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

Chronic Kidney Disease Stage 3 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05797506
• Other study ID #: STUDY00008014
• Secondary ID: R01DK128677
• Status: Recruiting
• Phase: Phase 2
• Start date: May 3, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2024
• Source: University of Rochester
• Contact: Thu Le, MD, FAHA
• Phone: 585-275-1554
• Email: thu_le[@]urmc.rochester.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Kidney Disease Stage 3
• Chronic Kidney Disease Stage 4
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Sulforaphane (Avmacol Extra Strength)
4 Tablets of Sulforaphane (Avmacol Extra Strength) per day in patients with Chronic Kidney Disease, stages 3-4.

Dietary Supplement:
• Placebo
These tablets will be matched placebos and will be provided by Avmacol.

Locations

Country	Name	City	State
United States	University of Rochester Medical Center	Rochester	New York

Sponsors (4)

Lead Sponsor	Collaborator
University of Rochester	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Nutramax Laboratories, Inc., University of Virginia

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	Longitudinal change in urinary albumin	Unit of measurement - µg/ml	Four timepoints per patient (baseline, month 1, month 3, and month 6)
Primary	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)
Primary	Longitudinal change in plasma hydrogen sulfide	Unit of measurement - Nanomolar (nM)	Four timepoints per patient (baseline, month 1, month 3, and month 6)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)