Safety, Feasibility and Efficacy of Sulforaphane (Avmacol Extra Strength) in Chronic Kidney Disease - Randomized, Double-blind, Placebo-controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 96
- 试验地点
- 2
- 主要终点
- Longitudinal change in plasma hydrogen sulfide
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Placebo
Nutramax will provide the matched placebo tablets.
干预措施: Placebo (Dietary Supplement)
Sulforaphane (Avmacol Extra Strength)
Four tablets of Sulforaphane (Avmacol Extra Strength) per day. The tablets will be provided by Nutramax.
干预措施: Sulforaphane (Avmacol Extra Strength) (Drug)
结局指标
主要结局
Longitudinal change in plasma hydrogen sulfide
时间窗: Four timepoints per patient (baseline, month 1, month 3, and month 6)
Unit of measurement - Nanomolar (nM)
Longitudinal change in plasma interleukin-6
时间窗: Four timepoints per patient (baseline, month 1, month 3, and month 6)
Unit of measurement - picograms per milliliter (pg/mL)
Longitudinal change in urine nephrin
时间窗: 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)
时间窗: 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)
时间窗: Four timepoints per patient (baseline, month 1, month 3, and month 6)
Unit of measurement - Relative copy number
Longitudinal change in the scores
时间窗: Seven timepoints per patient (baseline; month 1; month 2; month 3; month 4; month 5, and month 6)
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.
Longitudinal change in both systolic and diastolic blood pressure
时间窗: Four timepoints per patient (baseline, month 1, month 3, and month 6)
Unit of measurement - millimeters of mercury (mmHg)
Longitudinal change in 8-isoprostane in plasma
时间窗: Four timepoints per patient (baseline, month 1, month 3, and month 6)
Unit of measurement - picograms per milliliter (pg/mL)
Longitudinal change in urinary albumin
时间窗: Four timepoints per patient (baseline, month 1, month 3, and month 6)
Unit of measurement - μg/ml
Longitudinal change in protein/creatinine ratio
时间窗: Four timepoints per patient (baseline, month 1, month 3, and month 6)
Unit of measurement - milligram per gram (mg/g)
Longitudinal change in 8-isoprostane in urine
时间窗: Four timepoints per patient (baseline, month 1, month 3, and month 6)
Unit of measurement - picograms per milliliter (pg/mL)
Longitudinal change in blood urea nitrogen as part of comprehensive metabolic panel (CMP)
时间窗: Four timepoints per patient (baseline, month 1, month 3, and month 6)
Unit of measurement - Milligrams per decilitre (mg/dL)
Longitudinal change in sodium as part of comprehensive metabolic panel (CMP)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: Four timepoints per patient (baseline, month 1, month 3, and month 6)
Unit of measurement - milliequivalents per liter (mEq/L)
Longitudinal change in creatinine as part of comprehensive metabolic panel (CMP)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: Four timepoints per patient (baseline, month 1, month 3, and month 6)
Unit of measurement - units per liter (U/L)
Longitudinal change in phosphorus as part of comprehensive metabolic panel (CMP)
时间窗: Four timepoints per patient (baseline, month 1, month 3, and month 6)
Unit of measurement - Milligrams per decilitre (mg/dL)
Longitudinal change in glucose as part of comprehensive metabolic panel (CMP)
时间窗: Four timepoints per patient (baseline, month 1, month 3, and month 6)
Unit of measurement - Milligrams per decilitre (mg/dL)
次要结局
未报告次要终点
研究者
Thu Le
John J. Kuiper Distinguished Professor of Medicine & Chief, Division of Nephrology
University of Rochester