Chronic Kidney Disease stage3, Chronic Kidney Disease stage4
Conditions
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.
Interventions
DRUGSulforaphane
This is an over-the counter nutritional supplement. Participants will be given the extra strength tablets.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Pre-assignment details
1 patient was withdrawn for screen failure before randomizing to an Arm. eGFR (Estimated Glomerular Filtration Rate) lab value was stable & out of eligibility range. 2 patients were randomized to a 6-tablet Arm which was removed in the final Protocol Amendment due to moderate side effects.
Participants by arm
| Arm | Count |
|---|---|
| 2 Tablets of Sulforaphane Participants will be given 2 extra strength tablets per day
Sulforaphane: This is an over-the counter nutritional supplement. Participants will be given the extra strength tablets. | 9 |
| 4 Tablets of Sulforaphane Participants will be given 4 extra strength tablets per day
Sulforaphane: This is an over-the counter nutritional supplement. Participants will be given the extra strength tablets. | 9 |
| Total | 18 |
Baseline characteristics
| Characteristic | 2 Tablets of Sulforaphane | 4 Tablets of Sulforaphane | Total |
|---|---|---|---|
| Age, Continuous | 66 years STANDARD_DEVIATION 10.3327359445 | 64 years STANDARD_DEVIATION 11.1698447661 | 64.4 years STANDARD_DEVIATION 10.256793556417 |
| Estimated Glomerular Filtration Rate (eGFR) level at Baseline | 33.3 mL/min/1.73 m2 | 34.6 mL/min/1.73 m2 | 34.2 mL/min/1.73 m2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 9 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Glutathione S-Transferase Mu 1 (GSTM1) Genotype GSTM1 (0/0) Null | 5 Participants | 5 Participants | 10 Participants |
| Glutathione S-Transferase Mu 1 (GSTM1) Genotype GSTM1 (1/1 or 1/0) Allele | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 8 Participants | 14 Participants |
| Region of Enrollment United States | 9 participants | 9 participants | 18 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
| Stage of Chronic Kidney Disease (CKD) Stage 3 CKD (eGFR 30-59) | 8 Participants | 7 Participants | 15 Participants |
| Stage of Chronic Kidney Disease (CKD) Stage 4 CKD (eGFR 15-29) | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 4 / 9 | 7 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 |
Outcome results
Primary
Area Under the Concentration-Time Curve (AUC 0-8h) in Plasma
Sulforaphane drug levels will be measured in plasma at 0, 1, 2, 4, and 8 hours.
Time frame: prior to initial dose on day 7 and 1, 2, 4, and 8 hours post-dose
Population: First 6 samples (2 from each arm) not included due to problem with standards resulting in no absolute quantification.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 Tablets of Sulforaphane | Area Under the Concentration-Time Curve (AUC 0-8h) in Plasma | 700.0 nmol h/L | Standard Deviation 376.5 |
| 4 Tablets of Sulforaphane | Area Under the Concentration-Time Curve (AUC 0-8h) in Plasma | 718.4 nmol h/L | Standard Deviation 335.8 |
p-value: 0.931t-test, 2 sided
Primary
Area Under the Concentration-Time Curve (AUC 0-8h) in Urine
Sulforaphane drug levels will be measured in urine at 0, 1, 2, 4, and 8 hours.
Time frame: prior to initial dose on day 7 and 1, 2, 4, and 8 hours post-dose
Population: First 6 samples (2 from each arm) not included due to problem with standards resulting in no absolute quantification.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 Tablets of Sulforaphane | Area Under the Concentration-Time Curve (AUC 0-8h) in Urine | 12497.0 nmol h/L | Standard Deviation 9569.2 |
| 4 Tablets of Sulforaphane | Area Under the Concentration-Time Curve (AUC 0-8h) in Urine | 24928.8 nmol h/L | Standard Deviation 23028.8 |
p-value: 0.224t-test, 2 sided
Primary
Number of Participants With an Adverse Event
Adverse Event is any side effect outside of the subject's baseline.
Time frame: day 7
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 2 Tablets of Sulforaphane | Number of Participants With an Adverse Event | 5 Participants |
| 4 Tablets of Sulforaphane | Number of Participants With an Adverse Event | 7 Participants |