Broccoli Extract for Tobacco-Related Cancer Risk
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: Anti-retrovirals, Anti-neoplastics
Disqualifiers: Invasive cancer, HIV, Hepatitis B, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This trial tests if an extract from broccoli seeds and sprouts can help heavy smokers by removing harmful substances from their bodies and protecting their cells from damage. Sulforaphane, derived from broccoli seeds and sprouts, has been shown to induce detoxification enzymes and protect against cancer.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you must stop using any supplements containing glucoraphanin or sulforaphane at least 7 days before starting the trial.
What data supports the effectiveness of the treatment Broccoli Sprout/Broccoli Seed Extract Supplement, Avmacol ES, Broccoli Seed and Sprout Extract, BSSE for reducing tobacco-related cancer risk?
Is broccoli extract safe for human use?
Broccoli sprout extracts, including those rich in glucoraphanin and sulforaphane, have been studied in humans and found to be generally safe with no significant adverse effects reported. Clinical trials have shown that these extracts are well-tolerated, with no consistent toxicities observed in participants.23678
How does the broccoli extract treatment differ from other treatments for tobacco-related cancer risk?
The broccoli extract treatment is unique because it uses natural compounds from broccoli sprouts and seeds, specifically glucoraphanin and sulforaphane, to help detoxify harmful substances found in tobacco smoke. Unlike traditional treatments, it focuses on enhancing the body's natural detoxification processes to reduce cancer risk.267910
Eligibility Criteria
This trial is for adult heavy smokers with a significant smoking history who are generally healthy. They must have normal blood counts, liver and kidney function, and if HIV or hepatitis positive, they need controlled viral loads. Women of childbearing age and men must use birth control during the study.Inclusion Criteria
Absolute neutrophil count >= 1,000/microliter
Ability to understand and the willingness to sign a written informed consent document
I am HIV positive, on treatment, and my viral load has been undetectable for the last 6 months.
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Exclusion Criteria
I haven't taken high doses of steroids recently, except for inhalers, nasal sprays, or small area creams.
I haven't had invasive cancer, except for certain skin cancers or cervical pre-cancers, in the last 2 years.
I am not pregnant or breastfeeding.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive broccoli seed and sprout extract or placebo orally once daily for 12 weeks. Blood, nasal epithelial cell, and buccal cell samples are collected throughout the study.
12 weeks
Visits at baseline, 2, 4, 8, and 12 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
2-4 weeks
Treatment Details
Interventions
- Broccoli Sprout/Broccoli Seed Extract Supplement (Phytochemical)
Trial OverviewThe trial is testing Avmacol ES (broccoli seed/sprout extract) to see if it helps break down harmful substances from tobacco in heavy smokers. Participants will either receive this supplement or a placebo while their biospecimens are collected for analysis.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Group I (broccoli seed and sprout extract)Experimental Treatment3 Interventions
Patients receive broccoli seed and sprout extract PO QD for 12 weeks in the absence of unacceptable toxicity. Patients undergo the collection of blood, nasal epithelial cell, and buccal cell samples throughout the study.
Group II: Group II (placebo)Active Control3 Interventions
Patients receive placebo PO QD for 12 weeks in the absence of unacceptable toxicity. Patients undergo the collection of blood, nasal epithelial cell, and buccal cell samples throughout the study.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Arizona Cancer Center - Prevention Research ClinicTucson, AZ
George Washington University Medical CenterWashington, United States
Roswell Park Cancer InstituteBuffalo, NY
University of British Columbia HospitalVancouver, Canada
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Effect of broccoli intake on markers related to oxidative stress and cancer risk in healthy smokers and nonsmokers. [2015]Cruciferous vegetables (CVs) have been widely studied for their anticarcinogenic properties. The aim of the present study was to evaluate the protective effect of broccoli intake in smokers and nonsmokers. Twenty young healthy males (10 smokers and 10 nonsmokers) were randomized in a cross-over design and received a portion of broccoli (200 g) or maintained a controlled diet for 10 days each. The two periods were separated by a wash-out period (20 days). Blood samples were collected at 0, 10, 30, and 40 days and used for the evaluation of DNA damage, insulin-like growth factor-I (IGF-I) and histone deacetylase (HDAC). Ex vivo protection from H(2)O(2)-induced DNA damage and endogenous DNA damage were evaluated in lymphocytes by means of the comet assay. Strand breaks decreased significantly after the broccoli diet in smokers as well as in nonsmokers (-22.2%; P
Randomized Crossover Trial Evaluating Detoxification of Tobacco Carcinogens by Broccoli Seed and Sprout Extract in Current Smokers. [2023]Consumption of cruciferous vegetables, rich in the isothiocyanate glucoraphanin, is associated with reduced risk of tobacco-related cancers. Sulforaphane, released by hydrolysis of glucoraphanin, potently induces cytoprotective phase II enzymes. Sulforaphane decreased the incidence of oral cancer in the 4NQO carcinogenesis model. In residents of Qidong, China, broccoli seed and sprout extracts (BSSE) increased detoxification of air pollutants benzene and acrolein, also found in tobacco smoke. This randomized, crossover trial evaluated detoxification of tobacco carcinogens by the BSSE Avmacol® in otherwise healthy smokers. Participants were treated for 2 weeks with both low and higher-dose BSSE (148 µmol vs. 296 µmol of glucoraphanin daily), separated by a 2-week washout, with randomization to low-high vs. high-low sequence. The primary endpoint was detoxification of benzene, measured by urinary excretion of its mercapturic acid, SPMA. Secondary endpoints included bioavailability, detoxification of acrolein and crotonaldehyde, modulation by GST genotype, and toxicity. Forty-nine participants enrolled, including 26 (53%) females with median use of 20 cigarettes/day. Low and higher-dose BSSE showed a mean bioavailability of 11% and 10%, respectively. Higher-dose BSSE significantly upregulated urinary excretion of the mercapturic acids of benzene (p = 0.04), acrolein (p
Broccoli or Sulforaphane: Is It the Source or Dose That Matters? [2021]There is robust epidemiological evidence for the beneficial effects of broccoli consumption on health, many of them clearly mediated by the isothiocyanate sulforaphane. Present in the plant as its precursor, glucoraphanin, sulforaphane is formed through the actions of myrosinase, a β-thioglucosidase present in either the plant tissue or the mammalian microbiome. Since first isolated from broccoli and demonstrated to have cancer chemoprotective properties in rats in the early 1990s, over 3000 publications have described its efficacy in rodent disease models, underlying mechanisms of action or, to date, over 50 clinical trials examining pharmacokinetics, pharmacodynamics and disease mitigation. This review evaluates the current state of knowledge regarding the relationships between formulation (e.g., plants, sprouts, beverages, supplements), bioavailability and efficacy, and the doses of glucoraphanin and/or sulforaphane that have been used in pre-clinical and clinical studies. We pay special attention to the challenges for better integration of animal model and clinical studies, particularly with regard to selection of dose and route of administration. More effort is required to elucidate underlying mechanisms of action and to develop and validate biomarkers of pharmacodynamic action in humans. A sobering lesson is that changes in approach will be required to implement a public health paradigm for dispensing benefit across all spectrums of the global population.
DNA damage and repair activity after broccoli intake in young healthy smokers. [2010]Cruciferous vegetables contain compounds with antioxidant properties (e.g. carotenoids, vitamin C and folates) and can alter the activity of xenobiotic metabolism (i.e. isothiocyanates). These constituents may be particularly important for subjects who are exposed to free radicals and genotoxic compounds, including smokers. The aim of the study was to evaluate the effect of broccoli intake on biomarkers of DNA damage and repair. Twenty-seven young healthy smokers consumed a portion of steamed broccoli (250 g/day) or a control diet for 10 days each within a crossover design with a washout period. Blood was collected before and after each period. The level of oxidatively damaged DNA lesions (formamidopyrimidine DNA glycosylase-sensitive sites), resistance to ex vivo H(2)O(2) treatment and repair of oxidised DNA lesions were measured in peripheral blood mononuclear cells (PBMCs). We also measured mRNA expression levels of repair and defence enzymes: 8-oxoguanine DNA glycosylase (OGG1), nucleoside diphosphate linked moiety X-type motif 1 (NUDT1) and heme oxygenase 1 (HO-1). After broccoli consumption, the level of oxidised DNA lesions decreased by 41% (95% confidence interval: 10%, 72%) and the resistance to H(2)O(2)-induced DNA strand breaks increased by 23% (95% CI: 13%, 34%). Following broccoli intake, a higher protection was observed in subjects with glutathione S-transferase (GST) M1-null genotype. The expression level and activity of repair enzymes was unaltered. In conclusion, broccoli intake was associated with increased protection against H(2)O(2)-induced DNA strand breaks and lower levels of oxidised DNA bases in PBMCs from smokers. This protective effect could be related to an overall improved antioxidant status.
Bioavailability and inter-conversion of sulforaphane and erucin in human subjects consuming broccoli sprouts or broccoli supplement in a cross-over study design. [2022]Broccoli consumption may reduce the risk of various cancers and many broccoli supplements are now available. The bioavailability and excretion of the mercapturic acid pathway metabolites isothiocyanates after human consumption of broccoli supplements has not been tested. Two important isothiocyanates from broccoli are sulforaphane and erucin. We employed a cross-over study design in which 12 subjects consumed 40 g of fresh broccoli sprouts followed by a 1 month washout period and then the same 12 subjects consumed 6 pills of a broccoli supplement. As negative controls for isothiocyanate consumption four additional subjects consumed alfalfa sprouts during the first phase and placebo pills during the second. Blood and urine samples were collected for 48h during each phase and analyzed for sulforaphane and erucin metabolites using LC-MS/MS. The bioavailability of sulforaphane and erucin is dramatically lower when subjects consume broccoli supplements compared to fresh broccoli sprouts. The peaks in plasma concentrations and urinary excretion were also delayed when subjects consumed the broccoli supplement. GSTP1 polymorphisms did not affect the metabolism or excretion of sulforaphane or erucin. Sulforaphane and erucin are able to interconvert in vivo and this interconversion is consistent within each subject but variable between subjects. This study confirms that consumption of broccoli supplements devoid of myrosinase activity does not produce equivalent plasma concentrations of the bioactive isothiocyanate metabolites compared to broccoli sprouts. This has implications for people who consume the recommended serving size (1 pill) of a broccoli supplement and believe they are getting equivalent doses of isothiocyanates.
Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I study. [2022]Broccoli sprouts are widely consumed in many parts of the world. There have been no reported concerns with respect to their tolerance and safety in humans. A formal phase I study of safety, tolerance, and pharmacokinetics appeared justified because these sprouts are being used as vehicles for the delivery of the glucosinolate glucoraphanin and its cognate isothiocyanate sulforaphane [1-isothiocyanato-(4R)-(methylsulfinyl)butane] in clinical trials. Such trials have been designed to evaluate protective efficacy against development of neoplastic and other diseases. A placebo-controlled, double-blind, randomized clinical study of sprout extracts containing either glucosinolates (principally glucoraphanin, the precursor of sulforaphane) or isothiocyanates (principally sulforaphane) was conducted on healthy volunteers who were in-patients on our clinical research unit. The subjects were studied in three cohorts, each comprising three treated individuals and one placebo recipient. Following a 5-day acclimatization period on a crucifer-free diet, the broccoli sprout extracts were administered orally at 8-h intervals for 7 days (21 doses), and the subjects were monitored during this period and for 3 days after the last treatment. Doses were 25 micromol of glucosinolate (cohort A), 100 micromol of glucosinolate (cohort B), or 25 micromol of isothiocyanate (cohort C). The mean cumulative excretion of dithiocarbamates as a fraction of dose was very similar in cohorts A and B (17.8 +/- 8.6% and 19.6 +/- 11.7% of dose, respectively) and very much higher and more consistent in cohort C (70.6 +/- 2.0% of dose). Thirty-two types of hematology or chemistry tests were done before, during, and after the treatment period. Indicators of liver (transaminases) and thyroid [thyroid-stimulating hormone, total triiodothyronine (T3), and free thyroxine (T4)] function were examined in detail. No significant or consistent subjective or objective abnormal events (toxicities) associated with any of the sprout extract ingestions were observed.
Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China. [2022]Epidemiological evidence has suggested that consumption of a diet rich in cruciferous vegetables reduces the risk of several types of cancers and chronic degenerative diseases. In particular, broccoli sprouts are a convenient and rich source of the glucosinolate, glucoraphanin, which can release the chemopreventive agent, sulforaphane, an inducer of glutathione S-transferases. Two broccoli sprout-derived beverages, one sulforaphane-rich (SFR) and the other glucoraphanin-rich (GRR), were evaluated for pharmacodynamic action in a crossover clinical trial design. Study participants were recruited from the farming community of He Zuo Township, Qidong, China, previously documented to have a high incidence of hepatocellular carcinoma with concomitant exposures to aflatoxin and more recently characterized with exposures to substantive levels of airborne pollutants. Fifty healthy participants were randomized into two treatment arms. The study protocol was as follows: a 5 days run-in period, a 7 days administration of beverage, a 5 days washout period and a 7 days administration of the opposite beverage. Urinary excretion of the mercapturic acids of acrolein, crotonaldehyde, ethylene oxide and benzene were measured both pre- and postinterventions using liquid chromatography tandem mass spectrometry. Statistically significant increases of 20-50% in the levels of excretion of glutathione-derived conjugates of acrolein, crotonaldehyde and benzene were seen in individuals receiving SFR, GRR or both compared with their preintervention baseline values. No significant differences were seen between the effects of SFR versus GRR. Intervention with broccoli sprouts may enhance detoxication of airborne pollutants and attenuate their associated health risks.
Inhibition of urinary bladder carcinogenesis by broccoli sprouts. [2022]Isothiocyanates are a well-known class of cancer chemopreventive agents, and broccoli sprouts are a rich source of several isothiocyanates. We report herein that dietary administration to rats of a freeze-dried aqueous extract of broccoli sprouts significantly and dose-dependently inhibited bladder cancer development induced by N-butyl-N-(4-hydroxybutyl) nitrosamine. The incidence, multiplicity, size, and progression of bladder cancer were all inhibited by the extract, while the extract itself caused no histologic changes in the bladder. Moreover, inhibition of bladder carcinogenesis by the extract was associated with significant induction of glutathione S-transferase and NAD(P)H:quinone oxidoreductase 1 in the bladder, enzymes that are important protectants against oxidants and carcinogens. Isothiocyanates are metabolized to dithiocarbamates in vivo, but dithiocarbamates readily dissociate to isothiocyanates. We found that >70% of the isothiocyanates present in the extract were excreted in the urine as isothiocyanate equivalents (isothiocyanates + dithiocarbamates) in 12 h after a single p.o. dose, indicating high bioavailability and rapid urinary excretion. In addition, the concentrations of isothiocyanate equivalents in the urine of extract-treated rats were 2 to 3 orders of magnitude higher than those in plasma, indicating that the bladder epithelium, the major site of bladder cancer development, is most exposed to p.o. dosed isothiocyanate. Indeed, tissue levels of isothiocyanate equivalents in the bladder were significantly higher than in the liver. In conclusion, broccoli sprout extract is a highly promising substance for bladder cancer prevention and the isothiocyanates in the extract are selectively delivered to the bladder epithelium through urinary excretion.
Modulation of plasma antioxidant levels, glutathione S-transferase activity and DNA damage in smokers following a single portion of broccoli: a pilot study. [2014]Broccoli is a rich source of bioactive compounds (i.e. glucosinolates, carotenoids, vitamin C and folate) that may exert an antioxidant effect and reduce oxidative damage. The objective of this pilot study was to investigate the effect of broccoli consumption on carotenoids, vitamin C and folate absorption, glutathione S-transferase (GST) activity, and oxidatively induced DNA damage in male smokers.
Broccoli (Brassica oleracea L. var. italica) Sprouts as the Potential Food Source for Bioactive Properties: A Comprehensive Study on In Vitro Disease Models. [2020]Broccoli sprouts are an excellent source of health-promoting phytochemicals such as vitamins, glucosinolates, and phenolics. The study aimed to investigate in vitro antioxidant, antiproliferative, apoptotic, and antibacterial activities of broccoli sprouts. Five-day-old sprouts extracted by 70% ethanol showed significant antioxidant activities, analyzed to be 68.8 μmol Trolox equivalent (TE)/g dry weight by 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic (ABTS) assay, 91% scavenging by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, 1.81 absorbance by reducing power assay, and high phenolic contents by high-performance liquid chromatography (HPLC). Thereafter, sprout extract indicated considerable antiproliferative activities towards A549 (lung carcinoma cells), HepG2 (hepatocellular carcinoma cells), and Caco-2 (colorectal adenocarcinoma cells) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, with IC50 values of 0.117, 0.168 and 0.189 mg/mL for 48 h, respectively. Furthermore, flow cytometry confirmed that Caco-2 cells underwent apoptosis by an increase of cell percentage in subG1 phase to 31.3%, and a loss of mitochondrial membrane potential to 19.3% after 48 h of treatment. Afterward, the extract exhibited notable antibacterial capacities against Bacillus subtilis and Salmonella Typhimurium with minimum inhibition concentration (MIC) values of 0.39 and 0.78 mg/mL, appropriately, along with abilities against Staphylococcus aureus and Escherichia coli with an MIC value of 1.56 mg/mL. Thus, broccoli sprouts were confirmed as a potential food source for consumers' selection and functional food industry.