Phase II Randomized, Double-Blind, Placebo-Controlled Trial of Broccoli Seed and Sprout Extract (BSSE) to Evaluate Detoxification of Carcinogens in Firefighters
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Change in total amount of acetaminophen mercapturate excreted in the urine
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
盲法说明
Investigators and clinical research coordinators will avoid speculating with the participant regarding the participant's treatment group. The individual authorized to break the blind, if conditions are met, is the study principal investigator in consultation with the Division of Cancer Prevention medical monitor.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Group I (BSSE-placebo)
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)
干预措施: Questionnaire Administration (Other)
Group I (BSSE-placebo)
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)
干预措施: Training (Other)
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. (CLOSED TO ACCRUAL 10/07/2024)
干预措施: Biospecimen Collection (Procedure)
Group I (BSSE-placebo)
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)
干预措施: Biospecimen Collection (Procedure)
Group I (BSSE-placebo)
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)
干预措施: Placebo Administration (Drug)
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. (CLOSED TO ACCRUAL 10/07/2024)
干预措施: Placebo Administration (Drug)
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. (CLOSED TO ACCRUAL 10/07/2024)
干预措施: Training (Other)
Group III (BSSE, 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.
干预措施: Biospecimen Collection (Procedure)
Group IV (placebo, 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.
干预措施: Placebo Administration (Drug)
Group IV (placebo, 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.
干预措施: Questionnaire Administration (Other)
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. (CLOSED TO ACCRUAL 10/07/2024)
干预措施: Questionnaire Administration (Other)
Group III (BSSE, 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.
干预措施: Questionnaire Administration (Other)
Group IV (placebo, 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.
干预措施: Biospecimen Collection (Procedure)
Group I (BSSE-placebo)
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)
干预措施: Broccoli Sprout/Broccoli Seed Extract Supplement (Dietary Supplement)
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. (CLOSED TO ACCRUAL 10/07/2024)
干预措施: Broccoli Sprout/Broccoli Seed Extract Supplement (Dietary Supplement)
Group III (BSSE, 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.
干预措施: Acetaminophen (Drug)
Group III (BSSE, 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.
干预措施: Broccoli Sprout/Broccoli Seed Extract Supplement (Dietary Supplement)
Group IV (placebo, 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.
干预措施: Acetaminophen (Drug)
结局指标
主要结局
Change in total amount of acetaminophen mercapturate excreted in the urine
时间窗: 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.
次要结局
- Adherence rate(Up to 12 weeks)
- Change in total amount of acetaminophen glucuronide excreted in the urine(Baseline to end-of-intervention)
- Incidence of adverse events(Start of intervention to follow-up)