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

Primary Purpose

Chronic Kidney Disease Stage 3, Chronic Kidney Disease Stage 4

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sulforaphane (Avmacol Extra Strength)
Placebo
Sponsored by
University of Rochester
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Kidney Disease Stage 3

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Rochester Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Sulforaphane (Avmacol Extra Strength)

Placebo

Arm Description

Four tablets of Sulforaphane (Avmacol Extra Strength) per day. The tablets will be provided by Nutramax.

Nutramax will provide the matched placebo tablets.

Outcomes

Primary Outcome Measures

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.
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.
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.
Longitudinal change in both systolic and diastolic blood pressure
Unit of measurement - millimeters of mercury (mmHg)
Longitudinal change in 8-isoprostane in plasma
Unit of measurement - picograms per milliliter (pg/mL)
Longitudinal change in 8-isoprostane in urine
Unit of measurement - picograms per milliliter (pg/mL)
Longitudinal change in urinary albumin
Unit of measurement - μg/ml
Longitudinal change in protein/creatinine ratio
Unit of measurement - milligram per gram (mg/g)
Longitudinal change in plasma hydrogen sulfide
Unit of measurement - Nanomolar (nM)
Longitudinal change in plasma interleukin-6
Unit of measurement - picograms per milliliter (pg/mL)
Longitudinal change in urine nephrin
Unit of measurement - microgram per milliliter μg/mL
Longitudinal change in messenger RNA (mRNA) levels of cytoprotective enzymes in peripheral blood mononuclear cells (PBMCs)
Unit of measurement - Relative copy number
Longitudinal change in messenger RNA (mRNA) levels of heat shock proteins in peripheral blood mononuclear cells (PBMCs)
Unit of measurement - Relative copy number
Longitudinal change in sodium as part of comprehensive metabolic panel (CMP)
Unit of measurement - Millimoles per liter (mmol/L)
Longitudinal change in potassium as part of comprehensive metabolic panel (CMP)
Unit of measurement - Millimoles per liter (mmol/L)
Longitudinal change in chloride as part of comprehensive metabolic panel (CMP)
Unit of measurement - Millimoles per liter (mmol/L)
Longitudinal change in carbon Dioxide as part of comprehensive metabolic panel (CMP)
Unit of measurement - Millimoles per liter (mmol/L)
Longitudinal change in anion Gap as part of comprehensive metabolic panel (CMP)
Unit of measurement - milliequivalents per liter (mEq/L)
Longitudinal change in blood urea nitrogen as part of comprehensive metabolic panel (CMP)
Unit of measurement - Milligrams per decilitre (mg/dL)
Longitudinal change in creatinine as part of comprehensive metabolic panel (CMP)
Unit of measurement - Milligrams per decilitre (mg/dL)
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)
Longitudinal change in calcium as part of comprehensive metabolic panel (CMP)
Unit of measurement - Milligrams per decilitre (mg/dL)
Longitudinal change in total protein as part of comprehensive metabolic panel (CMP)
Unit of measurement - Grams Per Deciliter (g/dL)
Longitudinal change in albumin as part of comprehensive metabolic panel (CMP)
Unit of measurement - Grams Per Deciliter (g/dL)
Longitudinal change in total bilirubin as part of comprehensive metabolic panel (CMP)
Unit of measurement - Milligrams per decilitre (mg/dL)
Longitudinal change in aspartate transaminase (AST) as part of comprehensive metabolic panel (CMP)
Unit of measurement - units per liter (U/L)
Longitudinal change in alanine transaminase (ALT) as part of comprehensive metabolic panel (CMP)
Unit of measurement - units per liter (U/L)
Longitudinal change in alkaline phosphatase (ALP) as part of comprehensive metabolic panel (CMP)
Unit of measurement - units per liter (U/L)
Longitudinal change in phosphorus as part of comprehensive metabolic panel (CMP)
Unit of measurement - Milligrams per decilitre (mg/dL)
Longitudinal change in glucose as part of comprehensive metabolic panel (CMP)
Unit of measurement - Milligrams per decilitre (mg/dL)

Secondary Outcome Measures

Full Information

First Posted
March 2, 2023
Last Updated
July 11, 2023
Sponsor
University of Rochester
Collaborators
University of Virginia, Nutramax Laboratories, Inc., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT05797506
Brief Title
Safety, Feasibility and Efficacy of Sulforaphane (Avmacol Extra Strength) in Chronic Kidney Disease
Official Title
Safety, Feasibility and Efficacy of Sulforaphane (Avmacol Extra Strength) in Chronic Kidney Disease - Randomized, Double-blind, Placebo-controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 3, 2023 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Rochester
Collaborators
University of Virginia, Nutramax Laboratories, Inc., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Disease Stage 3, Chronic Kidney Disease Stage 4

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sulforaphane (Avmacol Extra Strength)
Arm Type
Experimental
Arm Description
Four tablets of Sulforaphane (Avmacol Extra Strength) per day. The tablets will be provided by Nutramax.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Nutramax will provide the matched placebo tablets.
Intervention Type
Drug
Intervention Name(s)
Sulforaphane (Avmacol Extra Strength)
Intervention Description
4 Tablets of Sulforaphane (Avmacol Extra Strength) per day in patients with Chronic Kidney Disease, stages 3-4.
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
These tablets will be matched placebos and will be provided by Avmacol.
Primary Outcome Measure Information:
Title
Longitudinal change in the scores
Description
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.
Time Frame
Seven timepoints per patient (baseline; month 1; month 2; month 3; month 4; month 5, and month 6)
Title
Longitudinal change in the scores
Description
Modified Kansas City Cardiomyopathy questionnaire (KCCQ) - All KCCQ scores are scaled from 0 to 100. A higher score indicates better health status.
Time Frame
Seven timepoints per patient (baseline; month 1; month 2; month 3; month 4; month 5, and month 6)
Title
Longitudinal change in the scores
Description
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.
Time Frame
Seven timepoints per patient (baseline; month 1; month 2; month 3; month 4; month 5, and month 6)
Title
Longitudinal change in both systolic and diastolic blood pressure
Description
Unit of measurement - millimeters of mercury (mmHg)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in 8-isoprostane in plasma
Description
Unit of measurement - picograms per milliliter (pg/mL)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in 8-isoprostane in urine
Description
Unit of measurement - picograms per milliliter (pg/mL)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in urinary albumin
Description
Unit of measurement - μg/ml
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in protein/creatinine ratio
Description
Unit of measurement - milligram per gram (mg/g)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in plasma hydrogen sulfide
Description
Unit of measurement - Nanomolar (nM)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in plasma interleukin-6
Description
Unit of measurement - picograms per milliliter (pg/mL)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in urine nephrin
Description
Unit of measurement - microgram per milliliter μg/mL
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in messenger RNA (mRNA) levels of cytoprotective enzymes in peripheral blood mononuclear cells (PBMCs)
Description
Unit of measurement - Relative copy number
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in messenger RNA (mRNA) levels of heat shock proteins in peripheral blood mononuclear cells (PBMCs)
Description
Unit of measurement - Relative copy number
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in sodium as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - Millimoles per liter (mmol/L)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in potassium as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - Millimoles per liter (mmol/L)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in chloride as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - Millimoles per liter (mmol/L)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in carbon Dioxide as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - Millimoles per liter (mmol/L)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in anion Gap as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - milliequivalents per liter (mEq/L)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in blood urea nitrogen as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - Milligrams per decilitre (mg/dL)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in creatinine as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - Milligrams per decilitre (mg/dL)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in estimated Glomerular Filtration Rate (eGFR) as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - milliliters of cleansed blood per minute per body surface (mL/min/1.73m2)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in calcium as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - Milligrams per decilitre (mg/dL)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in total protein as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - Grams Per Deciliter (g/dL)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in albumin as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - Grams Per Deciliter (g/dL)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in total bilirubin as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - Milligrams per decilitre (mg/dL)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in aspartate transaminase (AST) as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - units per liter (U/L)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in alanine transaminase (ALT) as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - units per liter (U/L)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in alkaline phosphatase (ALP) as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - units per liter (U/L)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in phosphorus as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - Milligrams per decilitre (mg/dL)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)
Title
Longitudinal change in glucose as part of comprehensive metabolic panel (CMP)
Description
Unit of measurement - Milligrams per decilitre (mg/dL)
Time Frame
Four timepoints per patient (baseline, month 1, month 3, and month 6)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Thu Le, MD, FAHA
Phone
585-275-1554
Email
thu_le@urmc.rochester.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Sharvari Sonawane, MS
Email
sharvari_sonawane@urmc.rochester.edu
Facility Information:
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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

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