Evaluation of Broccoli Seed and Sprout Extract for Detoxification of Carcinogens in Firefighters

Malignant Solid Neoplasm Clinical Trial

Official title:

Phase II Randomized, Double-Blind, Placebo-Controlled, Crossover Trial of Broccoli Seed and Sprout Extract (BSSE) to Evaluate Detoxification of Carcinogens in Firefighters

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT06009926
• Other study ID #: NCI-2023-06404
• Secondary ID: NCI-2023-06404UA
• Status: Suspended
• Phase: Phase 2
• Start date: December 4, 2023
• Est. completion date: November 1, 2027

Study information

• Verified date: May 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial tests how well broccoli seed and sprout extract (BSSE) also called Avmacol extra strength (ES) works to help break down (detoxification) some of the cancer-causing chemicals (carcinogens) that firefighters are exposed to in order to help protect cells from smoke damage. Firefighters are routinely exposed to carcinogens during the course of their daily duties particularly from smoke exposure arising from active fire rescue, structural or incidental firefighting or burning, as well as flashover training. Flashover training simulator has been specifically designed for observation and recognition of fire behavior from rollover to flashover by varying fuel loading and altering ventilation. The simulator contains the fire behavior prop with smoke coming out and air being drawn in. All fires, including those in flashover training, release toxic and carcinogenic substances. These substances, many of which are known carcinogens, increase the risk of cancer in firefighters. Several studies to date have demonstrated that firefighters are at an increased risk of developing various malignancies including melanoma, multiple myeloma, acute myeloid leukemia, prostate, kidney, brain, and respiratory tract cancers among others. Broccoli extract has the potential to effectively enhance detoxification. This study may help researchers learn how BSSE can help break down chemicals that firefighters are exposed to during flashover training to help protect their cells from smoke-damage and reduce cancer risk.

Description:

PRIMARY OBJECTIVE:

I. To determine whether BSSE increases the urinary excretion of mercapturic acids of the flashover training carcinogen benzene in healthy, incumbent firefighters.

SEONDARY OBJECTIVES:

I. To evaluate whether BSSE increases urinary excretion of metabolites of polycyclic aromatic hydrocarbons (PAHs).

II. To evaluate the bioavailability of BSSE measured as sulforaphane (SF) metabolites and assess its association with BSSE-induced detoxification of carcinogens.

III. To evaluate the safety and tolerability of BSSE.

EXPLORATORY OBJECTIVES:

I. To determine whether the GSTM1 and GSTT1 genotypes are important genetic modulators of BSSE-induced detoxification of carcinogens.

II. To evaluate the effects of BSSE on flashover training-induced metabolomic changes.

OUTLINE: Participants are randomized to 1 of 2 groups.

GROUP I (BSSE-PLACEBO): Participants receive BSSE orally (PO) daily (QD) for 7-10 days then undergo the first flashover training between day 7-10 of agent intervention. Participants then receive placebo PO QD for 7-10 days then undergo second flashover training after a washout period of 2 weeks to 3 months. Participants also undergo urine sample collection throughout the study.

GROUP II (PLACEBO-BSSE): Participants receive placebo PO QD for 7-10 days then undergo the first flashover training between day 7-10 of agent intervention. Participants then receive BSSE for 7-10 days then undergo second flashover training after a washout period of 2 weeks to 3 months. Participants also undergo urine sample collection throughout the study.

After completion of study treatment, patients are followed up at 1-2 weeks.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 56
• Est. completion date: November 1, 2027
• Est. primary completion date: November 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female incumbent firefighters who are current non-smokers.

• Age >=18 years.

• Karnofsky performance scale >= 70%

• Absolute neutrophil count >= 1,000/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 glutamic-pyruvic transaminase [SGPT]) =< 3 x ULN

• Creatinine =< 1.5 x ULN

• Participants on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible.

• The effects of BSSE on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, 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, except for excised and cured nonmelanoma skin cancer or carcinoma in situ of the cervix. Participants who continue adjuvant treatment for an index cancer occurring > 2 years ago, such as adjuvant hormonal therapy for breast cancer, are excluded. Participants who are on anti-neoplastic treatment for a chronic malignancy, such as multiple myeloma or chronic myelogenous leukemia, are excluded.

• 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 (< 10% body surface area) 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 ES (BSSE).

• Uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnant or lactating women. Pregnant women are excluded from this study because the effects of BSSE on the developing human fetus are unknown. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with BSSE, breastfeeding should be discontinued if the mother is treated with BSSE.

• Participants with known human immunodeficiency virus (HIV), chronic hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Participants with human immunodeficiency virus (HIV), HBV and HCV are excluded from this study because there is no information regarding the impact of anti-viral drugs on the bioavailability of Avmacol ES. SF is known to modulate certain phase 1 and phase 2 enzymes involved in drug metabolism. The potential for SF to alter the metabolism (either by increasing or decreasing) of antiviral therapy could have an effect on the efficacy of the pharmaceuticals to keep viral titers low and the disease under control. Since many of the drugs used in therapies of these viral infections have extensive CYP450 enzymatic impact and BSSE has its own enzymatic properties, there is concern for drug-to-drug interactions.

• Ongoing use of any supplements containing active compounds in cruciferous vegetables such as SF and GR. The use of supplements related to the study agent may confound the study endpoints. Participant will be eligible if they agree to stop the SF or GR product at least 14 days prior to the intervention period 1, baseline visit

Related Conditions & MeSH terms

• Malignant Solid Neoplasm
• Neoplasms

Intervention

Procedure:
• Biospecimen Collection
Undergo urine sample collection

Dietary Supplement:
• Broccoli Sprout/Broccoli Seed Extract Supplement
Given PO

Drug:
• Placebo Administration
Given PO

Other:
• Questionnaire Administration
Ancillary studies
• Training
Undergo flashover training

Locations

Country	Name	City	State
United States	University of Arizona Cancer Center - Prevention Research Clinic	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Association of GSTM1 and GSTT1 genotypes with detoxification of benzene and/or PAHs	Will be assessed by a linear mixed effects model with random intercepts for changes in each of the log-transformed carcinogens, in which the fixed effects include BSSE, genotype, 2nd period indicator, and the sequence-specific 2nd period indicators and the interactions of BSSE and genotype indicators.	Post-intervention period 2
Other	Changes in untargeted urinary metabolomics	Will be measured by Exploris Orbitrap 480 for ultra-high performance liquid chromatography in two modes: electrospray ionisation mass spectrometry C18 (reverse phase) positive and hydrophilic interaction liquid chromatography negative, with standard quality control, filtering, and imputation procedures, will be calculated. A linear mixed effects model will be fitted to changes in log-transformed metabolomic levels. FDR will be controlled at 10% using an adjusted p-value approach (i.e. q-value).	Pre- and post- flashover training
Primary	Detoxification of benzene	Will be as assessed by changes in the urinary levels of the mercapturic acid of benzene, s-phenylmercapturic acid (SPMA) levels. Linear mixed effects model with random intercepts (i.e. subject specific intercept for each sequence) accounting for the within-subject correlation will be fitted to compare changes in log-transformed SPMA level between broccoli seed and sprout extract (BSSE) and placebo.	Baseline to post flashover training in each intervention period
Secondary	Detoxification of polyaromatic hydrocarbons (PAHs)	Will be measured by changes in the creatinine-normalized urinary levels of its metabolites including 1-hydroxypyrene. A linear mixed effects model will be fit to changes in log transformed PAH metabolite levels as performed for the primary endpoint. To account for multiple comparisons, false discovery rate (FDR) will be controlled at 10% using an adjusted p-value approach (i.e. q-value).	Baseline to post flashover training in each intervention period
Secondary	Bioavailability of BSSE	Will be as measured by urinary sulforophane (SF) metabolites.	Before the start of each intervention period and after each intervention period (collected after each flashover training)
Secondary	Relationship between urinary excretion of SF metabolites and detoxification of benzene and PAHs	Will be assessed by a linear mixed effects model with random intercepts, in which changes in each of the log-transformed carcinogens as the dependent variable (response) and changes in SF metabolites as the independent variable (dose).	Pre- to post-intervention
Secondary	Incidence of adverse events	Safety will be will be measured by adverse events (AE) classified in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events version 5. The frequency and associated percentage of each specific AE will be tabulated by the treatment sequence and then compared via Fisher's exact test. Each specific AE will be also tabulated by the treatment received (i.e., BSSE or placebo) and compared via McNemar's test. The tolerability will be measured by the adherence rate and will be compared between the BSSE and placebo via McNemar's test.	Post-intervention

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