Study of Sulphoraphane in Chronic Kidney Disease

We hypothesize that daily intake of sulforaphane (Avmacol Extra Strength (ES)) can decrease kidney disease progression rate and decrease markers of oxidative stress and inflammation in chronic kidney disease (CKD) patients. To test our hypothesis, we will first perform a randomized, Phase 1 clinical trial in a single center funded by an R01 NIDDK award. This is an interventional pharmacokinetic trial, with subjects randomized to different doses of Avmacol ES.

• Sulforaphane (Drug), also known as Avmacol: This is an over-the counter nutritional supplement. Participants will be given the extra strength tablets.

Primary outcomes

• Area Under the Concentration-Time Curve (AUC 0-8h) in Plasma [prior to initial dose on day 7 and 1, 2, 4, and 8 hours post-dose]: Sulforaphane drug levels will be measured in plasma at 0, 1, 2, 4, and 8 hours.
• Area Under the Concentration-Time Curve (AUC 0-8h) in Urine [prior to initial dose on day 7 and 1, 2, 4, and 8 hours post-dose]: Sulforaphane drug levels will be measured in urine at 0, 1, 2, 4, and 8 hours.
• Number of Participants With an Adverse Event [day 7]: Adverse Event is any side effect outside of the subject's baseline.

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

* eGFR ≥ 20 and <60 ml/min/m2/year, and a decline in eGFR of ≥ 3 ml/min/m2/year in the previous 12 months
* Blood pressure <140/90 mm Hg prior to initiation of sulphoraphane
* stable anti-hypertensive regimen for at least one month prior to initiation of sulphoraphane or successful run-in period
* able to provide consent
* able to swallow capsules

Exclusion Criteria:

* significant co-morbid conditions with life expectancy of <1 year
* uncontrolled hypertension
* serum potassium of >5.5 mEq/L at screening
* 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
* factors judged to limit adherence to interventions
* current participation in another study
* pregnancy or planning to become pregnant or currently breastfeeding
* history of dementia
* on anticoagulants or immunosuppression
* under treatment for cancer

Participant flow

Outcome results

• Area Under the Concentration-Time Curve (AUC 0-8h) in Plasma (Primary), Mean, nmol h/L: 2 Tablets of Sulforaphane 700.0 +/- 376.5; 4 Tablets of Sulforaphane 718.4 +/- 335.8 (p 0.931)
• Area Under the Concentration-Time Curve (AUC 0-8h) in Urine (Primary), Mean, nmol h/L: 2 Tablets of Sulforaphane 12497.0 +/- 9569.2; 4 Tablets of Sulforaphane 24928.8 +/- 23028.8 (p 0.224)
• Number of Participants With an Adverse Event (Primary), Count of participants, Participants: 2 Tablets of Sulforaphane 5; 4 Tablets of Sulforaphane 7

Adverse events

Time frame: 10 months, 11 days

Other adverse events by term

Limitations and caveats: At the time of review with the Data Safety Monitoring Committee, the study had consented 21 patients and enrolled 18 patients out of 24 targeted. 2 of the 21 patients were randomized to a 6-tablet Arm, which was removed in the final Protocol Amendment due to moderate side effects/adverse events. 1 patient withdrew before study procedures.

• Study Protocol and Statistical Analysis Plan (PDF, 2022-11-17)
• Informed Consent Form (PDF, 2022-12-09)

• Thu H Le, MD, FAHA, Principal investigator, Division of Nephrology Chief

NIH grants: R01DK128677