Broccoli Extract for Tobacco-Related Cancer Risk

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anti-retrovirals, Anti-neoplastics

Disqualifiers: Invasive cancer, HIV, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

120 Participants Needed

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?

Research shows that broccoli and its extracts, like sulforaphane, can help detoxify harmful substances found in tobacco smoke and reduce DNA damage in smokers. This suggests that the treatment may lower cancer risk by enhancing the body's ability to repair and protect against damage. ^{1 2 3 4 5}

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. ^{2 3 6 7 8}

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. ^{2 6 7 9 10}

Research Team

Julie Bauman, MD

Principal Investigator

George Washington University Cancer Center

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.

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.

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

Trial Overview The 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

Group I: Group I (broccoli seed and sprout extract) Experimental Treatment 3 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 Control 3 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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study involving 20 young males (10 smokers and 10 nonsmokers), consuming 200 grams of broccoli significantly reduced DNA damage in both groups, with a notable 22.2% decrease in strand breaks (P < 0.0001).

Broccoli intake specifically led to a 51.0% reduction in oxidized purines in smokers (P < 0.0001), highlighting its protective effects against DNA damage, although it did not affect histone deacetylase (HDAC) activity or insulin-like growth factor-I (IGF-I) levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of broccoli intake on markers related to oxidative stress and cancer risk in healthy smokers and nonsmokers. Riso, P., Martini, D., Visioli, F., et al.[2015]

A randomized, crossover trial with 49 healthy smokers showed that broccoli seed and sprout extracts (BSSE) significantly increased the detoxification of tobacco-related carcinogens like benzene, acrolein, and crotonaldehyde, particularly at a higher dose of glucoraphanin.

The higher-dose BSSE led to a significant increase in the urinary excretion of mercapturic acids associated with these carcinogens, indicating enhanced detoxification, regardless of the participants' GST genotype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Crossover Trial Evaluating Detoxification of Tobacco Carcinogens by Broccoli Seed and Sprout Extract in Current Smokers. Bauman, JE., Hsu, CH., Centuori, S., et al.[2023]

Broccoli consumption, particularly due to the isothiocyanate sulforaphane derived from its precursor glucoraphanin, has been linked to health benefits, including cancer chemoprotection, supported by over 3000 studies and more than 50 clinical trials.

There is a need for improved integration of animal and human studies to better understand the effective doses and mechanisms of action of sulforaphane, as well as to develop reliable biomarkers for its effects in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Broccoli or Sulforaphane: Is It the Source or Dose That Matters? Yagishita, Y., Fahey, JW., Dinkova-Kostova, AT., et al.[2021]

In a study involving 27 young healthy smokers, consuming 250 g of steamed broccoli daily for 10 days significantly reduced oxidatively damaged DNA lesions by 41% and increased resistance to DNA damage from hydrogen peroxide by 23%.

The protective effects of broccoli intake were particularly notable in individuals with the GST M1-null genotype, suggesting that broccoli may enhance antioxidant status and DNA repair mechanisms in smokers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DNA damage and repair activity after broccoli intake in young healthy smokers. Riso, P., Martini, D., Møller, P., et al.[2010]

A study involving 12 subjects found that consuming broccoli supplements results in significantly lower bioavailability of the beneficial compounds sulforaphane and erucin compared to eating fresh broccoli sprouts.

The study highlights that broccoli supplements, which lack myrosinase activity, do not provide the same levels of bioactive isothiocyanates in the bloodstream, potentially misleading consumers about their health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability and inter-conversion of sulforaphane and erucin in human subjects consuming broccoli sprouts or broccoli supplement in a cross-over study design. Clarke, JD., Hsu, A., Riedl, K., et al.[2022]

A phase I clinical study involving healthy volunteers showed that broccoli sprout extracts containing glucoraphanin and sulforaphane were safe and well-tolerated, with no significant adverse effects reported during the treatment period.

The study demonstrated that the isothiocyanate sulforaphane was excreted at a much higher rate (70.6% of the dose) compared to glucosinolates, indicating effective absorption and potential for protective health benefits against diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I study. Shapiro, TA., Fahey, JW., Dinkova-Kostova, AT., et al.[2022]

A clinical trial involving 50 healthy participants showed that consuming broccoli sprout-derived beverages significantly increased the excretion of detoxified pollutants, indicating enhanced detoxification processes in the body.

Both sulforaphane-rich and glucoraphanin-rich beverages were effective in promoting the excretion of harmful substances like acrolein and benzene, suggesting that broccoli sprouts may help reduce health risks associated with airborne pollutants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China. Kensler, TW., Ng, D., Carmella, SG., et al.[2022]

A freeze-dried aqueous extract of broccoli sprouts significantly inhibited bladder cancer development in rats, showing a dose-dependent effect without causing any harmful changes to the bladder tissue.

The extract's effectiveness is linked to the induction of protective enzymes in the bladder and demonstrates high bioavailability, with isothiocyanates being rapidly excreted in urine, ensuring targeted delivery to the bladder epithelium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of urinary bladder carcinogenesis by broccoli sprouts. Munday, R., Mhawech-Fauceglia, P., Munday, CM., et al.[2022]

In a pilot study with 10 male smokers, consuming a single portion of steamed broccoli significantly increased plasma levels of vitamin C and folate by 35% and 70%, respectively, within 3 hours, and β-carotene by 8% within 6 hours.

Broccoli consumption also led to an 18% reduction in hydrogen peroxide-induced DNA damage in blood cells 24 hours later, particularly in individuals with the GSTM1 gene, highlighting its potential protective effects against oxidative stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of plasma antioxidant levels, glutathione S-transferase activity and DNA damage in smokers following a single portion of broccoli: a pilot study. Riso, P., Del Bo', C., Vendrame, S., et al.[2014]

Broccoli sprouts exhibit strong antioxidant properties, with significant activity measured through various assays, indicating their potential health benefits as a rich source of phytochemicals.

The extract from broccoli sprouts demonstrated effective antiproliferative and apoptotic effects on cancer cells, particularly A549, HepG2, and Caco-2, suggesting their potential role in cancer prevention or treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Broccoli (Brassica oleracea L. var. italica) Sprouts as the Potential Food Source for Bioactive Properties: A Comprehensive Study on In Vitro Disease Models. Le, TN., Luong, HQ., Li, HP., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effect of broccoli intake on markers related to oxidative stress and cancer risk in healthy smokers and nonsmokers. [2015]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Randomized Crossover Trial Evaluating Detoxification of Tobacco Carcinogens by Broccoli Seed and Sprout Extract in Current Smokers. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Broccoli or Sulforaphane: Is It the Source or Dose That Matters? [2021]

4. England pubmed.ncbi.nlm.nih.gov

DNA damage and repair activity after broccoli intake in young healthy smokers. [2010]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Bioavailability and inter-conversion of sulforaphane and erucin in human subjects consuming broccoli sprouts or broccoli supplement in a cross-over study design. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Inhibition of urinary bladder carcinogenesis by broccoli sprouts. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Modulation of plasma antioxidant levels, glutathione S-transferase activity and DNA damage in smokers following a single portion of broccoli: a pilot study. [2014]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Broccoli (Brassica oleracea L. var. italica) Sprouts as the Potential Food Source for Bioactive Properties: A Comprehensive Study on In Vitro Disease Models. [2020]