Chronic Kidney Disease Stage 3, Chronic Kidney Disease Stage 4
Conditions
Brief summary
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
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.
Interventions
DRUGSulforaphane (Avmacol Extra Strength)
4 Tablets of Sulforaphane (Avmacol Extra Strength) per day in patients with Chronic Kidney Disease, stages 3-4.
DIETARY_SUPPLEMENTPlacebo
These tablets will be matched placebos and will be provided by Avmacol.
Sponsors
University of Rochester
University of Virginia
Nutramax Laboratories, Inc.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Plasma 8 Isoprostane From Baseline | Baseline, Month 1, Month 3, and Month 6 | Plasma 8 isoprostane in picograms per milliliter was measured at baseline and at Months 1, 3, and 6. For each participant at each follow up visit, change from baseline was calculated as follow up value minus baseline value. Mean change and standard deviation are reported separately at Month 1, Month 3, and Month 6. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Longitudinal Change in Urinary Albumin | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - μg/ml |
| Longitudinal Change in Protein/Creatinine Ratio | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - milligram per gram (mg/g) |
| Longitudinal Change in Urine Nephrin | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - microgram per milliliter μg/mL |
| Longitudinal Change in Messenger RNA (mRNA) Levels of Cytoprotective Enzymes in Peripheral Blood Mononuclear Cells (PBMCs) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - Relative copy number |
| Longitudinal Change in Messenger RNA (mRNA) Levels of Heat Shock Proteins in Peripheral Blood Mononuclear Cells (PBMCs) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - Relative copy number |
| Longitudinal Change in Sodium as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - Millimoles per liter (mmol/L) |
| Longitudinal Change in Potassium as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - Millimoles per liter (mmol/L) |
| Longitudinal Change in Chloride as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - Millimoles per liter (mmol/L) |
| Longitudinal Change in Carbon Dioxide as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - Millimoles per liter (mmol/L) |
| Longitudinal Change in Anion Gap as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - milliequivalents per liter (mEq/L) |
| Longitudinal Change in Blood Urea Nitrogen as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - Milligrams per decilitre (mg/dL) |
| Longitudinal Change in Creatinine as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - Milligrams per decilitre (mg/dL) |
| Longitudinal Change in Estimated Glomerular Filtration Rate (eGFR) as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - milliliters of cleansed blood per minute per body surface (mL/min/1.73m2) |
| Longitudinal Change in Calcium as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - Milligrams per decilitre (mg/dL) |
| Longitudinal Change in Total Protein as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - Grams Per Deciliter (g/dL) |
| Longitudinal Change in Albumin as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - Grams Per Deciliter (g/dL) |
| Longitudinal Change in Total Bilirubin as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - Milligrams per decilitre (mg/dL) |
| Longitudinal Change in Aspartate Transaminase (AST) as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - units per liter (U/L) |
| Longitudinal Change in Alanine Transaminase (ALT) as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - units per liter (U/L) |
| Longitudinal Change in Alkaline Phosphatase (ALP) as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - units per liter (U/L) |
| Longitudinal Change in Glucose as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - Milligrams per decilitre (mg/dL) |
| Longitudinal Change in Phosphorus as Part of Comprehensive Metabolic Panel (CMP) | Four timepoints per patient (baseline, month 1, month 3, and month 6) | Unit of measurement - Milligrams per decilitre (mg/dL) |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 35 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 94 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| GSTM1 Genotype Genotype (0/0) | 53 Participants |
| GSTM1 Genotype Genotype (1/1) or (1/0) | 24 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Sex/Gender, Customized Female | 18 Participants |
| Sex/Gender, Customized Male | 26 Participants |
| Sex/Gender, Customized Transgender Female | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 47 |
| other Total, other adverse events | 39 / 49 | 34 / 47 |
| serious Total, serious adverse events | 1 / 49 | 0 / 47 |
Outcome results
None listed