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Broccoli Sprout/Broccoli Seed Extract Supplement in Decreasing Toxicity in Heavy Smokers

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ClinicalTrials.gov Identifier: NCT03402230
Recruitment Status : Recruiting
First Posted : January 18, 2018
Last Update Posted : July 31, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This randomized early phase I trial studies how well broccoli sprout/broccoli seed extract supplement works in decreasing toxicity in heavy smokers. Broccoli sprout/broccoli seed extract supplement is a dietary supplement made from broccoli sprout and seed extract powder, and may break down some of the cancer causing substances in tobacco smoke and produce substances that may protect cells from tobacco smoke-induced damage in current smokers.

Condition or disease Intervention/treatment Phase
Current Every Day Smoker Tobacco Smoking Drug: Broccoli Sprout/Broccoli Seed Extract Supplement Other: Laboratory Biomarker Analysis Other: Questionnaire Administration Early Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine whether broccoli sprout/broccoli seed extract supplement (Avmacol) increases the urinary excretion of the mercapturic acid of the tobacco carcinogen, benzene, in healthy volunteers who are current heavy smokers.

SECONDARY OBJECTIVES:

I. To determine whether Avmacol increases the urinary excretion of the mercapturic acids of other tobacco carcinogens, including acrolein and crotonaldehyde.

II. To determine whether Avmacol increases the urinary excretion of the mercapturic acids of tobacco carcinogens, normalized by bio-measurement of tobacco exposure.

III. To determine whether Avmacol upregulates the NRF2 target gene transcripts in the buccal cells of current smokers.

IV. To evaluate for a dose-response relationship between Avmacol and the detoxification of tobacco carcinogens and the expression of NRF2 target gene transcripts.

V. To determine the relationship between systemic study agent exposure and biomarker modulation.

TERTIARY OBJECTIVES:

I. To determine whether the GSTM1 and GSTT1 genotypes are important genetic modulators of detoxification of tobacco carcinogens with Avmacol treatment.

II. To bank specimens for future research including evaluation of tobacco gene signatures in buccal and nasal epithelium and buccal cell nuclear morphometry.

OUTLINE: Participants are randomized into 1 of 2 arms.

ARM I: Participants receive lower dose broccoli sprout/broccoli seed extract supplement orally (PO) daily for 10-14 days. After 10-14 days, participants receive higher dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days.

ARM II: Participants receive higher dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days. After 10-14 days, participants receive lower dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days.

After completion of study, participants are followed up at 10-14 days.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 61 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Clinical Study of Avmacol® for Detoxification of Tobacco Carcinogens in Heavy Smokers
Actual Study Start Date : February 20, 2018
Estimated Primary Completion Date : November 30, 2020
Estimated Study Completion Date : November 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm I (Avmacol lower dose, Avmacol higher dose)
Participants receive lower dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days. After 10-14 days, participants receive higher dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days.
Drug: Broccoli Sprout/Broccoli Seed Extract Supplement
Given PO
Other Name: Avmacol

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Questionnaire Administration
Ancillary studies

Experimental: Arm II (Avmacol higher dose, Avmacol lower dose)
Participants receive higher dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days. After 10-14 days, participants receive lower dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days.
Drug: Broccoli Sprout/Broccoli Seed Extract Supplement
Given PO
Other Name: Avmacol

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Change in urinary excretion of the mercapturic acid of benzene [ Time Frame: Baseline up to 14 days post intervention ]
    The changes following 4 tablets of broccoli sprout/broccoli seed extract per day and after 8 tablets of broccoli sprout/broccoli seed extract per day will be determined separately. Two-sided paired t tests will be performed to evaluate whether the changes are significantly. Bonferroni correction will be used to correct for multiple comparisons (two dose levels).


Secondary Outcome Measures :
  1. Changes in the urinary excretion of the mercapturic acids of acrolein and crotonaldehyde [ Time Frame: Baseline up to 14 days post intervention ]
    The changes following 4 tablets of broccoli sprout/broccoli seed extract per day and after 8 tablets of broccoli sprout/broccoli seed extract l per day will be determined separately. Two-sided paired t tests will be performed to evaluate whether the changes are significantly. Bonferroni correction will be used to correct for multiple comparisons (two dose levels).

  2. Urinary excretion of the mercapturic acids of tobacco carcinogens [ Time Frame: Up to 14 days post intervention ]
    Will determine whether broccoli sprout/broccoli seed extract supplement increases the urinary excretion of the mercapturic acids of tobacco carcinogens, normalized by bio-measurement of tobacco exposure. Bio-measurement of tobacco exposure will be assessed by the total urinary levels of nicotine and major nicotine metabolites (i.e., the sum of the molar concentrations of nicotine and major nicotine metabolites in urine).

  3. Change in the NRF2 target gene transcripts [ Time Frame: Baseline up to 14 days post intervention ]
    Will be assessed by the expression of NQO1, in the buccal cells after intervention.

  4. Detoxification of tobacco carcinogens [ Time Frame: Up to 14 days post intervention ]
    Will determine whether there is a dose-response relationship between the broccoli sprout/broccoli seed extract supplement dose and the detoxification of tobacco carcinogens and the change in the NRF2 target gene transcripts.

  5. Systemic study agent exposure [ Time Frame: Up to 14 days post intervention ]
    Will determine the relationship between systemic study agent exposure, assessed by the total urinary levels of sulforaphane and its glutathione-derived metabolites (i.e., the sum of the molar concentrations of sulforaphane and its glutathione-derived metabolites in urine), and changes in detoxification of tobacco carcinogens and NRF2 target gene transcripts.


Other Outcome Measures:
  1. GSTM1 and GSTT1 genotypes [ Time Frame: Up to 14 days post intervention ]
    Will determine whether the GSTM1 and GSTT1 genotypes are important genetic modulators of detoxification of tobacco carcinogens. The change in the urinary excretion of the mercapturic acids of tobacco carcinogens will be compared between GSTM1-null and GSTM1 positive subjects and between GSTT1-null and GSTT1-positive subjects.

  2. Specimen banking [ Time Frame: Up to 14 days post intervention ]
    Will bank specimens for future research including tobacco gene signature in nasal brushing, and fixed buccal cells for nuclear morphometry.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Current tobacco smokers with >= 20 pack years of self-reported smoking exposure and a current average use of >= 10 cigarettes/day
  • Karnofsky performance scale >= 70%
  • Leukocytes >= 3,000/microliter
  • Absolute neutrophil count >= 1,500/microliter
  • Platelets >= 100,000/microliter
  • Total bilirubin =< 2 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x ULN
  • Creatinine =< ULN
  • Fertile subjects must use adequate contraception (abstinence, barrier methods, or birth control pills) prior to study entry and for the duration of study participation; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • History of invasive cancer within the past 2 years, with the exception of excised and cured non-melanoma skin cancer or carcinoma in situ of the cervix
  • Chronic, current or recent (within the past 2 weeks) use of systemic steroid doses equivalent to prednisone > 5 mg daily for continued use > 14 days; use of inhaled steroids, nasal sprays, and topical creams for small body areas is allowed
  • Participants may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Avmacol
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or lactating women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03402230


Locations
United States, Arizona
The University of Arizona Medical Center-University Campus Recruiting
Tucson, Arizona, United States, 85724
Contact: Julie E. Bauman    520-626-5972    jebauman@email.arizona.edu   
Principal Investigator: Julie E. Bauman         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Julie Bauman The University of Arizona Medical Center-University Campus

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03402230     History of Changes
Other Study ID Numbers: NCI-2017-02406
NCI-2017-02406 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
N01-CN-2012-00031
1711022046 ( Other Identifier: The University of Arizona Medical Center-University Campus )
UAZ2017-09-02 ( Other Identifier: DCP )
N01CN00031 ( U.S. NIH Grant/Contract )
P30CA023074 ( U.S. NIH Grant/Contract )
First Posted: January 18, 2018    Key Record Dates
Last Update Posted: July 31, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No