Sulforaphane for Chronic Kidney Disease

Overseen By Allison Stewart

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Rochester

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Cancer, Dementia, Heart failure, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 7 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of sulforaphane, a compound found in broccoli seed extract, which may boost antioxidant activity and reduce damage associated with chronic kidney disease. Participants will try different doses to determine the safest one for individuals with this condition. The trial suits those who have experienced a decline in kidney function over the past year, maintain controlled blood pressure, and can swallow pills. 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 new treatment.

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 have a stable blood pressure medication regimen for at least one month before starting the study.

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

Research has shown that sulforaphane is usually safe for most people. In studies, participants have safely taken sulforaphane-rich products for up to six months. Previous research found that taking four tablets a day is safe for people with chronic kidney disease. While sulforaphane has been tested in people with breast cancer who have healthy kidneys, this study will focus on its use in those with kidney disease. Overall, sulforaphane appears safe when used as a supplement. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney disease?

Researchers are excited about sulforaphane as a potential treatment for chronic kidney disease because it offers a novel approach compared to current treatments like ACE inhibitors or ARBs. Unlike these standard options that primarily focus on controlling blood pressure and reducing proteinuria, sulforaphane is a naturally occurring compound found in cruciferous vegetables and is believed to have antioxidant and anti-inflammatory properties. This could help protect kidney cells from damage and slow the progression of the disease. Furthermore, the treatment is being explored in different dosages, which could optimize its effectiveness and provide new insights into dosage-related outcomes.

What evidence suggests that sulforaphane might be an effective treatment for kidney disease?

Research shows that sulforaphane might slow kidney disease by reducing oxidative stress, which can damage cells. Studies with healthy individuals have demonstrated that sulforaphane increases the body's detoxification ability, aiding in the removal of harmful substances. This compound has been tested in patients with various conditions and has shown potential benefits in lowering disease markers. Although it hasn't been specifically tested in people with chronic kidney disease, its ability to boost antioxidant activity appears promising. Participants in this trial will take either 2 or 4 extra-strength tablets of sulforaphane daily to evaluate its effects on kidney health by activating the body's natural defenses. ^{1 2 6 7 8}

Who Is on the Research Team?

Thu H Le, MD, FAHA

Principal Investigator

Division of Nephrology Chief

Are You a Good Fit for This Trial?

Inclusion Criteria

You can swallow pills.

Blood pressure <140/90 mm Hg prior to initiation of sulphoraphane

eGFR ≥ 20 and <60 ml/min/m2/year, and a decline in eGFR of ≥ 3 ml/min/m2/year in the previous 12 months

Exclusion Criteria

New York Heart Association Class 3 or 4 heart failure symptoms, known EF ≤30% or hospital admission for heart failure within the past 3 months

You have high blood pressure that is not being managed or controlled.

Your doctor thinks there are things that might make it difficult for you to follow the treatment plan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily doses of sulforaphane (Avmacol Extra Strength) to establish a safe dose for patients with chronic kidney disease

7 days

Daily visits for pharmacokinetic measurements

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sulforaphane

How Is the Trial Designed?

Group I: 4 tablets of Sulforaphane Experimental Treatment 1 Intervention

Participants will be given 4 extra strength tablets per day

Group II: 2 tablets of Sulforaphane Experimental Treatment 1 Intervention

Participants will be given 2 extra strength tablets per day

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?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Sulforaphane (SFN) and broccoli leaf extract (BLE) significantly reduced lipid accumulation and triglyceride content in fat cells (3T3-L1 adipocytes) and improved metabolic markers in ob/ob mice, indicating their potential as anti-obesity agents.

The treatment with SFN and BLE not only decreased fat storage and improved liver health but also normalized the expression of 32 genes related to lipid metabolism, suggesting a mechanism of action that involves enhancing metabolic pathways in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-obesity effect of sulforaphane in broccoli leaf extract on 3T3-L1 adipocytes and ob/ob mice. Ranaweera, SS., Natraj, P., Rajan, P., et al.[2022]

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]

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]

A new ultra-fast and accurate method was developed to measure sulforaphane (SFN) and its precursor glucoraphanin (GR) in human urine, demonstrating over 87% recovery and low variability, which is crucial for studying their effects in humans.

After consuming broccoli sprouts, participants showed up to 40% bioavailability of SFN, indicating that dietary intake of broccoli can effectively deliver this beneficial compound to the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new ultra-rapid UHPLC/MS/MS method for assessing glucoraphanin and sulforaphane bioavailability in human urine. Dominguez-Perles, R., Medina, S., Moreno, DÁ., et al.[2021]

Sulforaphane (SFN), found in broccoli sprouts, significantly protects against aspirin/NSAIDs-induced small intestinal injury in both in vitro and in vivo studies, suggesting its potential as a preventive treatment.

The protective effects of SFN are linked to the up-regulation of the nrf2-keap1 dependent antioxidant system and a reduction in the invasion of harmful anaerobic bacteria into the intestinal mucosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulforaphane protects small intestinal mucosa from aspirin/NSAID-induced injury by enhancing host defense systems against oxidative stress and by inhibiting mucosal invasion of anaerobic enterobacteria. Yanaka, A., Sato, J., Ohmori, S.[2021]

Sulforaphane (SF), a beneficial compound from broccoli, is absorbed more effectively from myrosinase-rich broccoli sprouts compared to glucoraphanin-rich broccoli powder, with a 74% recovery in urine from sprouts versus only 19% from the powder.

Combining broccoli sprouts with the powder improved SF absorption, suggesting that this combination could enhance the health benefits of broccoli products without causing any toxicity, as indicated by liver function tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulforaphane absorption and excretion following ingestion of a semi-purified broccoli powder rich in glucoraphanin and broccoli sprouts in healthy men. Cramer, JM., Jeffery, EH.[2021]

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]

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]

Citations

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

Safety, Feasibility and Efficacy of Sulforaphane (Avmacol ... Study Overview​​ The Sulforaphane Production System® in Avmacol Extra Strength (ES) supplies broccoli seed extract (glucoraphanin) and Myrosimax® (Active ...

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

Broccoli or Sulforaphane: Is It the Source or Dose That ... A cross-over clinical trial with 50 human volunteers, which was conducted in Qidong, China, found statistically significant increases of 20–50% in the urinary ...

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

Safety, Feasibility and Efficacy of Sulforaphane (Avmacol ... We hypothesize that daily intake of sulforaphane (Avmacol Extra Strength (ES)) can decrease kidney disease progression rate and decrease markers of ...

4. 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9105060/

Randomized Crossover Trial Evaluating Detoxification of ... This randomized, crossover trial evaluated detoxification of tobacco carcinogens by two doses of the BSSE Avmacol ® in 49 otherwise healthy tobacco smokers.

6. webmd.com webmd.com/vitamins/ai/ingredientmono-1070/sulforaphane

Sulforaphane - Uses, Side Effects, and More It is possibly safe when used as medicine. Sulforaphane and sulforaphane-rich broccoli extract products have been used safely for up to 6 months. It's usually ...

7. amazon.com amazon.com/Sulforaphane-Producing-Detoxification-Antioxidant-Nutramax-Laboratories/dp/B08841KRMT

Nutramax Laboratories Avmacol Extra Strength #1 ... This item is non-returnable due to potential safety risk as an ingestible product, but if the item arrives damaged or defective, you may request a refund or ...

8. avmacol.com avmacol.com/products/avmacol-extra-strength

Buy Avmacol® Extra Strength Our exclusive Sulforaphane Production System® is validated in humans by measuring metabolites of sulforaphane collected in the urine.