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 if a broccoli extract called Sulforaphane can help older adults with a certain type of heart failure. The extract may protect the heart by reducing damage and inflammation. Sulforaphane is a compound derived from vegetables like broccoli, known for its anti-inflammatory and antioxidant properties.

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 sulforaphane safe for human use?

Sulforaphane, found in broccoli and other cruciferous vegetables, has been studied for its health benefits, including antioxidant effects. While most research has been in animals or lab settings, over 50 clinical trials have examined its safety and effects in humans, suggesting it is generally safe when consumed in typical dietary amounts. ^{1 2 3 4 5}

How does the drug sulforaphane differ from other treatments for heart failure?

Sulforaphane is unique because it is a natural compound derived from cruciferous vegetables like broccoli and works by reducing oxidative stress and inflammation, which are key factors in heart failure. Unlike many traditional heart failure treatments, sulforaphane's antioxidant properties help improve heart function and prevent damage by boosting the body's own antioxidant defenses. ^{1 2 5 6 7}

What evidence supports the effectiveness of the treatment Sulforaphane for heart failure?

Research in rabbits shows that Sulforaphane can improve heart function and reduce heart damage by lowering stress and inflammation. Additionally, studies suggest that Sulforaphane, found in broccoli, may have health benefits, including for heart health, due to its ability to activate protective enzymes. ^{1 3 8 9 10}

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]

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) 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]

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]

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]

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), 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]

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), 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. United States 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. [2021]

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

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

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

Sulforaphane prevents rat cardiomyocytes from hypoxia/reoxygenation injury in vitro via activating SIRT1 and subsequently inhibiting ER stress. [2021]

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

Nutraceutical support in heart failure: a position paper of the International Lipid Expert Panel (ILEP). [2021]

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

Novel concepts of broccoli sulforaphanes and disease: induction of phase II antioxidant and detoxification enzymes by enhanced-glucoraphanin broccoli. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Sulforaphane protects H9c2 cardiomyocytes from angiotensin II-induced hypertrophy. [2021]

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

Sulforaphane: translational research from laboratory bench to clinic. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Sulforaphane suppresses cardiac hypertrophy by inhibiting GATA4/GATA6 expression and MAPK signaling pathways. [2021]

9. United States 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. [2022]

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

Sulforaphane Attenuates Isoproterenol-Induced Myocardial Injury in Mice. [2021]