Sulforaphane for Chemotherapy-Related Cardiotoxicity

Overseen By sharda p singh

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Texas Tech University Health Sciences Center

Must be taking: Doxorubicin

Must not be taking: Beta blockers, Anti-arrhythmics

Disqualifiers: Diabetes, Hypertension, Myocardial infarction, others

Stay on Your Current Meds You can continue your current medications while participating

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 12 weeks

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether sulforaphane, a compound in broccoli sprouts, can protect the heart from damage caused by doxorubicin, a common breast cancer chemotherapy drug. The goal is to determine if sulforaphane can reduce heart-related side effects without compromising the chemotherapy's cancer-fighting ability. Participants will receive either sulforaphane or a placebo (a pill with no active ingredient) for 12 weeks. This trial may suit breast cancer patients undergoing doxorubicin treatment who have no history of heart disease. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially heart-protective treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications known to have cardiac effects, such as beta blockers, anti-arrhythmic agents, certain calcium channel blockers, ACE inhibitors, NSAIDs, and diuretics.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sulforaphane, a natural compound in broccoli, is generally safe for people. Various clinical trials have tested it for conditions like cancer, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). These studies found that sulforaphane is well-tolerated and does not cause serious side effects.

Moreover, research suggests that sulforaphane not only enhances the effectiveness of doxorubicin, a chemotherapy drug, in fighting cancer but also helps protect the heart from the drug's harmful effects. This dual action makes it a promising option for reducing heart damage in patients receiving chemotherapy.

Overall, while clinical trials continue to study sulforaphane, current research supports its safety and potential benefits when used with doxorubicin. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for chemotherapy-related cardiotoxicity, which often involve managing symptoms with medications like beta-blockers and ACE inhibitors, sulforaphane is derived from broccoli sprouts and offers a novel approach by potentially reducing heart damage at the cellular level. Researchers are excited about sulforaphane because it harnesses a natural compound known for its antioxidant properties, which may help protect heart cells during chemotherapy. This treatment is unique as it targets oxidative stress, a key factor in cardiotoxicity, rather than just addressing the symptoms, offering hope for a more proactive strategy in managing heart health during cancer treatment.

What evidence suggests that sulforaphane might be an effective treatment for chemotherapy-related cardiotoxicity?

This trial will evaluate the effects of sulforaphane on chemotherapy-related cardiotoxicity. Studies have shown that sulforaphane, a compound found in broccoli, works well with the chemotherapy drug doxorubicin. It enhances the effectiveness of the cancer drug and protects the heart from treatment-related damage. Research indicates that sulforaphane activates certain protective genes in the body, potentially reducing heart problems during cancer treatment. Early animal studies suggested it improved survival rates and boosted doxorubicin's ability to shrink tumors. These findings suggest that sulforaphane might make cancer treatment both safer and more effective. Participants in this trial will receive either sulforaphane or a placebo to assess its potential benefits. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

Adults aged 18-89 with breast cancer needing DOX treatment, without prior heart disease, diabetes, hypertension or myocardial infarction. Must not be pregnant/breastfeeding and willing to use birth control if of childbearing age. Participants should be able to swallow caplets and provide blood samples.

Inclusion Criteria

I can swallow up to 8 pills daily.

I have never been diagnosed with heart or artery disease.

I am a woman aged 18-50 and will use birth control during the study.

Exclusion Criteria

Inability to provide informed consent.

I cannot receive anthracycline treatment due to heart issues.

You regularly take supplements that contain antioxidants from fruits or vegetables, but it's okay if you take daily vitamin pills.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive DOX chemotherapy with or without sulforaphane for 12 weeks

12 weeks

4 visits (in-person) for DOX infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cardiac function and tumor size

1 year

Regular follow-up visits

Biomarker Assessment

Blood samples are collected to assess biomarkers of cardiotoxicity and gene expression

Throughout treatment

At each treatment cycle

What Are the Treatments Tested in This Trial?

Interventions

• Sulforaphane

Trial Overview The trial is testing whether the nutritional supplement sulforaphane can protect against heart damage caused by the chemotherapy drug doxorubicin in breast cancer patients, without affecting its anti-cancer effectiveness.

How Is the Trial Designed?

Group I: sulforaphane Active Control 1 Intervention

Processed SFN-rich extract will be purchased in form of caplets from Nutramax Laboratories, Inc. 2208 Lakeside Blvd Edgewood, MD 21040. Caplets containing SFN-rich broccoli sprout extracts from Nutramax Labs will be dispensed to participants in sealed bottles with instructions to keep them in a household freezer. Size of the caplet will be about 2 cm in length. Dosing will be based on weight and will be dosed daily for 12 weeks.

Group II: Placebo Placebo Group 1 Intervention

Placebo caplets will comprise of microcrystalline cellulose from Nutramax Labs and will be dispensed to participants in sealed bottles with instructions to keep them in a household freezer. Placebo pills will be identical in appearance to the sulforaphane pills and will be dosed in a similar manner (identical number of pills based on weight, daily dosing and for 12 weeks)

Who Is Running the Clinical Trial?

Texas Tech University Health Sciences Center

Lead Sponsor

Trials

107

Recruited

11,500+

Published Research Related to This Trial

Sulforaphane (SUL), derived from broccoli, effectively inhibits the proliferation of MCF-7 breast cancer cells by inducing G2/M cell cycle arrest and increasing cyclin B1 protein levels, demonstrating its potential as a cancer treatment.

The mechanism of action for SUL includes disrupting normal tubulin polymerization, which is crucial for cell division, thereby suggesting that it can suppress mammary cancer growth through effects on microtubule dynamics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization. Jackson, SJ., Singletary, KW.[2023]

Sulforaphane, derived from cruciferous vegetables like broccoli, shows promising anticancer properties by targeting tumor cells with stem cell-like characteristics, which may help prevent cancer relapse and resistance.

It works through multiple mechanisms, including inhibiting harmful enzymes that activate carcinogens and promoting processes like apoptosis and cell cycle arrest, making it a potential candidate for cancer prevention and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition. Tortorella, SM., Royce, SG., Licciardi, PV., et al.[2021]

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]

Sulforaphane (SFN) enhances the effectiveness of doxorubicin (DOX) in reducing breast cancer tumor growth, allowing for a lower dosage of DOX to be used, which could improve treatment outcomes.

SFN protects heart cells from the toxic effects of DOX by activating the Nrf2 pathway, reducing oxidative stress, and maintaining mitochondrial function, highlighting its potential as a cardioprotective agent during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulforaphane potentiates anticancer effects of doxorubicin and attenuates its cardiotoxicity in a breast cancer model. Bose, C., Awasthi, S., Sharma, R., et al.[2023]

In a study with male F344 rats, glucoraphanin from broccoli was found to be absorbed intact into the bloodstream, with 5% of the administered dose appearing in urine, indicating its bioavailability.

The study also revealed that glucoraphanin undergoes enterohepatic circulation and is hydrolyzed in the gut, leading to the production of various metabolites, including the beneficial compound sulforaphane.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The metabolic fate of purified glucoraphanin in F344 rats. Bheemreddy, RM., Jeffery, EH.[2022]

Sulforaphane (SUL), derived from broccoli, inhibits angiogenesis by suppressing the proliferation of endothelial cells, as shown in both in vitro studies with bovine aortic endothelial cells and in vivo studies with mice.

At a concentration of 15 microM, SUL caused cell cycle arrest in endothelial cells and disrupted microtubule polymerization, indicating its potential as a chemopreventive agent against cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulforaphane suppresses angiogenesis and disrupts endothelial mitotic progression and microtubule polymerization. Jackson, SJ., Singletary, KW., Venema, RC.[2022]

In a clinical trial with 50 healthy participants, sulforaphane was found to be significantly more bioavailable from a sulforaphane-rich beverage (SFR) compared to a glucoraphanin-rich beverage (GRR), with urinary excretion rates of 70% for SFR versus only 5% for GRR.

The study suggests that combining both SFR and GRR in future formulations could optimize dosing, allowing for both immediate and prolonged effects of sulforaphane, which may enhance its protective actions against cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability of Sulforaphane from two broccoli sprout beverages: results of a short-term, cross-over clinical trial in Qidong, China. Egner, PA., Chen, JG., Wang, JB., et al.[2022]

Sulforaphane (SFN) from broccoli can inhibit the growth of human colon carcinoma cells, showing a biphasic effect where short exposure leads to temporary cell cycle arrest, while longer exposure (at least 12 hours) results in permanent arrest and apoptosis.

The study found that low concentrations of SFN initially decrease glutathione levels but later induce its production, suggesting that this mechanism is linked to reversible cell cycle arrest rather than apoptosis, enhancing our understanding of how SFN works against cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biphasic modulation of cell proliferation by sulforaphane at physiologically relevant exposure times in a human colon cancer cell line. Pappa, G., Bartsch, H., Gerhäuser, C.[2021]

Sulforaphane, a compound found in broccoli, effectively induces cell cycle arrest and apoptosis in human lung adenocarcinoma cells, demonstrating its potential as an anti-cancer agent.

In a mouse model, intraperitoneal injection of sulforaphane significantly reduced tumor growth by over 70% compared to control, indicating its efficacy in inhibiting cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulforaphane induces cell-cycle arrest and apoptosis in cultured human lung adenocarcinoma LTEP-A2 cells and retards growth of LTEP-A2 xenografts in vivo. Liang, H., Lai, B., Yuan, Q.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03934905

Study Details | NCT03934905 | Protective Effects of the ... Hence, SFN may improve the clinical outcome of cancer therapy by (1) attenuating DOX cardiotoxicity and (2) enhancing the effects of cancer treatment on the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6804255/

Broccoli or Sulforaphane: Is It the Source or Dose That ... Broccoli-based glucoraphanin/sulforaphane-rich preparations have been shown to accelerate the detoxication and excretion of potentially carcinogenetic food ...

3. frontiersin.org frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2025.1601366/pdf

a review of the neuroprotective mechanisms of sulforaphane Among the trials focusing on neurological outcomes, ASD has been the most extensively studied condition (6 clinical trials detailed in Table 1).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5843244/

Sulforaphane potentiates anticancer effects of doxorubicin ... These studies indicate that SFN not only acts synergistically with DOX in cancer regression, but also protects the heart from DOX toxicity.

5. mdpi.com mdpi.com/2072-6694/13/19/4796

Sulforaphane: A Broccoli Bioactive Phytocompound with ... Sulforaphane (SFN) is a metabolite of the phytochemical glucoraphanin, which is found in high abundance in cruciferous vegetables, such as broccoli, watercress ...

6. withpower.com withpower.com/trial/phase-2-cardiotoxicity-11-2019-733e1

Sulforaphane for Chemotherapy-Related Cardiotoxicity Sulforaphane, a compound found in broccoli, is unique because it not only helps protect the heart from damage caused by chemotherapy drugs like doxorubicin but ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2211715625000426

Sulforaphane in alternative cancer chemotherapy This review focuses on SFN's role in cancer treatment, emphasizing its biological mechanisms and ability to regulate drug resistance.

8. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/74/NCT05153174/Prot_SAP_000.pdf

Safety, Feasibility and Efficacy of Sulforaphane (Avmacol ... SFN is currently in clinical trials for cancer of the breast, lung, and prostate, as well as autism and schizophrenia, and cardiotoxicity from chemotherapy ( ...