57	2.96 percent of cells Interval 1.02 to 4.9
Apoptosis Marker Caspase-3 Baseline: Weak-intensity positive cells	4.18 percent of cells Interval 2.31 to 6.04	2.69 percent of cells Interval 0.97 to 4.41
Apoptosis Marker Caspase-3 Baseline: Moderate-intensity positive cells	0.25 percent of cells Interval -0.01 to 0.5	0.25 percent of cells Interval 0.01 to 0.49
Apoptosis Marker Caspase-3 Baseline: Strong-intensity positive cells	0.04 percent of cells Interval -0.002 to 0.08	0.02 percent of cells Interval -0.02 to 0.06
Apoptosis Marker Caspase-3 Pre to Post Treatment: All positive cells	-1.28 percent of cells Interval -2.64 to 0.08	-1.00 percent of cells Interval -2.15 to 0.96
Apoptosis Marker Caspase-3 Pre to Post Treatment: Weak-intensity positive cells	-1.19 percent of cells Interval -2.44 to 0.06	-0.83 percent of cells Interval -1.88 to 0.23
Apoptosis Marker Caspase-3 Pre to Post Treatment: Moderate-intensity positive cells	-0.07 percent of cells Interval -0.21 to 0.08	-0.14 percent of cells Interval -0.26 to -0.02
Apoptosis Marker Caspase-3 Pre to Post Treatment: Strong-intensity positive cells	-0.01 percent of cells Interval -0.02 to -0.001	-0.03 percent of cells Interval -0.04 to -0.02

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Sulforaphane (Study Drug) n=44 Upregulated genes with lung cancer risk 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.	Placebo n=44 Upregulated genes with lung cancer risk Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
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	0.02 Relative score from -1 to +1 Standard Deviation 0.26
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	-0.02 Relative score from -1 to +1 Standard Deviation 0.31

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sulforaphane (Study Drug) n=113 upregulated gene with lung cancer risk 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.	Placebo n=113 upregulated gene with lung cancer risk Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
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	-0.07 Relative score from -1 to +1 Standard Deviation 0.25
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	0.08 Relative score from -1 to +1 Standard Deviation 0.28

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sulforaphane (Study Drug) n=61 Upregulated genes with PML risk 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.	Placebo n=61 Upregulated genes with PML risk Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
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	-0.12 relative score from -1 to +1 Standard Deviation 0.46
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	0.11 relative score from -1 to +1 Standard Deviation 0.41

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sulforaphane (Study Drug) n=153 upregulated gene with PML cancer risk 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.	Placebo n=153 upregulated gene with PML cancer risk Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
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	0.11 relative score from -1 to +1 Standard Deviation 0.41
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 0.40	-0.12 relative score from -1 to +1 Standard Deviation 0.40

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sulforaphane (Study Drug) n=41 Nasal upregulated genes with LC risk 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.	Placebo n=41 Nasal upregulated genes with LC risk Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
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	0.00 relative score from -1 to +1 Standard Deviation 0.29
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	-0.07 relative score from -1 to +1 Standard Deviation 0.25

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sulforaphane (Study Drug) n=116 Nasal upregulated genes with LC risk 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.	Placebo n=116 Nasal upregulated genes with LC risk Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
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	0.02 relative score from -1 to +1 Standard Deviation 0.37
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	0.06 relative score from -1 to +1 Standard Deviation 0.34

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sulforaphane (Study Drug) n=60 Nasal upregulated genes with LC risk 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.	Placebo n=60 Nasal upregulated genes with LC risk Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
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	0.08 relative score from -1 to +1 Standard Deviation 0.47
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	0.09 relative score from -1 to +1 Standard Deviation 0.46

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Sulforaphane (Study Drug) n=155 Nasal upregulated genes with LC risk 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.	Placebo n=155 Nasal upregulated genes with LC risk Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
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	-0.12 relative score from -1 to +1 Standard Deviation 0.42
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	-0.07 relative score from -1 to +1 Standard Deviation 0.42

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Sulforaphane (Study Drug) n=21 Participants 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.	Placebo n=22 Participants Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Unrelated Grade 5	0 events	0 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Possibly Related Grade 1	26 events	12 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Possibly Related Grade 5	0 events	0 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Probably Related Grade 1	3 events	1 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Probably Related Grade 3	0 events	0 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 All adverse events Grade 2	21 events	18 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 All adverse events Grade 5	0 events	0 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Unrelated Grade 1	56 events	66 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Unrelated Grade 2	17 events	12 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Unrelated Grade 3	1 events	3 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Unrelated Grade 4	0 events	0 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Possibly Related Grade 2	3 events	5 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Possibly Related Grade 3	0 events	0 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Possibly Related Grade 4	0 events	0 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Probably Related Grade 2	1 events	1 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Probably Related Grade 4	0 events	0 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Probably Related Grade 5	0 events	0 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Related Grade 1	0 events	0 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Related Grade 2	0 events	0 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Related Grade 3	0 events	0 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Related Grade 4	0 events	0 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 Related Grade 5	0 events	0 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 All adverse events Grade 1	85 events	79 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 All adverse events Grade 3	1 events	3 events
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0 All adverse events Grade 4	0 events	0 events

Adverse Events

Sulforaphane (Study Drug)

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Jian-Min Yuan M.D., Ph.D.

University of Pittsburgh Cancer Institute

Phone: 412-864-7889

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Sulforaphane (Study Drug) n=21 participants at risk 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.	Placebo n=22 participants at risk Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner Placebo: Inactive ingredients
Gastrointestinal disorders Bad taste	4.8% 1/21 • 1 year treatment, 1year post treatment	13.6% 3/22 • 1 year treatment, 1year post treatment
Gastrointestinal disorders Belching	19.0% 4/21 • 1 year treatment, 1year post treatment	27.3% 6/22 • 1 year treatment, 1year post treatment
Gastrointestinal disorders Constipation	33.3% 7/21 • 1 year treatment, 1year post treatment	40.9% 9/22 • 1 year treatment, 1year post treatment
Gastrointestinal disorders Diarrhea	47.6% 10/21 • 1 year treatment, 1year post treatment	40.9% 9/22 • 1 year treatment, 1year post treatment
Gastrointestinal disorders Distension	14.3% 3/21 • 1 year treatment, 1year post treatment	13.6% 3/22 • 1 year treatment, 1year post treatment
Gastrointestinal disorders Dry Mouth	28.6% 6/21 • 1 year treatment, 1year post treatment	40.9% 9/22 • 1 year treatment, 1year post treatment
Gastrointestinal disorders Flatulence	61.9% 13/21 • 1 year treatment, 1year post treatment	59.1% 13/22 • 1 year treatment, 1year post treatment
Gastrointestinal disorders Stomachache	38.1% 8/21 • 1 year treatment, 1year post treatment	27.3% 6/22 • 1 year treatment, 1year post treatment
Gastrointestinal disorders Nausea	28.6% 6/21 • 1 year treatment, 1year post treatment	27.3% 6/22 • 1 year treatment, 1year post treatment
Gastrointestinal disorders Vomiting	9.5% 2/21 • 1 year treatment, 1year post treatment	4.5% 1/22 • 1 year treatment, 1year post treatment
Nervous system disorders Dizziness	28.6% 6/21 • 1 year treatment, 1year post treatment	31.8% 7/22 • 1 year treatment, 1year post treatment
Nervous system disorders Headache	14.3% 3/21 • 1 year treatment, 1year post treatment	22.7% 5/22 • 1 year treatment, 1year post treatment
Nervous system disorders Mood Alteration	33.3% 7/21 • 1 year treatment, 1year post treatment	31.8% 7/22 • 1 year treatment, 1year post treatment
Nervous system disorders Tremor	23.8% 5/21 • 1 year treatment, 1year post treatment	4.5% 1/22 • 1 year treatment, 1year post treatment
General disorders Insomnia	42.9% 9/21 • 1 year treatment, 1year post treatment	22.7% 5/22 • 1 year treatment, 1year post treatment
General disorders Others	81.0% 17/21 • 1 year treatment, 1year post treatment	45.5% 10/22 • 1 year treatment, 1year post treatment