Study of Sulphoraphane in 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

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing sulforaphane, a compound that helps protect cells from damage, in patients with chronic kidney disease. The goal is to find a safe dose for these patients. Sulforaphane works by boosting the body's natural defenses against harmful molecules. It has been studied for its protective effects against various types of kidney damage, including those caused by certain medications and toxins.

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.

What data supports the effectiveness of the treatment involving Sulforaphane, Avmacol ES, Avmacol Extra Strength, Broccoli seed extract, and Glucoraphanin?

Research shows that sulforaphane, a compound derived from broccoli, has potential health benefits, including cancer prevention, by activating certain protective enzymes in the body. Studies indicate that consuming broccoli or its extracts can increase the availability of sulforaphane in the body, which may help in disease prevention. ^{1 2 3 4 5}

Is sulforaphane safe for human consumption?

Research shows that sulforaphane, found in broccoli sprouts, is generally safe for humans. Clinical studies have not reported significant safety concerns or toxic effects from consuming sulforaphane or its precursor, glucoraphanin, in healthy volunteers. ^{1 2 6 7 8}

How is the treatment Sulforaphane unique compared to other treatments?

Sulforaphane, derived from broccoli, is unique because it is a natural compound that can be absorbed more effectively when combined with myrosinase-rich foods, enhancing its bioavailability. This treatment is notable for its potential chemopreventive properties, which may help in preventing certain diseases by activating protective pathways in the body. ^{2 5 8 9 10}

Research Team

Thu H Le, MD, FAHA

Principal Investigator

Division of Nephrology Chief

Eligibility Criteria

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

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

Treatment Details

Interventions

• Sulforaphane

Participant Groups

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+

Findings from Research

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]

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 (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]

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 (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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

Sulforaphane Bioavailability from Glucoraphanin-Rich Broccoli: Control by Active Endogenous Myrosinase. [2022]

4. 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]

5. United States 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. [2021]

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. United Arab Emirates 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. [2021]

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

Anti-obesity effect of sulforaphane in broccoli leaf extract on 3T3-L1 adipocytes and ob/ob mice. [2022]

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

A new ultra-rapid UHPLC/MS/MS method for assessing glucoraphanin and sulforaphane bioavailability in human urine. [2021]

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

Separation and purification of sulforaphane from broccoli seeds by solid phase extraction and preparative high-performance liquid chromatography. [2021]