Sulforaphane for Heart Failure

(CardiacAging Trial)

Overseen By Pooja Sethi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Texas Tech University Health Sciences Center

Must not be taking: Antioxidant supplements

Disqualifiers: Active cancer, Pulmonary issues, others

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

Compensation: Varies

Number of Visits: 5

Duration: 24 weeks

200 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 safely improve heart function in people with heart failure with preserved ejection fraction. This type of heart failure involves normal pumping but a stiff heart. Participants will take either sulforaphane or a placebo for 24 weeks to assess its effects on heart function and exercise endurance. Suitable candidates are those over 60 with heart failure symptoms but normal heart pumping, who can walk over 500 feet, and are willing to avoid other antioxidant supplements. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this novel treatment.

Will I have to stop taking my current medications?

The trial requires participants to avoid taking over-the-counter antioxidant supplements (like vegetable or fruit-containing supplement pills) during the study. It does not specify if you need to stop other medications, so you should discuss this with the trial team.

Is there any evidence suggesting that sulforaphane is likely to be safe for humans?

Research shows that sulforaphane, a compound found in broccoli sprouts, is generally safe for humans. Studies have not reported major safety concerns or side effects. Research indicates that people can consume sulforaphane without significant issues, meaning it is usually well-tolerated and should be safe for most individuals. However, individual reactions can vary with any treatment. It is important to consult a healthcare provider before starting any new treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Most treatments for heart failure focus on improving heart function or managing symptoms through medications like ACE inhibitors, beta-blockers, and diuretics. But sulforaphane (SFN), the active ingredient in this new treatment, offers a different approach. SFN is derived from broccoli sprouts and is believed to activate protective pathways in the body, potentially reducing oxidative stress and inflammation, which are key contributors to heart failure. Researchers are excited about SFN because it taps into the body's natural defenses rather than just managing symptoms, offering a novel way to tackle the root causes of heart failure. This unique mechanism could complement existing therapies and offer new hope for patients.

What evidence suggests that sulforaphane might be an effective treatment for heart failure?

Research has shown that sulforaphane, a substance in broccoli, may protect cells from damage. Studies have found that it can improve health by reducing oxidative stress, which is linked to many age-related conditions. In trials with individuals who have chronic kidney disease, sulforaphane slowed the disease and reduced stress markers in cells. Evidence also suggests that sulforaphane may protect the heart, particularly from damage caused by certain medications. This trial will evaluate sulforaphane's potential in managing heart failure by protecting heart cells and reducing damage. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for people over 60 with a type of heart failure where the heart muscle pumps well but is stiff (HFpEF). They must be able to walk more than 500 feet and agree not to take any antioxidant supplements during the study. It's not for those who can't consent, have active cancer, don't understand English well enough for the surveys, use oxygen therapy, or have walking issues due to lung or other problems.

Inclusion Criteria

I am older than 60 years.

I have heart failure symptoms but my heart's pumping ability is normal.

I can walk more than 500 feet by myself.

Exclusion Criteria

You cannot read and understand the SF-36 questionnaire in English.

I am currently using oxygen therapy.

I have been diagnosed with active cancer.

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 Sulforaphane (SFN) or placebo treatment for 24 weeks, with adherence monitored through pill counts

24 weeks

3 visits (in-person) at baseline, 12 weeks, and 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including echocardiography and exercise tests

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Sulforaphane

Trial Overview The trial tests if Sulforaphane (SFN), a compound found in vegetables like broccoli, can prevent age-related heart and blood vessel dysfunction. Participants will undergo echocardiograms and exercise endurance tests before and after taking SFN for 24 weeks to see if there's an improvement in their condition.

How Is the Trial Designed?

Group I: Avmacol ES Active Control 1 Intervention

Processed SFN-rich extract will be purchased from Nutramax Laboratories, Inc. 2208 Lakeside Blvd Edgewood, MD 21040. Caplets containing SFN-rich broccoli sprout extracts will be obtained from Nutramax Labs. Study medication will be dispensed in sealed bottles with instructions to keep them in a household freezer. The size of the caplet will be about the size of a 1000 mg Vit C pill (about 2 cm in length). The participants will be dosed, based on weight, in a double-blind fashion with identical appearing placebo or SFN caplets. Participants will be instructed to take a daily dose for 24 weeks based on the participants weight. Two caplets for individuals \<100 lb., three caplets for individuals 100-200 lb. and four caplets for individuals \>200 lb. SFN (Avmacol Extra Strength) will be prescribed by a study physician, and will be dispensed by the study coordinators at TTUHSC Lubbock. Pill counts will be conducted to demonstrate compliance.

Group II: Placebo Placebo Group 1 Intervention

Placebo caplets containing microcrystalline cellulose will be obtained from Nutramax Labs. Study medication will be dispensed in sealed bottles with instructions to keep them in a household freezer. The size of the caplet will be about the size of a 1000 mg Vit C pill (about 2 cm in length). The participants will be dosed, based on weight, in a double-blind fashion with identical appearing placebo or SFN caplets. Participants will be instructed to take a daily dose for 24 weeks based on the participants weight. Two caplets for individuals \<100 lb., three caplets for individuals 100-200 lb. and four caplets for individuals \>200 lb. Placebo will be prescribed by a study physician, and will be dispensed by the study coordinators at TTUHSC Lubbock. Pill counts will be conducted to demonstrate compliance.

Sulforaphane is already approved in United States for the following indications:

Approved in United States as Avmacol ES for:

• None approved; used in clinical trials for various conditions including chronic kidney disease and prevention of age-associated cardiac and vascular dysfunction

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

In a study involving 30 rabbits with chronic heart failure (CHF), treatment with sulforaphane (SFN) significantly improved heart function and structure after 12 weeks, as evidenced by better echocardiographic measurements and reduced heart weight ratios.

SFN treatment reduced markers of oxidative stress and inflammation, such as malondialdehyde (MDA) and inflammatory cytokines, indicating its potential as a therapeutic agent for improving cardiac health in CHF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulforaphane, a Natural Isothiocyanate Compound, Improves Cardiac Function and Remodeling by Inhibiting Oxidative Stress and Inflammation in a Rabbit Model of Chronic Heart Failure. Ma, T., Zhu, D., Chen, D., et al.[2021]

Sulforaphane, derived from cruciferous vegetables, effectively protects heart cells from hypertrophy induced by angiotensin II, as shown in experiments with H9c2 cells.

The protective effect of sulforaphane involves the inhibition of key signaling pathways, specifically Akt and NF-κB, which are associated with the development of cardiac hypertrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulforaphane protects H9c2 cardiomyocytes from angiotensin II-induced hypertrophy. Wu, QQ., Zong, J., Gao, L., et al.[2021]

Sulforaphane (SFN), a compound found in cruciferous vegetables, effectively suppresses cardiac hypertrophy in both laboratory and animal models by inhibiting the expression of fetal genes associated with heart enlargement.

The mechanism by which SFN prevents cardiac hypertrophy involves the downregulation of transcription factors GATA4/6 and the mitogen-activated protein kinase signaling pathways, suggesting its potential as a therapeutic agent for heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulforaphane suppresses cardiac hypertrophy by inhibiting GATA4/GATA6 expression and MAPK signaling pathways. Kee, HJ., Kim, GR., Kim, IK., et al.[2021]

Sulforaphane (SFN) significantly improves the survival of heart cells (cardiomyocytes) under conditions of low oxygen followed by reoxygenation, reducing cell death and apoptosis in a dose-dependent manner.

The protective effects of SFN are linked to the activation of the SIRT1 pathway, which helps inhibit cell death caused by endoplasmic reticulum (ER) stress, suggesting a potential therapeutic mechanism for cardiovascular protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulforaphane prevents rat cardiomyocytes from hypoxia/reoxygenation injury in vitro via activating SIRT1 and subsequently inhibiting ER stress. Li, YP., Wang, SL., Liu, B., 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]

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]

Nutraceuticals such as hawthorn, coenzyme Q10, and omega-3 fatty acids have shown potential benefits in improving heart function and quality of life in heart failure patients, particularly in the early stages of the disease.

These supplements are generally safe with minimal side effects and can be considered as complementary options alongside standard pharmacological treatments for heart failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutraceutical support in heart failure: a position paper of the International Lipid Expert Panel (ILEP). Cicero, AFG., Colletti, A., von Haehling, S., et al.[2021]

Broccoli is rich in glucoraphanin, which is converted to sulforaphane in the body, a compound known to induce phase II enzymes that may help in detoxifying harmful substances.

While there is strong evidence supporting sulforaphane's role in enzyme induction, the direct impact of broccoli on cancer prevention remains unclear, partly due to genetic variations in how individuals metabolize sulforaphane.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel concepts of broccoli sulforaphanes and disease: induction of phase II antioxidant and detoxification enzymes by enhanced-glucoraphanin broccoli. James, D., Devaraj, S., Bellur, P., et al.[2021]

Broccoli sprout supplements containing sulforaphane can potentially provide health benefits by activating the body's protective mechanisms through the Nrf2 pathway, but many available products lack the necessary enzyme activity for effective bioactivity.

Current labeling of broccoli sprout supplements often does not indicate whether they contain active myrosinase, which is crucial for converting glucoraphanin to sulforaphane, highlighting the need for better standardization and transparency in product labeling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulforaphane: translational research from laboratory bench to clinic. Houghton, CA., Fassett, RG., Coombes, JS.[2021]

Sulforaphane (SFN), derived from broccoli sprout extract, effectively protects against isoproterenol-induced myocardial injury in mice by restoring antioxidant levels and reducing oxidative stress, as shown in a study involving healthy male Swiss albino mice.

The treatment with SFN not only normalized biochemical parameters related to heart health but also showed protective effects in histopathological studies, indicating its potential as a cardioprotective agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulforaphane Attenuates Isoproterenol-Induced Myocardial Injury in Mice. Song, L., Srilakshmi, M., Wu, Y., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05797506

Safety, Feasibility and Efficacy of Sulforaphane (Avmacol ... The investigators hypothesize that daily intake of Avmacol ES can decrease kidney disease progression rate and decrease markers of oxidative stress and ...

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

Broccoli or Sulforaphane: Is It the Source or Dose That ... There is robust epidemiological evidence for the beneficial effects of broccoli consumption on health, many of them clearly mediated by the isothiocyanate ...

3. withpower.com withpower.com/trial/phase-2-renal-insufficiency-chronic-11-2021-a24cc

Study of Sulphoraphane in Chronic Kidney Disease This trial is testing sulforaphane, a compound that helps protect cells from damage, in patients with chronic kidney disease.

4. clinconnect.io clinconnect.io/trials/NCT05797506

Safety, Feasibility and Efficacy of Sulforaphane - ClinConnect This clinical trial is studying a supplement called Avmacol Extra Strength, which is made from broccoli seed extract, to see if it can help slow down the ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03934905

Study Details | NCT03934905 | Protective Effects of the ... The investigators propose to test an adjuvant therapy that combines the phytochemical sulforaphane (SFN) with DOX to attenuate DOX-induced cardiomyopathy.

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-06404

Evaluation of Broccoli Seed and Sprout Extract for ... This phase II randomized, placebo-controlled trial evaluates whether daily supplementation with broccoli seed and sprout extract (BSSE), also known as Avmacol ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2667031323000271

Beneficial role of broccoli and its active ingredient, ... Collectively, the data revealed that broccoli and sulforaphane have the potential to reduce hyperglycemia, hyperlipidemia, insulin resistance and ...