Clinical trial NCT06009926: Evaluation of Broccoli Seed and Sprout Extract for Detoxification of Carcinogens in Firefighters
Official title: Phase II Randomized, Double-Blind, Placebo-Controlled Trial of Broccoli Seed and Sprout Extract (BSSE) to Evaluate Detoxification of Carcinogens in Firefighters
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Hematopoietic and Lymphatic System Neoplasm
Malignant Solid Neoplasm
Occupational Malignant Neoplasm
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2023-08-24
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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 \[SGPT\]) =\< 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change in total amount of acetaminophen mercapturate excreted in the urine
timeFrame: Baseline to end-of-intervention
Secondary outcomes:
measure: Change in total amount of acetaminophen glucuronide excreted in the urine
timeFrame: Baseline to end-of-intervention
measure: Incidence of adverse events
timeFrame: Start of intervention to follow-up
measure: Adherence rate
timeFrame: Up to 12 weeks
Other outcomes:
measure: GSTM1 and GSTT1 genotypes
timeFrame: Baseline to end-of-intervention
measure: Metabolomics
timeFrame: Baseline to end-of-intervention
measure: Mercapturic acid
timeFrame: Baseline to end-of-intervention
measure: Polycyclic aromatic hydrocarbons (PAHs)
timeFrame: Baseline to end-of-intervention
measure: Microribonucleic acid (microRNA)
timeFrame: Screening to end-of-intervention
measure: DNA methylation
timeFrame: Screening to end-of-intervention
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center - Prevention Research Clinic
state: Arizona
Study officials:
affiliation: University of Arizona Cancer Center - Prevention Research Clinic
name: Malvi Savani
role: PRINCIPAL_INVESTIGATOR
References: