Trial Outcomes & Findings for Phenethyl Isothiocyanate in Preventing Lung Cancer in Smokers (NCT NCT00691132)
NCT ID: NCT00691132
Last Updated: 2017-05-12
Results Overview
Urinary levels of Total ITC and PEITC-NAC by treatment sequence groups and treatment period.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
107 participants
Primary outcome timeframe
2 periods, 5 days each on PEITC or Placebo, with washout week between
Results posted on
2017-05-12
Participant Flow
Participant milestones
| Measure |
PEITC - Placebo (Short-term Trial)
Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month. Participants receive oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in week 2 and oral placebo four times daily for 5 days in week 4. Participants keep a diary of all food and beverages consumed on the days that PEITC or placebo are taken.
phenethyl isothiocyanate: Given orally
placebo: Given orally
|
Placebo - PEITC (Short-term Trial)
Participants receive oral placebo four times daily for 5 days in week 2 and oral PEITC four times daily for 5 days in week 4. Participants are also asked to smoke only deuterated NNK cigarettes, record the number of cigarettes smoked and alcoholic drinks consumed each day, and keep a food and beverage diary as in arm I.
phenethyl isothiocyanate: Given orally
placebo: Given orally
|
|---|---|---|
|
Overall Study
STARTED
|
53
|
54
|
|
Overall Study
COMPLETED
|
41
|
41
|
|
Overall Study
NOT COMPLETED
|
12
|
13
|
Reasons for withdrawal
| Measure |
PEITC - Placebo (Short-term Trial)
Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month. Participants receive oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in week 2 and oral placebo four times daily for 5 days in week 4. Participants keep a diary of all food and beverages consumed on the days that PEITC or placebo are taken.
phenethyl isothiocyanate: Given orally
placebo: Given orally
|
Placebo - PEITC (Short-term Trial)
Participants receive oral placebo four times daily for 5 days in week 2 and oral PEITC four times daily for 5 days in week 4. Participants are also asked to smoke only deuterated NNK cigarettes, record the number of cigarettes smoked and alcoholic drinks consumed each day, and keep a food and beverage diary as in arm I.
phenethyl isothiocyanate: Given orally
placebo: Given orally
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
3
|
|
Overall Study
Withdrawal by Subject
|
10
|
10
|
Baseline Characteristics
Phenethyl Isothiocyanate in Preventing Lung Cancer in Smokers
Baseline characteristics by cohort
| Measure |
PEITC - Placebo (Short-term Trial)
n=41 Participants
Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month. Participants receive oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in week 2 and oral placebo four times daily for 5 days in week 4. Participants keep a diary of all food and beverages consumed on the days that PEITC or placebo are taken.
phenethyl isothiocyanate: Given orally
placebo: Given orally
|
Placebo - PEITC (Short-term Trial)
n=41 Participants
Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month. Participants receive oral placebo four times daily for 5 days in week 2 and oral PEITC four times daily for 5 days in week 4. Participants are also asked to smoke only deuterated NNK cigarettes, record the number of cigarettes smoked and alcoholic drinks consumed each day, and keep a food and beverage diary as in arm I.
phenethyl isothiocyanate: Given orally
placebo: Given orally
|
Total
n=82 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
41 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
82 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
40.9 years
STANDARD_DEVIATION 10.6 • n=5 Participants
|
41.1 years
STANDARD_DEVIATION 9.6 • n=7 Participants
|
41.0 years
STANDARD_DEVIATION 10.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
44 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
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
55 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
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
41 participants
n=5 Participants
|
41 participants
n=7 Participants
|
82 participants
n=5 Participants
|
|
Body Mass Index
|
28.0 kg/m^2
STANDARD_DEVIATION 4.8 • n=5 Participants
|
28.0 kg/m^2
STANDARD_DEVIATION 6.3 • n=7 Participants
|
28.0 kg/m^2
STANDARD_DEVIATION 5.6 • n=5 Participants
|
|
Level of Education
High school or lower
|
14 participants
n=5 Participants
|
20 participants
n=7 Participants
|
34 participants
n=5 Participants
|
|
Level of Education
College or higher
|
27 participants
n=5 Participants
|
21 participants
n=7 Participants
|
48 participants
n=5 Participants
|
|
Current smoking rate
|
19.3 cigarettes/day
STANDARD_DEVIATION 6.6 • n=5 Participants
|
19.0 cigarettes/day
STANDARD_DEVIATION 6.7 • n=7 Participants
|
19.1 cigarettes/day
STANDARD_DEVIATION 6.6 • n=5 Participants
|
|
Cigarette smoking history
Years of smoking
|
14.7 years
STANDARD_DEVIATION 10.3 • n=5 Participants
|
17.9 years
STANDARD_DEVIATION 9.4 • n=7 Participants
|
16.3 years
STANDARD_DEVIATION 9.8 • n=5 Participants
|
|
Cigarette smoking history
Age at starting smoking
|
15.2 years
STANDARD_DEVIATION 4.9 • n=5 Participants
|
15.1 years
STANDARD_DEVIATION 4.6 • n=7 Participants
|
15.1 years
STANDARD_DEVIATION 4.7 • n=5 Participants
|
|
Cigarette smoking history
Age became regular smokers
|
18.6 years
STANDARD_DEVIATION 7.1 • n=5 Participants
|
17.7 years
STANDARD_DEVIATION 5.2 • n=7 Participants
|
18.1 years
STANDARD_DEVIATION 6.2 • n=5 Participants
|
|
Alcohol drinking
Never
|
14 participants
n=5 Participants
|
17 participants
n=7 Participants
|
31 participants
n=5 Participants
|
|
Alcohol drinking
Monthly or less
|
14 participants
n=5 Participants
|
12 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Alcohol drinking
Greater than monthly
|
12 participants
n=5 Participants
|
11 participants
n=7 Participants
|
23 participants
n=5 Participants
|
|
GSTM1 & GSTT1 genotypes
Both present
|
20 participants
n=5 Participants
|
18 participants
n=7 Participants
|
38 participants
n=5 Participants
|
|
GSTM1 & GSTT1 genotypes
Present/null
|
3 participants
n=5 Participants
|
4 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
GSTM1 & GSTT1 genotypes
Null/present
|
14 participants
n=5 Participants
|
11 participants
n=7 Participants
|
25 participants
n=5 Participants
|
|
GSTM1 & GSTT1 genotypes
Both null
|
4 participants
n=5 Participants
|
8 participants
n=7 Participants
|
12 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 periods, 5 days each on PEITC or Placebo, with washout week betweenUrinary levels of Total ITC and PEITC-NAC by treatment sequence groups and treatment period.
Outcome measures
| Measure |
PEITC-Placebo
n=41 Participants
Participants receive oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in Period 1 and oral placebo four times daily for 5 days in Period 2, with washout period in between. Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month.
|
Placebo - PEITC
n=41 Participants
Participants receive oral placebo four times daily for 5 days in Period 1 and oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in Period 2, with washout period in between. Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month.
|
GSTM1 and GSTT1 Both Genes Present
GSTM1 and GSTT1 Present: at least one allele positive for both glutathione-S-transferase (GST) M1 and T1, leading to higher enzymatic activity.
|
|---|---|---|---|
|
Urinary Levels of Biomarkers of NNK Metabolism
Period 1 - Total ITC
|
42.8 pmol/mg creatinine
Interval 37.4 to 48.9
|
0.36 pmol/mg creatinine
Interval 0.19 to 0.54
|
—
|
|
Urinary Levels of Biomarkers of NNK Metabolism
Period 2 - Total ITC
|
0.28 pmol/mg creatinine
Interval 0.13 to 0.46
|
49.7 pmol/mg creatinine
Interval 43.2 to 57.2
|
—
|
|
Urinary Levels of Biomarkers of NNK Metabolism
Period 1 - PEITC-NAC
|
56.7 pmol/mg creatinine
Interval 46.3 to 69.3
|
0.27 pmol/mg creatinine
Interval 0.08 to 0.48
|
—
|
|
Urinary Levels of Biomarkers of NNK Metabolism
Period 2 - PEITC-NAC
|
0.36 pmol/mg creatinine
Interval 0.01 to 0.85
|
68.1 pmol/mg creatinine
Interval 56.6 to 81.8
|
—
|
PRIMARY outcome
Timeframe: After 5 days of treatmentThe ratio of urinary \[pyridine-D4\]hydroxy acid : total \[pyridine-D4\]NNAL will be measured. This ratio is not expected to be influenced by the number of cigarettes smoked per day, or smoking topography.
Outcome measures
| Measure |
PEITC-Placebo
n=82 Participants
Participants receive oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in Period 1 and oral placebo four times daily for 5 days in Period 2, with washout period in between. Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month.
|
Placebo - PEITC
n=82 Participants
Participants receive oral placebo four times daily for 5 days in Period 1 and oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in Period 2, with washout period in between. Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month.
|
GSTM1 and GSTT1 Both Genes Present
GSTM1 and GSTT1 Present: at least one allele positive for both glutathione-S-transferase (GST) M1 and T1, leading to higher enzymatic activity.
|
|---|---|---|---|
|
Urinary Levels of Biomarkers of NNK Metabolism
Total [pyridine-D4]NNAL
|
0.366 pmol/mg creatinine
Interval 0.286 to 0.396
|
0.366 pmol/mg creatinine
Interval 0.285 to 0.396
|
—
|
|
Urinary Levels of Biomarkers of NNK Metabolism
[pyridine-D4]Hydroxy acid
|
0.150 pmol/mg creatinine
Interval 0.128 to 0.175
|
0.140 pmol/mg creatinine
Interval 0.12 to 0.163
|
—
|
|
Urinary Levels of Biomarkers of NNK Metabolism
[pyridine-D4]Hydroxy acid :[pyridine-D4]total NNAL
|
0.455 pmol/mg creatinine
Interval 0.409 to 0.508
|
0.420 pmol/mg creatinine
Interval 0.377 to 0.469
|
—
|
SECONDARY outcome
Timeframe: After 5 days of PEITC treatmentMeasured by high-performance liquid chromatography (HPLC). The aim is to determine the possible differential effects of GSTM1 genotype on PEITC excretion, using the method of Chung et al. The method will result in quantitative recovery of the PEITC-NAC.
Outcome measures
| Measure |
PEITC-Placebo
n=37 Participants
Participants receive oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in Period 1 and oral placebo four times daily for 5 days in Period 2, with washout period in between. Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month.
|
Placebo - PEITC
n=45 Participants
Participants receive oral placebo four times daily for 5 days in Period 1 and oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in Period 2, with washout period in between. Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month.
|
GSTM1 and GSTT1 Both Genes Present
GSTM1 and GSTT1 Present: at least one allele positive for both glutathione-S-transferase (GST) M1 and T1, leading to higher enzymatic activity.
|
|---|---|---|---|
|
Effects of GSTM1 Genotype on Phenethyl Isothiocyanate (PEITC)-NNK Association and on the Metabolism and Excretion of PEITC
PEITC-NAC
|
71.7 nmol/mg creatinine
Interval 58.6 to 87.6
|
54.8 nmol/mg creatinine
Interval 45.6 to 65.8
|
—
|
|
Effects of GSTM1 Genotype on Phenethyl Isothiocyanate (PEITC)-NNK Association and on the Metabolism and Excretion of PEITC
Total ITC
|
53.7 nmol/mg creatinine
Interval 46.7 to 61.8
|
40.5 nmol/mg creatinine
Interval 35.7 to 46.0
|
—
|
SECONDARY outcome
Timeframe: After 5 days of treatmentMeasured by high-performance liquid chromatography (HPLC). The aim is to determine the possible differential effects of GSTT1 genotype on PEITC excretion, using the method of Chung et al. The method will result in quantitative recovery of the PEITC-NAC.
Outcome measures
| Measure |
PEITC-Placebo
n=19 Participants
Participants receive oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in Period 1 and oral placebo four times daily for 5 days in Period 2, with washout period in between. Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month.
|
Placebo - PEITC
n=63 Participants
Participants receive oral placebo four times daily for 5 days in Period 1 and oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in Period 2, with washout period in between. Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month.
|
GSTM1 and GSTT1 Both Genes Present
GSTM1 and GSTT1 Present: at least one allele positive for both glutathione-S-transferase (GST) M1 and T1, leading to higher enzymatic activity.
|
|---|---|---|---|
|
Effects of GSTT1 Genotype on Phenethyl Isothiocyanate (PEITC)-NNK Association and on the Metabolism and Excretion of PEITC
PEITC-NAC
|
67.1 nmol/mg creatinine
Interval 50.3 to 89.6
|
60.4 nmol/mg creatinine
Interval 51.5 to 70.7
|
—
|
|
Effects of GSTT1 Genotype on Phenethyl Isothiocyanate (PEITC)-NNK Association and on the Metabolism and Excretion of PEITC
Total ITC
|
49.2 nmol/mg creatinine
Interval 40.0 to 60.4
|
45.1 nmol/mg creatinine
Interval 40.3 to 50.5
|
—
|
SECONDARY outcome
Timeframe: After 5 days of treatmentOutcome measures
| Measure |
PEITC-Placebo
n=12 Participants
Participants receive oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in Period 1 and oral placebo four times daily for 5 days in Period 2, with washout period in between. Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month.
|
Placebo - PEITC
n=32 Participants
Participants receive oral placebo four times daily for 5 days in Period 1 and oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in Period 2, with washout period in between. Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month.
|
GSTM1 and GSTT1 Both Genes Present
n=38 Participants
GSTM1 and GSTT1 Present: at least one allele positive for both glutathione-S-transferase (GST) M1 and T1, leading to higher enzymatic activity.
|
|---|---|---|---|
|
Combined Effects of GSTM1 and GSTT1 Genotype on Phenethyl Isothiocyanate (PEITC)-NNK Association and on the Metabolism and Excretion of PEITC
Total ITC
|
59.6 nmol/mg creatinine
Interval 46.3 to 76.5
|
47.1 nmol/mg creatinine
Interval 40.4 to 55.0
|
41.5 nmol/mg creatinine
Interval 36.1 to 47.8
|
|
Combined Effects of GSTM1 and GSTT1 Genotype on Phenethyl Isothiocyanate (PEITC)-NNK Association and on the Metabolism and Excretion of PEITC
PEITC-NAC
|
85.4 nmol/mg creatinine
Interval 59.7 to 122.2
|
60.5 nmol/mg creatinine
Interval 48.6 to 75.3
|
56.9 nmol/mg creatinine
Interval 46.6 to 69.6
|
SECONDARY outcome
Timeframe: After 5 days of treatment% Difference in ratio of urinary \[pyridine-D4\]hydroxy acid : total \[pyridine-D4\]NNAL while on PEITC compared to while on Placebo ((PEITC - Placebo) / PEITC) x 100%
Outcome measures
| Measure |
PEITC-Placebo
n=12 Participants
Participants receive oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in Period 1 and oral placebo four times daily for 5 days in Period 2, with washout period in between. Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month.
|
Placebo - PEITC
n=32 Participants
Participants receive oral placebo four times daily for 5 days in Period 1 and oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in Period 2, with washout period in between. Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month.
|
GSTM1 and GSTT1 Both Genes Present
n=38 Participants
GSTM1 and GSTT1 Present: at least one allele positive for both glutathione-S-transferase (GST) M1 and T1, leading to higher enzymatic activity.
|
|---|---|---|---|
|
Urinary Levels of [Pyridine-D4]Hydroxy Acid:Total [Pyridine-D4]NNAL Ratio by GSTM1 and GSTT1 Genotype.
|
-15.6 percentage of change in ratio
Interval -26.7 to -2.9
|
-3.1 percentage of change in ratio
Interval -14.6 to 9.9
|
-9.4 percentage of change in ratio
Interval -17.4 to -0.6
|
Adverse Events
Placebo (Short-term Trial)
Serious events: 0 serious events
Other events: 66 other events
Deaths: 0 deaths
Washout
Serious events: 0 serious events
Other events: 35 other events
Deaths: 0 deaths
PEITC (Short-term Trial)
Serious events: 0 serious events
Other events: 107 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo (Short-term Trial)
n=107 participants at risk
Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month. Participants receive oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in week 2 and oral placebo four times daily for 5 days in week 4. Participants keep a diary of all food and beverages consumed on the days that PEITC or placebo are taken.
phenethyl isothiocyanate: Given orally
placebo: Given orally
|
Washout
n=107 participants at risk
9 days between treatments
|
PEITC (Short-term Trial)
n=107 participants at risk
Participants receive oral placebo four times daily for 5 days in week 2 and oral PEITC four times daily for 5 days in week 4. Participants are also asked to smoke only deuterated NNK cigarettes, record the number of cigarettes smoked and alcoholic drinks consumed each day, and keep a food and beverage diary as in arm I.
phenethyl isothiocyanate: Given orally
placebo: Given orally
|
|---|---|---|---|
|
Gastrointestinal disorders
GI tract
|
28.0%
30/107 • Number of events 103
|
15.9%
17/107 • Number of events 35
|
57.9%
62/107 • Number of events 284
|
|
Nervous system disorders
Neurology
|
15.9%
17/107 • Number of events 35
|
7.5%
8/107 • Number of events 11
|
23.4%
25/107 • Number of events 58
|
|
General disorders
Constitutional
|
11.2%
12/107 • Number of events 24
|
5.6%
6/107 • Number of events 6
|
6.5%
7/107 • Number of events 13
|
|
General disorders
Other
|
6.5%
7/107 • Number of events 14
|
4.7%
5/107 • Number of events 5
|
12.1%
13/107 • Number of events 24
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place