Study of Sulphoraphane in Chronic Kidney Disease

Phase 1

Completed

Brief Summary: The purpose of this study is to test the safety of the compound sulforaphane that boosts the activity of antioxidant genes in the body to combat oxidative stress. Oxidative stress has been shown experimentally to play a role in kidney disease. This drug has been tested in patients with breast cancer who have normal kidney function, but has never been tested in patients with kidney disease.

In this study, the investigators will establish a safe dose for patients with chronic kidney disease based on blood levels achieved in patients with normal kidney function.

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
2 tablets of Sulforaphane	Sulforaphane	Participants will be given 2 extra strength tablets per day
4 tablets of Sulforaphane	Sulforaphane	Participants will be given 4 extra strength tablets per day

Primary Outcome Measures

Name	Time	Method
Number of Participants With an Adverse Event	day 7	Adverse Event is any side effect outside of the subject's baseline.
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.