Clinical trial NCT05153174
Conditions: Chronic Kidney Disease stage3 Chronic Kidney Disease stage4
Sponsor: University of Rochester
Start date: 2022-05-02; Completion date: 2023-06-08
Enrollment: 18 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to test the safety of the compound sulforaphane that boosts the activity of antioxidant genes in the body to combat oxidative stress. Oxidative stress has been shown experimentally to play a role in kidney disease. This drug has been tested in patients with breast cancer who have normal kidney function, but has never been tested in patients with kidney disease.

In this study, the investigators will establish a safe dose for patients with chronic kidney disease based on blood levels achieved in patients with normal kidney function.

Detailed description:
We hypothesize that daily intake of sulforaphane (Avmacol Extra Strength (ES)) can decrease kidney disease progression rate and decrease markers of oxidative stress and inflammation in chronic kidney disease (CKD) patients. To test our hypothesis, we will first perform a randomized, Phase 1 clinical trial in a single center funded by an R01 NIDDK award. This is an interventional pharmacokinetic trial, with subjects randomized to different doses of Avmacol ES.

Arms: arm 1: Participants will be given 2 extra strength tablets per day arm 2: Participants will be given 4 extra strength tablets per day
Interventions: intervention 1: Sulforaphane
Intervention descriptions: intervention 1: This is an over-the counter nutritional supplement. Participants will be given the extra strength tablets.

Protocol documents:
Prot_SAP_000.pdf: 
Safety, Feasibility and Efficacy of Sulforaphane
(Avmacol Extra Strength) in Chronic Kidney Disease – Phase I
Principal Investigator – Thu H. Le, MD
1. PURPOSE OF STUDY
We hypothesize that daily intake of sulforaphane (Avmacol Extra Strength (ES)) can decrease kidney
disease progression rate and decrease markers of oxidative stress and inflammation in chronic kidney
disease (CKD) patients. We will test our hypothesis in a randomized, double-blind, placebo-controlled
Phase 1/2 clinical trial in a single center, two sites, 3-year study. This proposed study was submitted as an
R01 application in response to FOA PAS-20-160 that encourages submission of pilot and feasibility
clinical trials that will lay the foundation for larger clinical trials related to the prevention/treatment of
CKD within the mission of NIDDK. We have received a Notice of Award for this study from
NIH/NIDDK.
There are two phases to our study; each will have a separate Consent Form. This proposal is only for
Phase I study. Once Phase I is complete, a new study will be submitted for Phase II. Please see study
design below for details:
1. Phase I: Establish pharmacokinetics of Avmacol ES in patients with CKD Stages 3-4
(first 6 months of the study). Subjects who participate in the first phase of the study may be
eligible to participate in the second phase of the study.
We seek approval for the Phase I of the study which will establish the dosing for the second phase
of the study.
2. BACKGROUND AND RATIONALE
In the United States (U.S.), the prevalence of chronic kidney disease (CKD) in adults is ~14%. The
mainstay of therapy for CKD are angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin
receptor blockers (ARBs), but many CKD patients still progress to end stage kidney disease (ESKD) – the
ultimate in failed prevention. The prevalence of ESKD is ~ 700,000, and is projected to increase to
between 971,000 – 1,259,000 patients by 2030 1.
Increased oxidative stress is a major molecular underpinning of CKD progression. In humans, a
common deletion variant of the glutathione-S-transferase μ-1 (GSTM1) gene, the GSTM1 null allele
(GSTM1(0)), results in decreased GSTM1 enzymatic activity and is associated with higher levels of
oxidative stress. GSTM1 belongs to the superfamily of GSTs that are phase II antioxidant enzymes and
are regulated by nuclear factor erythroid 2-related factor 2 (Nrf2). Our laboratory made the discovery that
the highly prevalent GSTM1(0) is associated with more rapid CKD progression in the African American
Study of Kidney Disease (AASK) trial participants 2. This association has been replicated in the
Atherosclerosis Risk in Communities (ARIC) study 3. In experimental mouse models of CKD or
hypertension, we found Gstm1 knockout (KO) mice have increased renal oxidative stress, inflammation,
and kidney injury, compared to wild-type (WT) littermate controls 4.
Cruciferous vegetables in general, and broccoli in particular, are rich in glucoraphanin, a precursor of
sulforaphane (SFN) that has been shown to have protective effects against oxidative damage through
activation of Nrf2. We found that dietary supplementation of sulforaphane-rich broccoli powder
ameliorated kidney disease only in Gstm1 KO mice. Similarly, in the ARIC study of nearly 11,000
patients, high intake of cruciferous vegetables was associated with lower risks of kidney failure, with
stronger effects in those homozygous for the null allele (GSTM1(0/0)). Our recently published paper
reporting these findings 4 was selected for news release based on “its overall excellence in furthering the
field of nephrology”, and was highlighted in several news outlets, including Science Daily and Reuters
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Health.
SFN is currently in clinical trials for cancer of the breast, lung, and prostate, as well as autism and
schizophrenia, and cardiotoxicity from chemotherapy (Clinicaltrials.gov). However, very few studies
have assessed the effect of SFN in kidney disease in pre-clinical experimental models; and, to the best of
our knowledge, no clinical study has been performed to assess the effect of SFN in CKD. Our
overarching objective is to test the safety, feasibility and efficacy of SFN in delaying CKD progression,
and, if so, whether its effect is dependent on GSTM1 genotype.
Once Phase I is completed and an appropriate dose is established, we will move to our Phase II pilot
study in which patients will be randomized to the study drug Avmacol ES and placebo for 6 months. We
hope that at the conclusion of the 3-year study, SFN will be demonstrated to be safe and well tolerated,
with measurable pharmacodynamic actions. The results would provide a sound rationale for Phase III and
a future large multicenter clinical trial to randomize CKD patients to standard care ± SFN to determine its
efficacy in slowing the rate of decline of eGFR in patients with CKD Stages 3-4 and its interaction with
GSTM1 genotype. Positive results in our study will also reinforce and establish further mechanistic
evidence for future research on the effects of regulation of the Nrf2-GSTM1 pathway on kidney function.
3. ADMINISTRATIVE ORGANIZATION
This is a multi-site collaborative study funded by the National Institutes of Health (NIH). The Nephrology
Division at Strong Memorial Hospital (SMH) will conduct the study to enroll patients. Subjects will be
recruited from the Kidney Clinic in AC-3, located at SMH, and from Highland Hospital. University of
Virginia will serve as a data analysis site (see Section #17). URMC will securely transfer de-identified
data to UVA for analysis.
4. STUDY DESIGN
Phase 1 study that will be conducted to establish pharmacokinetics of Avmacol ES in patients with
CKD Stages 3-4 and includes the following end-points:
Aim: To determine the pharmacokinetics of Avmacol ES in patients with CKD Stages 3-4
and the influence of GSTM1 genotype on bioavailability. Nutramax has expressed willingness to
provide Avmacol ES, a commercially available glucoraphanin packaged with the active enzyme
myrosinase to convert glucoraphanin to SFN. Regular Strength Avmacol has been tested in 16 clinical
trials, https://clinicaltrials.gov/ct2/results?cond=&term=Avmacol&cntry=&state=&city=&dist=, 9 of
which are still active. We will first establish an optimal dose for CKD Stages 3 and 4 patients to achieve
similar pharmacokinetic (PK) profile observed in non-CKD patients. We will also test our hypothesis
that there is higher bioavailability of SFN in CKD 3-4 patients carrying the GSTM1(0/0) genotype
compared to those carrying the active GSTM1 allele.
4.1 STUDY INTERVENTIONS
STUDY DRUG: Avmacol Extra Strength capsules
IND # 158689
IND HOLDER: Thu H. Le, MD
For Phase I, we will only use Avmacol ES, no placebo, to determine the PK of Avmacol ES in CKD to
guide the dose used for Phase II.
Nutramax Laboratories, Consumar Care, Inc., will provide Avmacol ES capsules free of charge in
bottles shipped directly to University of Rochester Medical Center (URMC) Clinical Research
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Once a Day
GSTM1 Genotype
Caucasians     African Americans
GSTM1 (1/1 or 1/0)
50%
73%
GSTM1 (0/0)
50%
27%
Pharmacy Investigational Drug Services (IDS). The IDS will store, monitor, and dispense the drug
directly to subjects. Data from the study will be shared with Nutramax.
It should be noted that, compared to control, SFN at “low dose” or 0.5 µM concentration, ex vivo, is able
to induce expression of the genes in human peripheral blood mononuclear cells (PBMCs) that encode the
enzymes AKR1C1 and NQO1 that play a role in reducing radical species 5. Higher doses of 2 µM and 5
µM of SFN induce higher expression of AKR1C1 and NQO1, as well as HO-1. Other human trials with
SFN have reported higher peak plasma concentrations of 1-2 µM 6.
GSTM1 genotype will first be determined for the PK analysis to assess whether the genotype influences
drug metabolism. Stratified by GSTM1 group, patients will
be assigned randomly to 2 or 4 Avmacol Extra Strength
Table 1: Number of Avmacol Extra Strength Tablets
tablets once a day, taken orally with food, as depicted in
GSTM1 Genotype
2 Tablets
4 Tablets
Table 1.
The groups are categorized into GSTM1 null
GSTM1 (1/1 or 1/0)                 6                         6
(GSTM1 (0/0) or GSTM1 non-null (GSTM1 (1/1) or
GSTM1 (0/0)                            6                         6
(1/0)) genotype based on the dominant model we observed in AASK and ARIC cohorts 2,3.
Between 800-900 patients are seen monthly in the 
Table 2
Prevalence
URMC Kidney Clinic in AC-3 and Highland Hospital.
Among these patients, ~ 60% have CKD Stage 3 or 4,
and ~ 40% of the total patients are African American.
The null genotype is quite common in human populations, with 50% Caucasians and 27% African
Americans being homozygous for the GSTM1 (0/0) allele (see Table 2 for prevalence of GSTM1
genotypes) 7. We saw similar prevalence of genotypes in AASK and ARIC 2-4. Therefore, we do not
anticipate difficulty identifying those with null versus non-null genotypes.
Rather than using a dose escalation approach which would take more time, we will be assessing 2
different doses simultaneously in different participants in each group to assess for the degree of variation
in PK. We will choose the highest dose that achieves similar t1/2 concentration and AUC0-8 of SFN levels
as observed in non-CKD patients (1-2 µM) 5,6 for our safety and efficacy study in Phase II.
Toxicities and guidelines for adjustments, withdrawals, etc.
In case of any significant side effects, adverse events or unusual changes, dosage will first be halved, and
if patient’s signs/symptoms do not improve after 3 days, treatment will be stopped. If signs/symptoms are
resolved, the treatment will be resumed at the lower dose for 7 days. On Day 7 when the patient comes in
for PK study. Otherwise, the study treatment will be stopped. If symptoms recur after resuming the lower
dose, Avmacol ES will be discontinued.
Reporting of Side Effects. Participants will be given instructions and contact information to report any
side effects, new symptoms or worsening of preexisting symptoms to the research coordinator or their
primary nephrologist (who will be made aware of the patient’s participation) during work hours. After
work hours, including nights and weekends, they will contact Dr. Le who is available 24 hours a day. If
Dr. Le is away, the Nephrology physician on call will take the calls for Dr. Le, so that 24/7 medical
coverage will be available for study participants. Any serious unexpected adverse effects will be
immediately reported to the IRB, the DSMB, and the NIH Office of Biotechnology Activities.
4.2 SUBJECT POPULATION
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We will enroll 24 adult patients followed in the Kidney Clinic in AC-3 with chronic kidney disease.
Evaluable subjects who withdraw from the study will be replaced to meet the enrollment goal. We will
recruit patients of any gender, race, and socioeconomic status.
Vulnerable Subjects: We do not plan to include vulnerable subjects such as children, pregnant women,
fetuses, or prisoners. Employees (physicians/fellows) will be assured that taking part in research is not a
part of their duties, and refusing to participate in the study will not affect their job. To ensure their
autonomy, the research coordinator (rather than the PI) will consent them.
5. INCLUSION AND EXCLUSION CRITERIA
Inclusion Criteria:
•
Age ≥ 18 years and ≤ 80 years
•
Estimated glomerular filtration rate (eGFR) ≥ 25 and < 45 mL/min/1.73m2
•
Able to provide consent
•
Able to swallow Avmacol ES capsules
Exclusion Criteria:
•
Significant co-morbid conditions with life expectancy of < 1 year
•
Uncontrolled hypertension; an average recorded blood pressure ≥140/90 mmHg in the past 6
months
•
Serum potassium of > 5.5 mEq/L at screening
•
New York Heart Association Class 3 or 4 heart failure symptoms, known 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 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.
•
History of dementia documented in the medical record
•
On anticoagulants or immunosuppression
•
Under treatment for cancer
Non-English-speaking individuals will be not be included in Phase I of the study, but will be included in
Phase II. If a patient cannot read, the consent form will be read to them by the research coordinator.
6. RECRUITMENT METHODS
Once eligible patients are identified, our research coordinator will reach out to each provider to ask them
if we may speak with their patients for the study.
Phone/Video Call: The research coordinator will contact eligible patients by phone to introduce the study
and gauge interest.

If the patient is interested in participating, a follow-up phone or Zoom video call will be
scheduled with the patient 7 to 10 days after the initial call and recruitment email is sent.
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Email: One recruitment email will be sent to eligible patients after the study is introduced by phone and
the patient has verbally agreed to receive recruitment email communications. The study team member
will obtain their permission to use email, per the following: “Because URMC can’t control the security of
email messages once we send them, we need your permission to email you. Do you want to receive the
link to the consent via email?”. Permission will be obtained before a PDF of the IRB approved consent
form and study flyer is sent via email for their review.
The email will include a copy of the informed consent; a study flyer; an agreed time for a follow-
up call, to occur either by phone or Zoom video, for the research coordinator to review the consent form
and discuss the patient’s participation further.
While the subject is on the phone, our research coordinator will provide the option of reviewing
the consent form either by phone or via zoom. However, obtained/documented consent will occur in
person as noted in Section 7.
Mail: Mailing the informed consent form with a cover letter that will instruct the potential subject not to
sign/date the consent form as follow up phone or Zoom call will be made by the study coordinator to
review with them. The consent will not be signed/returned via US postal; all consent will be obtained in
person; refer to Section 7. Consent Process.
Flyer: Study flyers will be posted in Kidney Clinic in AC-3 and Highland Hospital clinic waiting area
and restrooms. Subjects who contact the study team directly and leave voice mail will receive follow up
phone call by the study coordinator, per the follow up recruitment phone script submitted for IRB review.
7. CONSENT PROCESS
o Informed consent will be obtained by the research coordinator and documented via a signed
consent form, and stored in a cabinet in a locked room.
o The consent will be obtained in-person when the patient presents to the Kidney Clinic for
their routine follow up.
o To minimize coercion, the research coordinator, and not the patient’s nephrologist, will
explain to the patient the purpose of the study and go over the consent form, and give them
the opportunity to ask questions. The patient will also be given the opportunity to take the
consent form home with them and take as much time needed to look over the consent form.
o If more time is requested by the patient, further follow-ups will occur over the phone to
answer questions, concerns, and discuss participation.
o The research coordinator will ask the patient to summarize the study to ensure their
understanding.
o The Investigator or research coordinator will give a copy of the signed consent form to the
subject and store the original appropriately in a cabinet in a locked room.
o A check-box for consent to contact subjects for future research will be an option with consent for
this study.
Certificate of Confidentiality:
The study is funded by the National Institute of Health, and therefore the Certificate of
Confidentiality (CoC) is automatically included as part of the notice of award. Language
regarding the Certificate of Confidentiality will be included in the consent form.
8. STUDY PROCEDURES
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SCREENING PROCEDURES:
Avmacol ES has not been tested in patients with CKD. Since sulforaphane (SFN) and its metabolites are
cleared by the kidney, to establish a safe dose for our study participants, for Phase I of the study, we will
first perform PK analysis in CKD Stage 3B to 4 patients with eGFR between 25 – 45 mL/min/1.73m2
who meet the inclusion criteria below. The eGFR result should be within a 2 week window at the time of
screening. If eGFR testing was performed longer than 2 weeks, the research coordinator will reach out to
the patient’s provider to ask for repeat testing.
Our research coordinator will use eRecord EMR to screen patients for enrollment based on inclusion and
exclusion criteria listed above in #5. Each week, the research coordinator (RC) will screen subjects
scheduled to visit to the Kidney Clinic in the upcoming 1 to 2 weeks for enrollment. The RC will discuss
with Dr. Le, who will make the final decision for inclusion and exclusion.
If eligible and after subject consent is obtained:
A total of 2 in-person study visits will occur for the Phase I study. The first visit (AC3 or Highland
Hospital) is expected to last for 1 hour. The second visit will only occur at the Clinical Research Center in
Strong Memorial Hospital (SMH) and will take place on day 7 of taking the study drug and is expected to
last up to 9-hours to allow biospecimen collections at 5 separate intervals.
RANDOMIZATION:
As noted in Section 4.1 Study Interventions, groups will be stratified by GSTM1 group, patients will be
assigned randomly to 2 or 4 Avmacol Extra Strength tablets once a day, taken orally with food, as
depicted in Table 1 (below). The groups are categorized into GSTM1 null (GSTM1 (0/0) or GSTM1 non-
null (GSTM1 (1/1) or (1/0)) genotype based on the dominant model we observed in AASK and ARIC
cohorts. We do not anticipate difficulty obtaining the different genotype groups, as 75% of Caucasians
are either GSTM1 (1/1) or (1/0), and 25 % are GSTM1 (0/0). Approximately 65% of patients in our
Kidney Clinic are Caucasians. In African Americans/blacks, approximately 25% are GSTM1 (1/1), 50%
are GSTM1 (1/0), and 25 % are GSTM1 (0/0). Approximately 30% of patients in our Kidney Clinic are
African Americans. Randomization will be performed by the IDS who will be provided the patients’
eGFR and GSTM1 genotypes. Since this is a PK study, the investigators will not be blinded to the
randomization.
Visit 1 (1 hour) at AC3 or Highland Hospital Procedures:
Buccal Swab: A buccal (cheek) swab will be obtained from the subject to extract DNA for GSTM1
genotyping for assignment to groups as outlined in Table 1. (below). Genotyping will be performed as
previously done 2. The processing of DNA and genotyping will be completed within 5 business days.
Drug Dosing: In-person at the time of their study visit, patients in each dose group will be provided 2 or
4 tablets to be taken at home once a day with food for 7 days.
Table 1: Number of Avmacol Extra Strength Tablets
Once a Day
GSTM1 Genotype
2 Tablets
4 Tablets
GSTM1 (1/1 or 1/0)                  6                         6
NIH
PROMIS
GSTM1 (0/0)
6
6
Questionnaire:
For
each
subject, clinical status and symptoms will be monitored using this questionnaire for gastrointestinal
symptoms. Paper copies of this survey will be administered to the subject at Visit 1 and each form is
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expected to take 20 minutes to complete. The questionnaire will be completed in-person as part of Visit 1,
at home on Day 3, and returned with the next in-person visit on Day 7 (Visit 2).
Kansas City Cardiomyopathy Questionnaire (Modified): For each subject, clinical status and
symptoms will be monitored using this questionnaire for heart failure symptoms. Paper copies of
this survey will be provided to the subject at Visit 1 and are expected to take about 30 minutes
each to complete. The questionnaire will be completed in-person as part of Visit 1, at home on Day 3,
and returned with the next in-person visit on Day 7 (Visit 2).
General Questionnaire: Each patient will also complete a brief questionnaire of how they feel each day,
including any new symptoms. Subjects are expected to complete the general questionnaire once each day
throughout the 7-day period.
Subject Tracking Chart: For each subject, a chart will be provided to help track daily study drug intake
and questionnaires. The form will also include the subject’s study drug dosage and 7-day study timeline.
Visit 2/Day 7 Procedures (8-Hours) at Clinical Research Center in Strong Memorial Hospital:
On day 7, subjects will come to the Clinical Research Center at SMH, take their dose with food. This visit
will last for about 8-hours in duration so samples of urine and blood samples can be obtained at scheduled
time intervals. Food and drink will be provided for lunch during the 8-hour visit.
Subjects will be asked to return the drug package so the study team can account for the number of
tablets taken during the 7-day period.
Blood Samples: Blood collection will involve one venipuncture 4 mL blood sample obtained at 0, 1 hour,
2, 4, and 8 hours. The samples may be obtained by a phlebotomist in the Clinical Research Center or
Strong Memorial Hospital Outpatient Lab. An IV-line will be placed for the blood draws to minimize
needle sticks. A total number of two collection attempts will be allowed for each time interval.
Urine Samples: Urine collection will involve one sample of a minimum of 1 mL of urine in a sterile cup
obtained at 0, 1 hour, 2, 4, and 8 hours. Water will be provided between each sample collection.
Blood and urine will be obtained at 5 separate intervals listed above to determine SFN levels in plasma
and urine, respectively. Whole blood, plasma, and urine at each time point will be obtained, frozen, and
stored at -80oC for later processing and analysis. Levels of SFN and its active metabolites will be
analyzed by our Mass Spectrometry Shared Resources Laboratory (MSRL) Core at the University of
Rochester Medical Center.
Medical Record EMR: No research data (GSTM1 genotype or blood SFN level) will be included in the
subject’s medical record. Laboratory data that are part of the patients’ clinical care will be conveyed to
the patients as standard of care. For the study, we will collect demographic information, including age,
sex, height, weight, race, past medical history – specifically history of hypertension, heart failure, and
etiology of kidney disease, if any - and blood pressure data. Research data will not be conveyed to the
patients. While not anticipated, incidental findings that might have health consequences for the individual
subject will be addressed as clinically indicated.
As this is conducted under an IND, the samples will be stored for 2 years after marketing approval or for
5 years, whichever is later. Should additional tests be deemed informative or mechanistic to enhance
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further understanding, we will contact the subjects while samples are still available.
Samples will be destroyed after 5 years.
Genetic Research Procedures: As mentioned above, the GSTM1 null genotype is quite common in
human populations, with 50% Caucasians and 27% African Americans being homozygous for the
GSTM1 (0/0) allele. Whole genomic sequencing will not occur. No genetic counseling will be
provided to the subject. We will genotype GSTM1 to assess whether it influences PK/drug
metabolism of SFN from Avmacol.
Completion of the first phase: To ensure patient safety after they have completed or stopped the study
drug, our research coordinator will call subjects after about 2 weeks to ask how they are feeling, and
whether they have developed any new symptoms. If they have new symptoms, Dr. Le will reach out to
the patient to assess if further evaluation is warranted.
9. RISKS TO SUBJECTS
Sulforaphane/Avmacol ES (Study Drug)
There are some potential risks to participants since we are introducing a well-tolerated study drug in other
clinical trials but has not been previously tested in CKD patients. We take careful precautions by first
establishing an optimal dose of Avmacol ES in CKD patients using reported peak plasma concentrations
in trials that were conducted in patients without kidney disease. Based on the multiple clinical trials that
have been done with Avmacol or the actual sulforaphane compound in other diseases, we do not
anticipate any serious risks. The most common side effects are gastrointestinal, including nausea and
dyspepsia, which are ameliorated when taken with food.
Although not reported in any earlier trial, there is the possibility of an allergic reaction to the
study drug. This reaction may be mild, such as a skin rash, or more severe symptoms like swelling of the
throat, low blood pressure, and shortness of breath. In rare cases, a severe reaction could cause death.
Risks of Blood Draw
The most common risk is pain, bleeding, or bruising at the site of the blood draw. Other risks include
redness, and swelling of the vein and infection, and a rare risk of fainting.
Risks of Buccal Swab
The risk is minimal. There is risk of not obtaining adequate sample for DNA extraction.
Risks of Urine Sample
The risk is minimal. There is risk of spilling urine onto clothes.
Risks of Pregnancy: The effect of sulforaphane on the fetus is not known. The patient will be advised to
immediately stop taking the drug if pregnancy is suspected and notify the research team.
Risk of Disclosure of Privacy and Confidentiality
Other potential risks involve violations of confidentiality. Procedures for assuring confidentiality are
discussed below.
Risks to Social/Emotional Well-Being
We do not anticipate any psychological, social or legal risks beyond those related to participation in a
clinical study.
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Risks of Questionnaires
There are no anticipated risks for subjects to complete the requested questionnaires.
Patients will be informed that declining to participate in this study will not impact their care whatsoever.
10. POTENTIAL BENEFITS TO SUBJECTS
You might not benefit from being in this research study. Your participation will enable us to determine
the best dose for the next study in patients with chronic kidney disease in which you would also be
eligible to participate in.
11. COSTS FOR PARTICIPATION
There is no cost for participation of the study. Avmacol ES will be provided by Nutramax without cost to
the patients.
12. PAYMENT FOR PARTICIPATION
Each of the study participants will receive $100.00 in a prepaid Visa card, divided into two payments of
$50.00 at Visit 1 and Visit 2, as payment for their participation and completion of the study. Subjects who
are withdrawn or voluntarily withdraw from the study due to side effects will also receive the full
compensation of $100.
13. SUBJECT WITHDRAWALS
1. Participants’ decision to withdraw from the study for any reason
2. Development of side effects that are not resolved by dose reduction
3. Failure to adhere to the study protocol
4. Relocation resulting in inability to follow up per protocol
5. Become pregnant
6. New diagnosis of heart failure, cardiovascular event, life threatening infection, or cancer
In the event that a patient drops out the study due to reasons listed above, we will recruit an additional
patient to replace.
Once treatment is stopped for any reason, patients will continue to be followed as part of standard of care
for CKD. Long-term follow up data will continue to be collected, including their blood pressure, eGFR,
and proteinuria.
RETURN OF RESULTS:
Once the study is completed, we will send subjects a summary of the results and what they mean.
Subjects will not receive their own individual results.
14. PRIVACY AND CONFIDENTIALITY OF SUBJECTS AND RESEARCH DATA
The research team consists of URMC clinical providers (Nephrologists) and as such have access to all of
the relevant clinic records. Study data will be collected and managed using REDCap electronic data
capture tools hosted at URMC. Study data will be directly entered into REDCap which is a HIPAA
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compliant database. Only de-identified data will be analyzed, and de-identified data will be stored in a
password protected database only available to the research team.
With regard to patient confidentiality, the risk of improper access, use, or disclosure of participant data is
minimized through the following procedures:
1. All study personnel and researchers are required to sign a pledge of confidentiality, committing to
safeguard the study data during its collection, analysis, and after the study is concluded.
2. Physical (paper) questionnaire forms and media containing the electronic data files will be kept in
locked files with restricted access.
3. Data Key- Each subject will be assigned a study ID number which will be used to label their
data/samples and linked to the subject on a separate key. Only Dr Le and the investigative team
will have access to the data key and it will be stored separately from the dataset.
4. The data upon which statistical analysis will be conducted will contain participant numbers as
unique identifiers in lieu of names, medical record number, or social security numbers. These
data are considered identifiable, but not directly identifiable.
When data generated from this study is shared for analysis, only de-identified information will be
exchanged. No protected health information will be shared with any collaborator nor used in any
publications. Only aggregate results, not individual data, will be published in reports or manuscripts.
15. DATA / SAMPLE STORAGE FOR FUTURE USE
Samples will be collected, processed, and stored for future use in an approved -800C freezer. To minimize
costs, they will be run in batches based on the number of samples that can be loaded on commercially
available kits. As this is conducted under an IND, the samples will be stored for 2 years after marketing
approval or for 5 years, whichever is later. Only Dr. Le and the investigative team will have access to the
stored data and samples.
The investigative team may elect to share with other researchers and/or utilize subject data and
biospecimens collected during this study for future research purposes. This includes subject samples,
health information, and genotype GSTM1 data. Subjects will be provided the opportunity to opt-in or opt-
out of permitting the study team to utilize their data and biospecimens during the ICF process. Should
subjects agree to allow the study team to utilize data and biospecimens for future research, the data and
biospecimens would be used to further understand kidney disease and other related topics.
The clinical data and associated biospecimens will be identified only by the Subject ID used in the current
study. Computers housing the data are secured in locked rooms when not in use. All data files and derived
analytic data files are encrypted for storage and transport. Study data will be kept on password protected
computers at URMC, REDCap and UR Box program. Signed consent forms will be stored in a cabinet in
a locked room.
16. DATA AND SAFETY MONITORING PLAN
Medical Supervision and Surveillance of Study Subjects. The PI, Dr. Le, will be responsible for
supervision of the entire study. Clinical status and symptoms will be monitored using comprehensive
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health screening tools, including the NIH PROMIS questionnaire for gastrointestinal symptoms, and a
modified Kansas City Cardiomyopathy questionnaire for heart failure symptoms that will be relevant to
both patients with a history of heart failure (NY Heart Association Class 3 and 4 heart failure symptoms
are excluded) and patients without pre-existing history of heart failure.
Data Safety Monitoring Board (DSMB). We have already identified 3 members at URMC who are not
investigators in the study to serve on the DSMB:
1. Ronnie Guillet, MD, PhD, Professor of Pediatrics. Over the course of her career, Dr. Guillet has
been involved in two primary areas of research, both focused on better understanding neonatal
development and injury:
neonatal brain injury (neonatal seizures and hypoxic ischemic
encephalopathy) and their treatment and neonatal acute kidney injury (epidemiology, contributing
and ameliorating factors). These efforts and others have resulted in nearly 100 peer reviewed
publications. She has collaborated with colleagues across the country and around the world, has
been invited as a speaker to a variety of regional and national meetings, and has been asked to
collaborate on a number of multicenter clinical trials. In addition, she has chaired 4 Data Safety
Monitoring Committees, including 2 sponsored by NIH NINDS.
2. David Bushinsky, MD, Professor of Medicine, Pharmacology and Physiology. Dr. Bushinsky has
published nearly 120 peer-reviewed articles and over 60 invited reviews, chapters and editorials
focusing on disorders of divalent ion metabolism. He has conducted large clinical trials, including
“The effects of the potassium-binding polymer patiromer on markers of mineral metabolism
(CJASN 2019)”, “Veverimer versus placebo in patients with metabolic acidosis associated with
chronic kidney disease: a multicenter, randomized, double blind, controlled, phase 3 trial (Lancet
2019)”, and “Long-term safety and efficacy of veverimer in patients with metabolic acidosis in
chronic kidney disease: a multicenter, randomized blinded placebo-controlled, 40-week extension
(Lance 2019)”.
3. Dongmei Li, PhD, Associate Professor Public Health Sciences, in the Clinical and Translational
Science Institute (CTSI). She has more than ten years of experience conducting statistical
methodology research, teaching, mentoring public health students, and providing consulting
services for biomedical research. She is serving as Program Director of the Biomedical Data
Science Certificate Program co-sponsored by CTSI and Department of Public Health Sciences.
She also serves as the Biostatistics and Informatics Core Director of an FDA/NCI funded 19
million U54 center grant on flavored tobacco products. For her biostatistics methodology
research, she has worked on both genetic and genomic data analysis (gene expression, SNP, DNA
methylation, ChIP-seq, ATAC-seq, and proteomics) for more than ten years, and has developed
new statistical analysis methods and corresponding analysis packages in R/Bioconductor for
DNA methylation array and RNA-Seq data analysis. She also developed a new method and R
package to control for multiple testing error rates in genomic and genetic data analysis.
The DSMB will meet at the beginning of the Phase I and at the end of Phase I which is anticipated to be
completed in 6 months, and sooner if there are unanticipated side effects and adverse events. The DSMB
will follow the NIH National Center for Research Resources guidelines including:
1. Review subject recruitment, attrition, and minority involvement
2. Monitor safety of research participants by reviewing unblinded data for side effects and
adverse events
3. Assuring compliance with requirements relating to reporting of adverse events
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4. Assuring data accuracy and protocol compliance, and that any action that results in the
temporary or permanent suspension of the protocol is reported to all appropriate monitoring
bodies, including the IRB, and the NIH Office of Biotechnology Activities.
Should any serious adverse event occur, we will convene a meeting with the DSMB to determine whether
the study should be suspended until additional review can be properly performed.
17. DATA ANALYSIS PLAN – To be performed at UVA
Data harmonization, management and analysis
1. Develop data management and statistical analysis plan.
2. Work with the team and CTSI at URMC closely to design a unified management system for data
collection, transfer between the study site and management.
3. Data oversight and monitoring during data collection and integration.
4. Harmonize the study data elements and variables from clinical and laboratory and biochemical
data
5. Validate data quality and perform cleaning process.
6. Work closely with the PI and clinical investigators to determine appropriate statistical methods
and machine learning algorithms for the clinical hypotheses. Cutting-edge statistical methods and
innovative data science tools will be considered or adopted.
7. Prepare the analytical datasets and perform pre-stated statistical analyses.
8. Prepare the final results for manuscript writing and submission, conference presentations and
publications.
The data for safety and feasibility assessment will be summarized descriptively with respect to adverse
events and compliance with Avmacol ES intake. The group-specific data will be summarized and
reported as mean ± SD for continuous measures and as frequency and percentage for categorical measures
and their differences will be compared using two-sample t-tests or Chi-square test.
18. PI oversight for multi-site research
The UR PI will be responsible for the following:
A. Communication: The UR Pi will notify the Site PI of the RSRB site approval and provide
site approval letter as well as copies of the most current version of the study materials via
email. The UR PI is responsible throughout the course of the study to provide all modified
documents and IRB approval letters to UVA site PI.
B. Supervision of study activities at the site: The UR PI will conduct regular meetings with the
site PI to review study activities. Meetings will occur every 3 months or sooner as soon as
any issue arises by zoom. During the meeting, the UR PI will troubleshoot study-related
issues, answer study-related questions, and provide verbal/written direction for all study
activities. Meetings will be documented via meeting minutes in the regulatory binder.
C. Training: The UR PI will ensure that all study personnel have completed required institution-
specific and protocol-specific trainings and that these trainings are documented appropriately
via CITI certification. When study personnel are added/removed, the UR PI will ensure
UVA submits these changes to the local IRB for institutional review and approval. If
applicable, these changes will be appropriately documented on the Delegation of
Responsibilities Log.
D. Reporting: The UR PI will submit required information for reporting, progress reports,
reportable events, non-compliance, Data and Safety Monitoring reports and provide the site
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with any RSRB determinations regarding the submitted reports.
E. Site Files and Documentation: As per Policy 901 Investigator Responsibilities, all sites will
maintain a regulatory file with current and accurate records of all study documentation as
required by applicable regulatory requirements. These files are maintained electronically in
secure BOX URMC servers and shared with study members only.
19. REFERENCES
1.
McCullough, K.P., Morgenstern, H., Saran, R., Herman, W.H. & Robinson, B.M.
Projecting ESRD Incidence and Prevalence in the United States through 2030. J Am Soc
Nephrol 30, 127-135 (2019).
2.
Chang, J., et al. Loss of GSTM1, a NRF2 target, is associated with accelerated
progression of hypertensive kidney disease in the African American Study of Kidney
Disease (AASK). Am J Physiol Renal Physiol 304, F348-355 (2013).
3.
Tin, A., et al. The Loss of GSTM1 Associates with Kidney Failure and Heart Failure. J
Am Soc Nephrol 28, 3345-3352 (2017).
4.
Gigliotti, J.C., et al. GSTM1 Deletion Exaggerates Kidney Injury in Experimental Mouse
Models and Confers the Protective Effect of Cruciferous Vegetables in Mice and
Humans. J Am Soc Nephrol 31, 102-116 (2020).
5.
Liu, H., et al. Biomarker Exploration in Human Peripheral Blood Mononuclear Cells for
Monitoring Sulforaphane Treatment Responses in Autism Spectrum Disorder. Scientific
reports 10, 5822 (2020).
6.
Ye, L., et al. Quantitative determination of dithiocarbamates in human plasma, serum,
erythrocytes and urine: pharmacokinetics of broccoli sprout isothiocyanates in humans.
Clin Chim Acta 316, 43-53 (2002).
7.
Garte, S., et al. Metabolic gene polymorphism frequencies in control populations. Cancer
Epidemiol Biomarkers Prev 10, 1239-1248 (2001).
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ICF_001.pdf: 
RSRB Case Number: 6759
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SCHOOL OF MEDICINE & DENTISTRY
Department of Medicine
Nephrology Division
MEDICINE of THE HIGHEST ORDER
CONSENT FORM
Safety and Efficacy of Avmacol ES in Chronic Kidney Disease: First Phase
Principal Investigator:  Thu H. Le, MD
This consent form describes a research study, what you may expect if you decide 
to take part and important information to help you make your decision. Please 
read this form carefully and ask questions about anything that is not clear before 
you agree to participate. You may take this consent form home to think about and 
discuss with family or friends.
Key Information
•
Being in this research study is voluntary – it is your choice.  
•
You are being asked to take part in this study because you are an adult who have 
been clinically diagnosed with chronic kidney disease for which there is no cure, and 
you may or may not progress to end stage kidney disease. 
•
The purpose of this study is to determine dosage, safety, and adverse events related 
to the investigational drug Avmacol Extra Strength (ES) being studied in patients 
with chronic kidney disease (CKD).  The drug is being studied to determine if it can 
decrease kidney disease progression rate and improve levels of antioxidants and 
inflammation in patient with chronic kidney disease (CKD).
•
Your participation in this study will last for 7 days or less if you develop serious side 
effects or have side effects to Avmacol ES that cannot be helped by reducing the 
dose. 
•
Study procedures will include two in-person study visits.  The first visit will last about 
one hour and include a cheek swab to extract DNA, receive questionnaires, and 
obtaining the study drug to be taken at home over a 7-day period. The second visit 
(day 7) will last for 8 hours and involve collection of urine and blood samples at 
different time intervals during the 8-hour period. This visit will take place at Strong 
Memorial Hospital with food and beverage provided. Outside of the in-person study 
visits you take the study drug (tablets) at home as instructed and complete 
questionnaire. Additionally, information from your medical record will be obtained for 
the study.   
•
There are risks from participating. 
o
The most common risks with the study drug Avmacol ES, are side effects of 
headache and gastrointestinal, including nausea and indigestion, which are 
lessened or prevented when taken with food. 
o
The most serious risk for Avmacol ES is the possibility of allergic reaction. See 
the “Risks of Participation” section in this consent form for more information. 
You should discuss these risks in detail with the study team.
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•
You might not benefit from being in this research study.
Purpose of Study 
The purpose of this study is to test the safety of drug (Avmacol ES) to determine if it can 
decrease kidney disease progression rate, decrease markers of oxidative stress, and 
inflammation that is usually high in patients with kidney disease. 
The study drug Avmacol ES is a commercially available as a supplement however, it 
has never been tested in patients with kidney disease.  Avmacol has not been approved 
by the Food and Drug Administration (FDA) for treatment of chronic kidney disease and 
is therefore investigational for the purpose of this study. 
This is a phase 1 drug study which is being done to establish a safe dose for patients with 
chronic kidney disease based on blood levels of the drug.  We will also obtain your DNA 
to determine if you have a gene (GSTM1) that affects the clearance of the drug; no other 
genetic testing will be done on your DNA sample.  Up to 50 percent of human populations 
do not express this gene.      
If proven to be well tolerated, this phase of the study will determine the best dose for the 
next study phase.   
Description of Study Procedures
Your participation in the study will be 7 days or less if you develop serious side effects 
or have side effects that cannot be mitigated by dose reduction.  
 
Medical Record Data:  A member of the study team will access your medical record to 
collect information about your age, sex, race, height and weight, medications you are 
taking, and the results of any laboratory or diagnostic tests. For eligibility purposes, if you 
are of childbearing potential, you will be asked to complete a urine pregnancy test before 
taking the study drug.
DNA sample:  After you consent, a buccal (cheek) swab will be obtained to extract 
DNA to determine if you have or don’t have the GSTM1 gene that can metabolize the 
drug.  We will only determine whether or not you have the GSTM1 gene that may 
influence the metabolism of the drug.   We will not look at any other gene, such genetic 
risk for cancer. The result of whether you have the GSTM1 gene will NOT be recorded 
in your medical record.  We will store your DNA sample for 5 years unless we receive 
your request for us to discard your sample sooner. Your request can be by simple 
phone call, in person, or by email to our study team.
   
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Visit 1:  
This visit may occur at Strong Memorial Hospital AC3 or Highland Hospital and will take 
about one hour to complete. The following procedures will occur at this visit:
Drug Dosing: You will be randomized (like the flip of a coin) to take either 2 tablets or 4 
tablets of the study drug once a day for 7 days.  
Questionnaires: You will be provided instructions and 3 paper questionnaires to take 
home and fill out. Each questionnaire will be completed at Visit 1 and as noted below:
•
General Questionnaire: Includes questions about how you are feeling, if you 
experience any new symptoms. Completed daily for the 7-day period.
 
•
Gastrointestinal Questionnaire: Includes questions about symptoms.  Completed 
on Day 3 and Day 7.
•
Kansas City Cardiomyopathy Questionnaire: Includes questions about heart 
failure symptoms.  Completed on Day 3 and Day 7.
Tracker: A chart will be provided to help you track daily study drug intake and 
questionnaires. This form will also include study drug dosage and 7-day study timeline.
At Home Procedures: At the end of visit 1, you will be given the study drug.  
questionnaires, and the tracker to take home. You will take the assigned drug dosage 
once daily as instructed. You will also complete the study questionnaires on the 
designated day(s), as instructed. 
Visit 2: 
On day 7, you will come to the Clinical Research Center (CRC) in Strong Memorial 
Hospital.  Visit 2 will take about 8-hours to complete with food and beverage provided 
during this period. 
You will need to bring your last dose of the study drug with the package, along with the 
all the study questionnaires, and the tracker sent home with you at visit 1. The following 
procedures will occur with Visit 2:
Drug Dose: You will take your study drug dose with food in front of a study coordinator.
Blood Draw: You will have blood drawn through a vein in your arm or hand at 5 separate 
intervals; immediately after you take the medication, at 1 hour, 2 hours, 4 hours and 8 
hours after. An IV-line will be placed for the blood draws to minimize needle sticks. You 
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are free to leave in between blood collection times. Approximately 4 mL (just slightly more 
than a teaspoon) of blood will be obtained each time. 
Urine Sample: You will also a urine sample occur immediately after each blood draw. 
Approximately 1 milliliter of urine will be obtained each time in sterile cup. 
Information about your study participation and study results may be included in your 
electronic health record. If you have concerns about this or to obtain more detail, you 
should discuss this with the study team.
Number of Subjects:
Approximately 24 subjects with chronic kidney disease will take part in this study.  
Risks of Participation 
Avmacol ES - Study Drug:  While Avmacol has been well-tolerated in other clinical trials 
such as for autism, chemotherapy drug toxicity, it has not been previously tested in 
patients with kidney disease. The potential risks are side effects. The most common side 
effects are headache and gastrointestinal, including nausea and indigestion, which are 
lessened or prevented when taken with food. Since Avmacol has a short half-life, we 
expect the side effects would be short-lived when the drug is stopped. 
Based on the multiple clinical trials that have been done with Avmacol or the actual 
sulforaphane compound in other diseases, we do not anticipate any serious risks.
Although not reported in any earlier trial, it is possible that you may have an allergic 
reaction to the study drug. This reaction may be mild, such as a skin rash, or you may 
have more severe symptoms like swelling of the throat, low blood pressure, and shortness 
of breath. In rare cases, a severe reaction could cause death.
Blood Draws:  Blood draws may cause pain, redness, bruising or infection at the site of 
the needle stick.  Rarely some people faint.  The study team member may apply 
numbing cream to the area so that the needle stick won’t hurt as much.
Buccal (cheek) Swab:   The risk associated with this procedure are minimal.  
Urine Sample:  The risk is minimal. There is risk of spilling urine onto clothes during your 
collection.
Pregnancy: The effect of sulforaphane on the fetus is not known. If you think you may be 
pregnant, please immediately stop taking the drug and notify the research team. 
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Risks of Questionnaires: There are no anticipated risks for you to complete the 
requested questionnaires other than the time it takes to complete them. If any questions 
make you uncomfortable, you may skip them or stop any time.
Risks to Social/Emotional Well-Being: We do not anticipate any psychological, social 
or legal risks beyond those related to participation in a clinical study.  
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, 
(NCT05153174) as required by U.S. Law. This Web site will not include information that 
can identify you.  At most, the Web site will include a summary of the results. You can 
search this website at any time. 
The study team may be notified if you receive other health care services at URMC or its 
Affiliates (e.g., visit to the emergency room). In addition, the following individuals may 
know you participated in research and may see results of testing conducted for this 
study:

Staff at the University of Rochester Medical Center and its Affiliates (e.g., Strong 
Memorial Hospital, Highland Hospital, URMC primary care, specialist physician 
offices) who have a reason to access your electronic health record. 

Health care providers who are involved in your care at a facility that is not part of 
the University of Rochester Medical Center and its Affiliates and who have 
reason to access your electronic health record.

Individuals who request a copy of information from your health record for 
activities such as treatment or payment (e.g., medical insurance companies, 
worker’s compensation).
Benefits of Participation 
You might not benefit from being in this research study.  Your participation will enable 
us to determine the best dose for the next study in patients with chronic kidney disease 
in which you would also be eligible to participate in.  
Compensation for Injury 
If you are directly injured by Avmacol ES, or by medical procedures needed because of 
this study, and you receive medical care for the injury, you may need to pay for that 
care.  You will be reimbursed for reasonable and necessary medical costs for such 
care, but you might not be reimbursed for care covered and paid for by a third party like 
your health insurance provider, or costs such as required co-payments or deductibles 
related to that coverage.  No other funds have been set aside to pay for such things as 
lost wages or expenses due to a current underlying illness or condition.
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If your research injury is paid for by the University, we will collect your name, date of 
birth, gender, and Medicare Health Insurance Claim Number or Social Security Number 
to determine your Medicare status. This information will be used only in accordance with 
the law. If you are a Medicare beneficiary, information about the study you are in, and 
any payments made related to your injury, will be reported to the Centers for Medicare 
& Medicaid Services (CMS), in accordance with CMS requirements.  This information 
will not be used for any other purpose.
Costs 
There will be no cost to you to participate in this study. 
Payments 
You may be paid up to $100.00 for your participation in the study via a prepaid Visa 
card: 
Visit 1: $50.00
Visit 2: $50.00
Expect up to 4-6 weeks for the prepaid card to be processed and mailed after the 
completion of each study visit.
Confidentiality of Records and Authorization to Use and Disclose Information for 
Research Purposes 
The University of Rochester makes every effort to keep the information collected from you 
private. We will not label your data/samples with identifying information about you, such 
as your name, medical record number or social security number.  We will label your 
data/samples with a unique ID# and store your identifying information linked to the code 
in a separate document. All data/samples will be stored in a secure manner. 
Sometimes, however, researchers need to share information that may identify you with 
people that work for the University, regulators or the study sponsor.  
If you have never received a copy of the University of Rochester Medical Center (URMC) 
and Affiliates Notice of Privacy Practices, please ask the investigator for one. 
What information may be used and given to others?
The study doctor will get your personal and medical information.  For example: 

Research records

Records about phone calls made as part of this research

Records about your study visits

Past and present medical records related to the study, including records of external 
providers that are available via your electronic health record at URMC & Affiliates    

Results of medical tests  
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Who may use and give out information about you?

The study doctor and the study staff

URMC and Affiliates
Your information may be given to: 

The Department of Health and Human Services

The University of Rochester

University of Virginia, to share de-identified data

National Institute of Health (NIH) who is the sponsor for this study (they provide 
funding to conduct the study). 

Nutramax who provides the study drug 

The U.S. Food and Drug Administration (FDA) may also need to inspect study 
records at some point during the study or even after it has been completed.  In the 
event that this should occur, every effort will be made to keep identifying 
information about you private. 
Why will this information be used and/or given to others?

To do the research 

To study the results 

To see if the research was done correctly  
If the results of this study are made public, information that identifies you will not be used.
What if I decide not to give permission to use and give out my health information?
Then you will not be able to be in this research study.
May I review or copy my information?
Yes, but only after the research is over.
How long will this permission be valid?
This permission will last indefinitely. 
May I cancel my permission to use and disclose information?
Yes. You may cancel your permission to use and disclose your health information at any 
time.  You do this by sending written notice to the study doctor.  Upon receiving the written 
notice, the study team will no longer use or disclose your health information and you will 
not be able to stay in this study.  Information that has already been gathered may need to 
be used and given to others for the validity of the study.  
May I withdraw from the study?
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Yes. If you withdraw your permission to be in the study, no new health information 
identifying you will be gathered after that date.  Information that has already been 
gathered may still be used and given to others.  
Is my health information protected after it has been given to others?
No. There is a risk that your information will be given to others without your permission.
Future Use of Information/Samples
Your information and samples might be distributed or used for future research studies 
without additional informed consent.  All identifiers will be removed before your 
information and samples are used or distributed. You will be given the option at the end 
of this consent form to decide if you would like your information or samples used for 
future research. 
Circumstances for Dismissal 
You may be withdrawn from the study if you do not keep appointment for study visits or 
if you cannot complete study activities. You also may be withdrawn from the study if 
your disease becomes worse or if your doctor feels that participating in the study is 
harmful to your health, if you become pregnant, or if you have a new diagnosis such as 
advanced heart failure, cardiovascular event, life threatening infection, or cancer.
Completion of the first phase 
To ensure your safety after you have stopped the study drug, our research coordinator 
will call after about 2 weeks to ask how you are feeling, and whether you have 
developed any new symptoms.   
As noted, this is a phase 1 study being done to establish a safe dose of Avmacol ES for 
patients with chronic kidney disease. Once you complete this phase of the study, you 
may be eligible to participate in the next phase (Phase 2) of the study which is expected 
to last about 6 months.
New Study Information 
If we discover any new information that is clinically relevant, we will let you know.
Sponsor Support 
The University of Rochester is receiving funding support from the National Institutes of 
Health (NIH) for conducting this research study.
Commercial Profit 
We will use your information and/or samples for research only. However, the results of 
this research might someday lead to the widespread use of sulforaphane in the 
treatment of chronic kidney disease. You will not receive money from the sale of 
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sulforaphane.
Return of Research Results 
In general, we will not give you any individual results from your participation in the 
study. If we find something of urgent medical importance to you, we will inform you, 
although we expect that this will be a very rare occurrence.
You will not receive your individual results.
Some things you should know about the results: 

While we expect to have an idea of how kidney function level will affect the 
metabolism of the drug, it is possible the results will difficult to interpret. 

For the genetic part of this study, we will only determine whether or not you have 
the GSTM1 gene that may influence the metabolism of the drug.   We will not 
look at any other gene.  
Certificate of Confidentiality 
To help us further protect your privacy, the investigators have a Certificate of 
Confidentiality from the Department of Health and Human Services (DHHS). 
With this Certificate, the investigators cannot be forced (for example, by court 
subpoena) to disclose or use research information, documents, or samples that may 
identify you in any Federal, State, or local civil, criminal, administrative, legislative, other 
proceedings, or be used as evidence. Disclosure will be necessary, however, upon 
request of DHHS for audit or program evaluation purposes, or to other government 
agencies related to communicable diseases. 
You should understand that a Certificate of Confidentiality does not prevent you or a 
member of your family from voluntarily releasing information about yourself or your 
involvement in this research. If an insurer, employer, or other person obtains your 
consent to receive research information, then the investigator may not use the 
Certificate to withhold that information. This means that you and your family must also 
actively protect your own privacy.
Finally, you should understand that the investigator is not prevented from taking steps, 
including reporting to authorities, to prevent serious harm to yourself or others.  Include 
the following only if applicable: The Certificate of Confidentiality will not be used to 
prevent disclosure to state or local authorities of child abuse and neglect, or serious 
harm to the subject or others.
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Contact Persons
For more information concerning this research or if you feel that your participation has 
resulted in any research related injury, emotional or physical discomfort, please contact: 
Dr. Thu Le at 585-275-1554 or the nephrologist on call after regular hours.
Please contact the University of Rochester Research Subjects Review Board at 265 
Crittenden Blvd., CU 420628, Rochester, NY 14642, Telephone (585) 276-0005 or 
(877) 449-4441 for the following reasons:

You wish to talk to someone other than the research staff about your rights as 
a research subject;

To voice concerns about the research;

To provide input concerning the research process;

In the event the study staff could not be reached.
Voluntary Participation
Taking part in this study is voluntary. You are free not to take part or to withdraw at any 
time, for whatever reason.  No matter what decision you make, there will be no penalty 
or loss of benefit to which you are entitled.  In the event that you do withdraw from this 
study, the information you have already provided will be kept in a confidential manner.
This will not affect the care you receive for chronic kidney disease.  
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RSRB Case Number: 6759
Page 11 of 12
Version Date: 01/05/2022 Mod Date 06Dec2022
CONSENT TO FUTURE USE OF INFORMATION / SAMPLES 
May we share your samples, health information, and genotype data with other 
researchers who study kidney disease?
Yes             No
May we share your samples, your GSTM1 data, and health information with other 
researchers for future research projects related to other topics?
Yes       
No
CONSENT TO RE-CONTACT 
May your study doctor, or someone from the study team, contact you in the future about 
using your samples or information for research that is not described in this consent 
form?
Yes       
No
May your study doctor, or someone from the study team, contact you in the future to 
see if you would like to participate in other research?
Yes       
No
RSRB Approval Date: 12/9/2022
Expiration Date: 12/5/2023


RSRB Case Number: 6759
Page 12 of 12
Version Date: 01/05/2022 Mod Date 06Dec2022
SIGNATURES/DATES 
After reading and discussing the information in this consent form you should 
understand:

Why this study is being done;

What will happen during the study;

Any possible risks and benefits to you;

Other options you may have instead of being in the study; 

How your personal information will be protected;

What to do if you have problems or questions about this study.
Subject Consent
I have read (or have had read to me) the contents of this consent form and have been 
encouraged to ask questions.  I have received answers to my questions.  I agree to 
participate in this study.  I have received (or will receive) a signed copy of this form for 
my records and future reference.
Subject Name (Printed by Subject)
Signature of Subject
Date
Person Obtaining Consent
I have read this form to the subject and/or the subject has read this form.  I will provide 
the subject with a signed copy of this consent form.  An explanation of the research was 
given and questions from the subject were solicited and answered to the subject’s 
satisfaction.  In my judgment, the subject has demonstrated comprehension of the 
information.  I have given the subject adequate opportunity to read the consent before 
signing.
Name and Title (Print)
Signature of Person Obtaining Consent
Date
RSRB Approval Date: 12/9/2022
Expiration Date: 12/5/2023