Evaluation of Broccoli Seed and Sprout Extract for Detoxification of Carcinogens in Firefighters
- Conditions
- Hematopoietic and Lymphatic System NeoplasmOccupational Malignant NeoplasmMalignant Solid Neoplasm
- Interventions
- Procedure: Biospecimen CollectionDietary Supplement: Broccoli Sprout/Broccoli Seed Extract SupplementDrug: Placebo AdministrationOther: Questionnaire AdministrationOther: Training
- Registration Number
- NCT06009926
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase II randomized, placebo-controlled trial evaluates whether daily supplementation with broccoli seed and sprout extract (BSSE), also known as Avmacol Extra Strength (ES), enhances the body's natural ability to detoxify carcinogens commonly encountered by firefighters. Firefighters are routinely exposed to harmful chemicals such as benzene and polycyclic aromatic hydrocarbons (PAHs) through smoke inhalation, structural fires, and fuel leak incidents exposures that contribute to their elevated cancer risk. BSSE contains bioactive compounds known to activate phase II detoxification enzymes that help eliminate reactive toxins from the body. A single dose of acetaminophen (Tylenol) is administered at both baseline and end-of-intervention as a metabolic probe to assess changes in detoxification enzyme activity. Acetaminophen is metabolized through the same pathways as benzene and PAHs, making it a useful surrogate for evaluating the effect of BSSE on the detoxification of fire-related toxicants. Participants were originally randomized into one of total four study groups. Groups I and II, now closed to accrual, were designed to assess BSSE effects before and after controlled flashover fire training exercises. These arms were discontinued after it was determined that training fires produced insufficient real-world toxicant exposure to evaluate the intervention's impact. Groups III and IV were subsequently open and represent the active phase of the study. Group III participants receive BSSE daily for 12 weeks, while Group IV participants receive a matched placebo. Both groups include acetaminophen challenge at baseline and end-of-intervention, with biospecimen collection to evaluate detoxification capacity and explore genetic and epigenetic modifiers of response. Although the protocol includes four study groups, only two are currently active. Groups I and II remain part of the study record but are closed and will not contribute to the primary outcome analyses.
- Detailed Description
PRIMARY OBJECTIVE:
I. To determine whether BSSE increases the urinary excretion of mercapturic acid of acetaminophen, a surrogate for detoxification of the carcinogen benzene in healthy, incumbent firefighters.
SECONDARY OBJECTIVES:
I. To evaluate the effects of BSSE on urinary excretion of acetaminophen glucuronide, a surrogate for detoxification of polycyclic aromatic hydrocarbons (PAHs).
II. 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 urinary metabolomics. III. To determine the effects of BSSE on the urinary excretion of the mercapturic acid of benzene after fire/fuel leak activities.
IV. To determine the effects of BSSE on the urinary excretion of metabolites of PAHs after fire/fuel leak activities.
V. To determine the effects of BSSE on epigenetic modifications (blood microribonucleic acid \[RNA\] and deoxyribonucleic acid \[DNA\] methylation).
OUTLINE: Participants are randomized to Group III or Group IV.
GROUP I (BSSE-PLACEBO) (CLOSED TO ACCRUAL 10/07/2024): 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) (CLOSED TO ACCRUAL 10/07/2024): 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.
GROUP III: Participants receive BSSE PO QD for 12 weeks on study. Participants also receive acetaminophen PO once prior to starting BSSE and once following completion of BSSE on study. Participants undergo blood and urine sample collection throughout the study.
GROUP IV: Participants receive placebo PO QD for 12 weeks on study. Participants also receive acetaminophen PO once prior to starting placebo and once following completion of placebo on study. Participants undergo blood and urine sample collection throughout the study.
After completion of study intervention, participants are followed up at 2 weeks.
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 66
- 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]) =< 2 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.
- History of invasive cancer within the past 2 years, except for excised and cured non-melanoma 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 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. Sulforaphane (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 glucoraphanin (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 baseline visit.
- History of allergic reactions to acetaminophen or the formulation ingredients or any other contraindication to acetaminophen use.
- Unwilling or unable to refrain from the use of non-study acetaminophen (or acetaminophen containing products) for 72 hours prior to the baseline evaluation of acetaminophen metabolism and for 72 hours prior to the end-of-intervention evaluation of acetaminophen metabolism.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group I (BSSE-placebo) Training Participants receive BSSE PO 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. (CLOSED TO ACCRUAL 10/07/2024) Group II (placebo-BSSE) Biospecimen Collection 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. (CLOSED TO ACCRUAL 10/07/2024) Group II (placebo-BSSE) Broccoli Sprout/Broccoli Seed Extract Supplement 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. (CLOSED TO ACCRUAL 10/07/2024) Group II (placebo-BSSE) Questionnaire Administration 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. (CLOSED TO ACCRUAL 10/07/2024) Group II (placebo-BSSE) Placebo Administration 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. (CLOSED TO ACCRUAL 10/07/2024) Group II (placebo-BSSE) Training 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. (CLOSED TO ACCRUAL 10/07/2024) Group III (BSSE, acetaminophen) Biospecimen Collection Participants receive BSSE PO QD for 12 weeks on study. Participants also receive acetaminophen PO once prior to starting BSSE and once following completion of BSSE on study. Participants undergo blood and urine sample collection throughout the study. Group III (BSSE, acetaminophen) Acetaminophen Participants receive BSSE PO QD for 12 weeks on study. Participants also receive acetaminophen PO once prior to starting BSSE and once following completion of BSSE on study. Participants undergo blood and urine sample collection throughout the study. Group IV (placebo, acetaminophen) Placebo Administration Participants receive placebo PO QD for 12 weeks on study. Participants also receive acetaminophen PO once prior to starting placebo and once following completion of placebo on study. Participants undergo blood and urine sample collection throughout the study. Group IV (placebo, acetaminophen) Questionnaire Administration Participants receive placebo PO QD for 12 weeks on study. Participants also receive acetaminophen PO once prior to starting placebo and once following completion of placebo on study. Participants undergo blood and urine sample collection throughout the study. Group III (BSSE, acetaminophen) Broccoli Sprout/Broccoli Seed Extract Supplement Participants receive BSSE PO QD for 12 weeks on study. Participants also receive acetaminophen PO once prior to starting BSSE and once following completion of BSSE on study. Participants undergo blood and urine sample collection throughout the study. Group III (BSSE, acetaminophen) Questionnaire Administration Participants receive BSSE PO QD for 12 weeks on study. Participants also receive acetaminophen PO once prior to starting BSSE and once following completion of BSSE on study. Participants undergo blood and urine sample collection throughout the study. Group IV (placebo, acetaminophen) Acetaminophen Participants receive placebo PO QD for 12 weeks on study. Participants also receive acetaminophen PO once prior to starting placebo and once following completion of placebo on study. Participants undergo blood and urine sample collection throughout the study. Group IV (placebo, acetaminophen) Biospecimen Collection Participants receive placebo PO QD for 12 weeks on study. Participants also receive acetaminophen PO once prior to starting placebo and once following completion of placebo on study. Participants undergo blood and urine sample collection throughout the study. Group I (BSSE-placebo) Biospecimen Collection Participants receive BSSE PO 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. (CLOSED TO ACCRUAL 10/07/2024) Group I (BSSE-placebo) Broccoli Sprout/Broccoli Seed Extract Supplement Participants receive BSSE PO 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. (CLOSED TO ACCRUAL 10/07/2024) Group I (BSSE-placebo) Placebo Administration Participants receive BSSE PO 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. (CLOSED TO ACCRUAL 10/07/2024) Group I (BSSE-placebo) Questionnaire Administration Participants receive BSSE PO 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. (CLOSED TO ACCRUAL 10/07/2024)
- Primary Outcome Measures
Name Time Method Change in total amount of acetaminophen mercapturate excreted in the urine Baseline to end-of-intervention Will compare after acetaminophen dosing between broccoli seed and sprout extract (BSSE) and placebo arms. Will be quantified by liquid chromatography tandem mass spectrometry. Log-transformation will be applied to total amount of acetaminophen mercapturate before deriving the changes at the end of intervention from baseline since the total amount of acetaminophen mercapturate may be highly right skewed. Even if the total amount of acetaminophen mercapturate is not highly right skewed, log-transformation will also allow comparison of the relative percent change in total amount of acetaminophen mercapturate at the end of intervention from baseline between the BSSE and placebo groups through use of the geometric mean of total amount of acetaminophen mercapturate. Will be analyzed in participants who initiated treatment and provided both pre-study agent intervention and post-study agent intervention urine.
- Secondary Outcome Measures
Name Time Method Adherence rate Up to 12 weeks Tolerability will be measured by adherence rate and will be compared between the BSSE and placebo via Fisher's exact test.
Change in total amount of acetaminophen glucuronide excreted in the urine Baseline to end-of-intervention Will compare after acetaminophen dosing between BSSE and placebo arms. Will be quantified by liquid chromatography tandem mass spectrometry.
Incidence of adverse events Start of intervention to follow-up Will evaluate safety of BSSE, as measured by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5. Toxicity will be measured by adverse events (AE) classified in accordance with NCI CTCAE version 5. The frequency and associated percentage of each specific AE will be tabulated by treatment group and then compared via Fisher's exact test. All participants will be evaluable for toxicity from the time of their first dose of BSSE versus placebo. Descriptive statistics of the type and frequency of all AEs will be generated, including 95% confidence intervals.
Trial Locations
- Locations (1)
University of Arizona Cancer Center - Prevention Research Clinic
🇺🇸Tucson, Arizona, United States
University of Arizona Cancer Center - Prevention Research Clinic🇺🇸Tucson, Arizona, United States