Safety, Feasibility and Efficacy of Sulforaphane (Avmacol Extra Strength) in Chronic Kidney Disease

Study Overview
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Brief Summary
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The Sulforaphane Production System® in Avmacol Extra Strength (ES) supplies broccoli seed extract (glucoraphanin) and Myrosimax® (Active Myrosinase Enzyme) which helps promote sulforaphane production in your body. The investigators hypothesize that daily intake of Avmacol ES can decrease kidney disease progression rate and decrease markers of oxidative stress and inflammation in Chronic Kidney Disease (CKD) patients. They will test this hypothesis in a randomized, double-blind, placebo controlled Phase 2 clinical trial. This proposed study has been funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), R01 DK128677.

Detailed Description
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The investigators will test the safety and efficacy of Avmacol ES in Chronic Kidney Disease (CKD) patients. After having established a safe dose of 4 tablets once daily in participants with CKD Stages 3 - 4 in the pharmacokinetic (PK) phase, the investigators will enroll 100 participants from the Kidney Clinic at the University of Rochester Medical Center and Highland Hospital with CKD stages 3 - 4 who will be randomized to Avmacol ES or placebo in a 1:1 ratio in a blinded manner.

Official Title
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Safety, Feasibility and Efficacy of Sulforaphane (Avmacol Extra Strength) in Chronic Kidney Disease - Randomized, Double-blind, Placebo-controlled Trial

Conditions
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Chronic Kidney Disease Stage 3, Chronic Kidney Disease Stage 4

Intervention / Treatment
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* Drug: Sulforaphane (Avmacol Extra Strength)
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years and ≤ 80 years Estimated glomerular filtration rate (eGFR) ≥ 20 and < 60 mL/min/1.73m2 and a decline in eGFR of ≥ 3 ml/min/1.73m2 /year in the previous 12 ± 2 months Able to provide consent Able to swallow Avmacol ES or placebo capsules Exclusion Criteria: Significant co-morbid conditions with life expectancy of < 1 year Serum potassium of > 5.5 milliequivalents per liter (mEq/L) at screening New York Heart Association Class 3 or 4 heart failure symptoms, known Ejection Fraction (EF) ≤ 30% or hospital admission for heart failure within the past 3 months Factors judged to limit adherence to interventions based on appointment attendance and medication treatment compliance; PI will make this determination Current participation in another medical intervention study Known to be pregnant or planning to become pregnant or currently breastfeeding; determined by self-report and medical record history. A urine pregnancy test will be completed for individuals of childbearing potential before administering the study drug, and repeated thereafter at every study visit (  every 3-4 months) History of dementia documented in the medical record On anticoagulants or immunosuppression Under treatment for cancer Delayed gastric emptying or similar GI conditions Non-English-speaking individuals are excluded in this randomized phase of the study because the lack of English proficiency will affect a subject's ability to report problems or adverse events. If a patient cannot read, the consent form will be read to them by the research coordinator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sulforaphane (Avmacol Extra Strength)<br>Four tablets of Sulforaphane (Avmacol Extra Strength) per day. The tablets will be provided by Nutramax. | Drug: Sulforaphane (Avmacol Extra Strength)<br>* 4 Tablets of Sulforaphane (Avmacol Extra Strength) per day in patients with Chronic Kidney Disease, stages 3-4.<br>|
| Placebo Comparator: Placebo<br>Nutramax will provide the matched placebo tablets. | Dietary Supplement: Placebo<br>* These tablets will be matched placebos and will be provided by Avmacol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Longitudinal change in the scores | Patient-Reported Outcomes Measurement Information System (PROMIS®) Scale v1.2 - Global Health questionnaire. Scoring: The questionnaire has two scores: Physical Health (physical health, physical function, pain, and fatigue items) and Mental Health (quality of life, mental health, satisfaction with discretionary social activities, and emotional problem items). In all cases, a high score means more of domain. T scores for both Physical and Mental Health scales. In all cases, a high score means more of domain. For example, higher scores on physical functioning measure indicate better health. | Seven timepoints per patient (baseline; month 1; month 2; month 3; month 4; month 5, and month 6) | 
| Longitudinal change in the scores | Modified Kansas City Cardiomyopathy questionnaire (KCCQ) - All KCCQ scores are scaled from 0 to 100. A higher score indicates better health status. | Seven timepoints per patient (baseline; month 1; month 2; month 3; month 4; month 5, and month 6) | 
| Longitudinal change in the scores | Patient-Reported Outcomes Measurement Information System (PROMIS®) Scale v1.0 - Gastrointestinal Belly Pain 5a questionnaire. The PROMIS GI measures use a T-score centered on the U.S. General Population. This means that a score of 50 represents the average of the general population (and that 10 represents the standard deviation). A higher PROMIS T-score represents more of the concept being measured. For negatively-worded concepts like belly pain, a T-score of 60 is one SD worse than average. By comparison, a gastrointestinal symptom T-score of 40 is one SD better than average. | Seven timepoints per patient (baseline; month 1; month 2; month 3; month 4; month 5, and month 6) | 
| Longitudinal change in both systolic and diastolic blood pressure | Unit of measurement - millimeters of mercury (mmHg) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in 8-isoprostane in plasma | Unit of measurement - picograms per milliliter (pg/mL) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in 8-isoprostane in urine | Unit of measurement - picograms per milliliter (pg/mL) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in urinary albumin | Unit of measurement - μg/ml | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in protein/creatinine ratio | Unit of measurement - milligram per gram (mg/g) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in plasma hydrogen sulfide | Unit of measurement - Nanomolar (nM) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in plasma interleukin-6 | Unit of measurement - picograms per milliliter (pg/mL) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in urine nephrin | Unit of measurement - microgram per milliliter μg/mL | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in messenger RNA (mRNA) levels of cytoprotective enzymes in peripheral blood mononuclear cells (PBMCs) | Unit of measurement - Relative copy number | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in messenger RNA (mRNA) levels of heat shock proteins in peripheral blood mononuclear cells (PBMCs) | Unit of measurement - Relative copy number | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in sodium as part of comprehensive metabolic panel (CMP) | Unit of measurement - Millimoles per liter (mmol/L) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in potassium as part of comprehensive metabolic panel (CMP) | Unit of measurement - Millimoles per liter (mmol/L) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in chloride as part of comprehensive metabolic panel (CMP) | Unit of measurement - Millimoles per liter (mmol/L) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in carbon Dioxide as part of comprehensive metabolic panel (CMP) | Unit of measurement - Millimoles per liter (mmol/L) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in anion Gap as part of comprehensive metabolic panel (CMP) | Unit of measurement - milliequivalents per liter (mEq/L) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in blood urea nitrogen as part of comprehensive metabolic panel (CMP) | Unit of measurement - Milligrams per decilitre (mg/dL) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in creatinine as part of comprehensive metabolic panel (CMP) | Unit of measurement - Milligrams per decilitre (mg/dL) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in estimated Glomerular Filtration Rate (eGFR) as part of comprehensive metabolic panel (CMP) | Unit of measurement - milliliters of cleansed blood per minute per body surface (mL/min/1.73m2) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in calcium as part of comprehensive metabolic panel (CMP) | Unit of measurement - Milligrams per decilitre (mg/dL) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in total protein as part of comprehensive metabolic panel (CMP) | Unit of measurement - Grams Per Deciliter (g/dL) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in albumin as part of comprehensive metabolic panel (CMP) | Unit of measurement - Grams Per Deciliter (g/dL) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in total bilirubin as part of comprehensive metabolic panel (CMP) | Unit of measurement - Milligrams per decilitre (mg/dL) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in aspartate transaminase (AST) as part of comprehensive metabolic panel (CMP) | Unit of measurement - units per liter (U/L) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in alanine transaminase (ALT) as part of comprehensive metabolic panel (CMP) | Unit of measurement - units per liter (U/L) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in alkaline phosphatase (ALP) as part of comprehensive metabolic panel (CMP) | Unit of measurement - units per liter (U/L) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in phosphorus as part of comprehensive metabolic panel (CMP) | Unit of measurement - Milligrams per decilitre (mg/dL) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | 
| Longitudinal change in glucose as part of comprehensive metabolic panel (CMP) | Unit of measurement - Milligrams per decilitre (mg/dL) | Four timepoints per patient (baseline, month 1, month 3, and month 6) |