Conditions: Chronic Kidney Diseases Hyperkalemia
Keywords: Chronic kidney disease, stages 3B-4
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 3
Healthy volunteers: no

Brief summary:
The purpose of this proof-of-concept controlled-feeding study is to determine whether patiromer (Veltassa®, Relypsa, Inc., Redwood City, CA) can be used to maintain normal serum potassium concentrations in chronic kidney disease (CKD) patients who are transitioned to a plant-rich diet.

Detailed description:

Arms:
arm 1: During the first phase (week 2), participants will be transitioned to a plant-rich renal diet, which contains moderate protein (10-15% of kcal), restricts dairy products (less than or equal to 1 serving/day), and eliminates high-potassium fruits and vegetables.

During the second phase (weeks 3 and 4), the diet will be altered to provide at-least half of fruits and vegetables from high-potassium sources.

Interventions: intervention 1: Patiromer intervention 2: Research Diet Menu
Intervention descriptions: intervention 1: Patiromer dosing will be determined based on fasting potassium concentrations measured at the end of each week, factoring in both the absolute concentration, as well as the rate of change. The baseline dose of patiromer will correspond to the study by Weir et al. (2015); 8.4-g once per day for participants with a baseline serum potassium of greater than or equal to 5.1 mEq/L. intervention 2: During the study, participants will be asked to consume only the foods provided in the research diet

Protocol document:
Prot_SAP_000.pdf: 
Protocol Version 6 – 07.10.2019 
Principal Investigator: David Goldfarb, MD 
Study Number: 17-00051 
NCT Number: NCT03183778 
 
1)  Protocol Title  
Use of patiromer to transition chronic kidney disease patients with hyperkalemia to a plant-rich diet 
 
2)  Objectives  
The purpose of this proof-of-concept controlled-feeding study is to determine whether patiromer (Veltassa®, 
Relypsa, Inc., Redwood City, CA) can be used to maintain normal serum potassium concentrations in chronic 
kidney disease (CKD) patients who are transitioned to a plant-rich diet. We hypothesize that patriomer can be 
titrated to maintain serum potassium concentrations in the normal range, allowing CKD patients to consume a 
plant-rich diet without developing hyperkalemia. If successful, we plan to conduct a randomized clinical trial to 
determine the quality of life and health outcomes of CKD patients with hyperkalemia undergoing an intensive 
behavioral intervention to promote a low-potassium diet, or a plant-rich diet plus patiromer. 
 
3)  Background  
An estimated 22.5% of adults 60 years and older in the U.S. have stages 3-5 CKD1. Individuals with stages 
3-5 CKD are at increased risk of high blood potassium concentrations (hyperkalemia), which in severe cases 
can disrupt the normal contractility of the heart2. Several factors are thought to contribute to hyperkalemia in 
CKD patients, in particular diabetes, dietary potassium intake, and medications that inhibit the renin-
angiotensin-aldosterone system (RAAS inhibitors, which include angiotensin converting enzyme inhibitors and 
angiotensin 2 receptor blockers; ACEi and ARBs)3,4. Given the potential health consequences of hyperkalemia, 
stages 3-5 CKD patients, even those without hyperkalemia, are often directed to follow a low-potassium diet4.  
Unfortunately, following a low-potassium diet involves limiting or avoiding many plant-based sources of 
potassium, including nuts, seeds, legumes, and high-potassium fruits and vegetables. With accompanying 
dietary restriction requirements for sodium, phosphate and protein, the diet can be burdensome and unpalatable 
for the patients, and can make it difficult to obtain essential nutrients4. In addition to providing potassium, high-
potassium plant foods are important sources of dietary fiber, organic anions (potential base), antioxidants and 
other phytochemicals (e.g., phytosterols), and therefore, a low-potassium diet may contribute to hypertension 
(low potassium), constipation and diarrhea (low fiber), dysglycemia and dyslipidemia (low fiber and other 
phytochemicals), metabolic acidosis (low organic anions), oxidative stress and inflammation (low antioxidants 
and other phytochemicals)4.  
Patiromer is approved by the U.S. Food and Drug Administration (FDA) for the treatment of hyperkalemia, 
and has been demonstrated to be effective in treating hyperkalemia in CKD patients5. However, the potential of 
this new therapy for allowing CKD patients to liberalize their diets, and the potential health benefits of 
following a plant-rich diet in advanced CKD are yet unexplored.  
 
4) Inclusion and Exclusion Criteria  
The focus of the study is to: a) evaluate the efficacy of patiromer for managing serum potassium 
concentrations in CKD patients as they are transitioned to a plant-rich diet that includes high-potassium fruits 
and vegetables, and b) evaluate the impact of a plant-rich diet on health outcomes in CKD patients. We will 
recruit 10 CKD patients with persistently elevated serum potassium concentrations in New York City. 
i. Inclusion criteria. In order to be eligible for the study, the individual must meet the following criteria: 
a) 19-80 years of age 
b) Stages 3-4 CKD (estimated glomerular filtration rate (eGFR) of 15-59 mL/min/1.73m2, not 


Protocol Version 6 – 07.10.2019 
treated with dialysis) 
c) No prior treatment with patiromer 
d) Mild hyperkalemia (potassium 5.1 to <6.5 mEq/L) on one of the last two blood tests 
e) No prior episodes of moderate-severe hyperkalemia (potassium ≥6.5 mEq/L) in the past 6 
months 
f) Deemed appropriate for the intervention by the patient’s nephrologist, considering the 
patient’s prognosis, cognition and pending treatments (e.g., dialysis)  
ii. Exclusion criteria. We will exclude from participation patients with the following characteristics: 
a) Change in medications that alter potassium homeostasis (e.g., RAAS inhibitors, diuretics, -
blockers) in the last month 
b) Diagnosed with bowel diseases or syndromes (e.g., bowel obstruction, major GI surgery, 
short-bowel syndrome, irritable bowel syndrome, inflammatory bowel disease, chronic diarrhea)  
c) Dietary restrictions (e.g., allergies) or otherwise unable/unwilling to adhere to study diets 
(excludes dietary restrictions on high-potassium foods) 
d) Pregnant (females) or planning to become pregnant (males and females) during the study 
If at any point during the study (including baseline) a participant has moderate-severe hyperkalemia 
(potassium ≥6.5mEq/L), or if a participant becomes pregnant during the study, they will be withdrawn from the 
study. 
Inclusion of women and minorities 
Given the pilot nature of the intervention and small sample size (n=10), the study population will not be 
representative of the CKD population, and will have insufficient power to detect differences in intervention 
effects by sex and race/ethnicity. To our knowledge, plant-rich diets, such as those being investigated in this 
study, have similar health effects by sex and race/ethnicity. No individual will be excluded from the study on 
the basis of sex or race/ethnicity alone, and we will attempt to obtain a sample that reflects the demographics of 
our source population.  
 
5) Study-Wide Number of Subjects  
We will recruit a total of 10 individuals to the study. We have secured the support of the New York Harbor VA 
Healthcare System, which served approximately 250 non-dialysis CKD patients in the New York City area, as 
well as the Division of Nephrology at NYU Langone Health. It is estimated that approximately 10% of these 
patients have hyperkalemia. Thus, we have no concerns about our ability to access and recruit the required 
number of participants for this study. The estimate demographic breakdown of patients at the renal clinic are 
95% male with 40% white, 25% black, 20% Hispanic, 10% Asian, and 5% other racial/ethnic background. The 
planned enrollment is outlined in Table 1.   
 
Table 1. Planned enrollment report 
 
 
Racial Categories 
Ethnic Categories 
 
 
Total 
Not Hispanic or Latino 
Hispanic or Latino 
Female 
Male 
Female 
Male 
American Indian/  
Alaskan Native 
0 
0 
0 
0 
0 
Asian 
0 
1 
0 
0 
1 
Native Hawaiian or  
Other Pacific Islander 
0 
0 
0 
0 
0 
Black or African American 
0 
2 
0 
1 
3 
White 
1 
3 
0 
1 
5 


Protocol Version 6 – 07.10.2019 
More than 1 race 
0 
1 
0 
0 
1 
Total 
1 
7 
0 
2 
10 
 
6) Study-Wide Recruitment Methods  
Potential participants will be identified using two recruitment methods: 1. Referral by the patient’s 
nephrologist, and 2. DataCore directed search of electronic medical records. Nephrologist referral patients will 
be obtained from the New York Harbor VA Healthcare System, NYU Langone Health, and Bellevue Hospital. 
The DataCore directed search of electronic medical records will be limited to patients of nephrologists in the 
Division of Nephrology who have an episode of mild hyperkalemia in the past 6-months. Once identified using 
the electronic medical record search, the patient’s nephrologists will be notified about their potential eligibility. 
Per the study inclusion criteria, nephrologists will be asked to confirm that the patient is appropriate for the 
study.  
(a) Dr. Goldfarb or Margaret Curran will review each section of the written consent form with the 
referred participant, ask the participant if they understand each section, and clarify any questions 
they may have. The participant and the person obtaining consent will sign and date the consent form. 
Copies of the consent, which includes the contact information of the PI (Goldfarb), will be provided 
to the participant and sent to the patient’s nephrologist. Informed consent will be considered an 
ongoing process throughout the study, and participants’ questions regarding their rights and 
responsibilities will be addressed whenever they occur.  
(b) Once enrolled, Dr. Goldfarb and Margaret Curran will meet to verify that the participant meets the 
inclusion/exclusion criteria. This information will be obtained from the patient’s electronic medical 
record. 
(c) Study staff will contact eligible patients, and schedule a fasting screening appointment (at least 8 
hours of fasting). 
A fasting blood sample will be obtained at the screening visit, and analyzed for potassium. If this test is in 
the range of mild hyperkalemia (potassium 5.1 to <6.5 mEq/L), the participant will be deemed to have persistent 
hyperkalemia, and be accrued. Otherwise they will be deemed ineligible, and excluded from the study. 
Regardless of enrollment status, all eligible patients who are invited to participate in the study will be 
reimbursed $25.00 for time and travel expenses incurred by attending the screening visit.  
 
7) Study Timelines  
We will recruit 10 participants. Given the intensiveness of the intervention, no more than two participants will 
be enrolled in the intervention at a time.  
 
8) Study endpoints  
Among 10 stages 3-4 CKD patients with persistent, mild hyperkalemia, we will evaluate, in a quasi-
experimental, controlled feeding study, the efficacy of patiromer for maintaining normal serum potassium 
concentrations when following a plant-rich diet that includes high-potassium fruits and vegetables, as well as 
the effects of this diet on health outcomes. The participants will be transitioned gradually to a plant-rich diet, as 
outlined further below.  
The interventions will be evaluated primarily in terms of serum potassium concentrations, but health 
outcomes will also be assessed, including blood pressure, gastrointestinal symptoms, and fasting concentrations 
of phosphorus, calcium, magnesium, albumin, glucose, insulin, cholesterol, LDL-cholesterol, HDL-cholesterol, 
triglycerides, urea nitrogen, bicarbonate and C-reactive protein. For all parameters, baseline values will be 
compared to values at the end of each diet phase (weeks 2 and 4). 
 


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9) Procedures involved  
a. Design. 
We will conduct an unblinded, quasi-experimental, controlled feeding study, which will be coordinated 
through the New York University – Health and Hospitals Corporation Clinical and Translational Science 
Institute (CTSI). Throughout the study, participants will be prescribed patiromer by the study nephrologist 
(D.S.G.), which will be administered through the CTSI pharmacy. After a 1-week stabilization period, in which 
participants are prescribed Patiromer while following their usual diets, the feeding component of the study will 
occur in two phases. During the first phase (week 2), participants will be transitioned to a plant-rich renal diet, 
which contains moderate protein (10-15% of kcal), restricts dairy products (1 serving/day), and eliminates 
high-potassium fruits and vegetables. During the second phase (weeks 3 and 4), the diet will be altered to 
provide at-least half of fruits and vegetables from high-potassium sources. To reduce participant burden, meals 
will be delivered to participants by Portable Chef (New York, NY) three times per week.   
i. Patiromer. Patiromer dosing will be determined based on fasting potassium concentrations measured at 
the end of each week, factoring in both the absolute concentration, as well as the rate of change. The baseline 
dose of patiromer will correspond to the study by Weir et al. (2015); 8.4-g once per day for participants with a 
baseline serum potassium of 5.1 mEq/L. The following dosing schedule (Table 2) will be used for managing 
hyperkalemia during the study: 
Table 2. Dosing of patiromer during the study based on serum potassium concentrations 
Potassium 
Change in Potassium 
Action  
<3.8 mEq/L 
Same or decreased 
Contact study nephrologist to determine dose 
<3.8 mEq/L 
Increased 
Continue with current dose 
3.8-5.0 mEq/L 
Changed <0.5 mEq/L 
Continue with current dose 
3.8-5.0 mEq/L 
Changed ≥0.5 mEq/L 
Continue with current dose, but notify study nephrologist 
5.1-6.0 mEq/L 
Decreased 
Continue with current dose 
5.1-6.0 mEq/L 
Same or increased 
Contact study nephrologist to determine dose 
>6.0 mEq/L 
Decreased 
Continue with current dose, but notify study nephrologist 
>6.0 mEq/L 
Same or increased 
Contact study nephrologist to determine dose 
ii. Research Diets. The guidelines for research diets are outlined in Table 3. With the exception of the Dairy 
Food Group, diets will be balanced according to the USDA MyPlate. Diets will be based on a 7-day menu 
cycle, and will be reviewed by participants during the screening visit. In order to promote participant adherence 
with the diets, participants will be permitted to select appropriate substitutes based on their food preferences 
from a list of pre-approved substitutes. For example, if a participant does not like to eat apples, they may 
substitute this for a list of other low-potassium fruits.  
Diets will be designed to match a participant’s estimated energy requirements based on resting energy 
expenditure (REE) determined by Mifflin St. Joer equation multiplied by 1.4 to account for thermal effect of 
food, and physical activity. As a precaution, two small snacks (~100 kcal) that are low in potassium will be 
provided along with meals, and the prescribed research diet will be adjusted on the subsequent delivery, if 
needed. Participants will be directed to consume the foods provided, and record any deviations from the 
prescribed diets. As the intent of the study is not to modify fluid or sodium intake, participants will be 
encouraged to consume water, and use table salt as per their usual practices. Because coffee and tea are high in 
potassium, participants will be directed to limit their intake to no more than one cup per day. 
Research diet prescriptions will be generated by the study coordinator (M.C.), and prepared and delivered to 
participants by Portable Chef, a commercial kitchen located in Manhattan that specializes in providing catered 
meal plans. Meals will be prepared from scratch, using a commercial food scale (TE10FT, Taylor Precision 
Products, Inc., Oak Brook, IL). Any food items that may undergo commercial processing (e.g., enriched meats) 
will be carefully selected to ensure that they contain no added sodium, phosphorus or potassium. To ensure the 


Protocol Version 6 – 07.10.2019 
privacy of participants, staff at Portable Chef will not be provided any participant information, apart from their 
name, address and phone number, which are necessary to coordinate meal deliveries.  
 
 


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Table 3. Dietary guidelines for research diets 
Food Group 
Low-K Plant-rich Diet 
Liberalized Plant-Rich Diet 
Protein Foods 
• ¼ animal, ¾ plant 
• ¼ animal, ¾ plant 
Grain Products 
• ½ refined, ½ whole grain 
• ½ refined, ½ whole grain 
Dairy Foods 
• 1 serving/day 
• 1 serving/day 
Fruits & Vegetables 
• Low-K only 
• ½ low-K, ½ high-K 
K, potassium 
 
b. Measures. Unless otherwise noted, measurements occur at baseline, and at the end of phase I (week 1) and 
phase II (week 3). With the exceptions of patiromer dose (obtained from the CTSI Pharmacy) and data obtained 
from the participant’s medical charts, study measurements will be obtained during visits to the CTSI Clinical 
Research Center (CRC) at Bellevue Hospital. A summary of study visits and procedures is provided at the 
bottom of this section (Table 4). 
i. Screening measurements. At the screening measurement visit, a fasting blood sample will be collected 
and analyzed for serum potassium concentrations. In addition, height and weight will be measured by study 
staff at the CTSI using a stadiometer and balance scale, respectively for estimating energy requirements (see 
9.ii.) 
ii. Baseline measurements. In addition to the outcome measures (described in detail below), key 
information used to characterize the patient population and/or control for as covariates, will be collected at 
baseline through questionnaires, review of patients’ medical charts and clinical measurements. Questionnaires 
will be self-administered, and will include questions on diagnosis with diabetes and hypertension, 
race/ethnicity, sex, age, income, education, employment, tobacco and alcohol use, use of dietary supplements 
and urine output. Data collected from medical charts will include cause of CKD, diagnosis of diabetes and 
hypertension (for comparison to and verification of self-report), urine albumin concentration, prescriptions for 
vitamin D, antihypertensives, hypoglycemic agents, insulin, and phosphorus binders. Variables that may change 
during the intervention, including body weight and medications, will also be assessed at the end of phase I 
(week 2) and phase II (week 4).  
ii. Usual dietary intake. Usual dietary intake of participants will be assessed during the stabilization period 
(week 1). Participants will be asked to maintain a 3-day food record, which includes two weekdays, and one 
weekend day. Food records will be reviewed with the study coorindator (M.C.) at the end of the stabilization 
period to ensure accuracy. 
iii. Serum potassium concentrations. The primary purpose of this study is to evaluate the efficacy of 
patiromer for maintaining serum potassium concentrations in CKD patients during transition to a liberalized 
plant-rich diet by comparing fasting serum potassium concentrations at screening to values at the end of phase I 
(week 2) and phase II (week 4) of the study. However, because potassium concentrations are also being used to 
titrate the dose of patiromer needed to achieve normal potassium concentrations, fasting serum potassium 
concentrations will also be measured at the end of weeks 1 and 3. To ensure a rapid response to changes in 
serum potassium concentrations, blood samples obtained at the CTSI CRC will be immediately delivered to the 
study laboratory at Tisch Hospital for analysis, and the results sent to the CTSI Pharmacy for evaluation 
(section 10.a.i.). Participants will be directed to pick up new prescriptions from the CTSI Pharmacy on the days 
of measurement. To obtain a measurement of serum potassium concentration, a 0.5 mL sample of blood is 
required. 
iv. Blood pressure. Systolic and diastolic blood pressures will be measured after 5-minutes of rest in a 
seated position with their arm supported at the level of their heart and their feet resting of the floor using an 
automatic sphygmomanometer. Blood pressure measurements will be obtained in duplicate with a third measure 
obtained if the systolic or diastolic values on repeated measurement differ by more than 5 mmHg.  


Protocol Version 6 – 07.10.2019 
v. Gastrointestinal symptoms. The frequency and severity of participant gastrointestinal symptoms in the 
previous week (abdominal cramping, abdominal discomfort, indigestion, infrequent or difficult to pass bowel 
movements, flatulence, loose or watery stools) will be self-reported via an investigator-developed questionnaire 
at baseline, and at the end of the stabilization period (week 1), phase I diet (week 2), and phase II diet (week 4).  
vi. Other biochemical parameters. Fasting blood samples will be obtained at the CTSI CRC, and analyzed 
for concentrations of phosphorus, calcium, magnesium, albumin, glucose, insulin, cholesterol, LDL-cholesterol, 
HDL-cholesterol, triglycerides, urea nitrogen, bicarbonate and C-reactive protein. Similar to serum potassium 
concentrations, blood samples will be delivered by study staff to the laboratory at Tisch Hospital for analysis. 
To obtain these biochemical measurements, approximately 5.0 mL of blood is required.  
 
Table 4. Summary of study visits and procedures 
 
Screening Baseline Wk 1 Wk 2 
Wk 3 
Wk 4 
Baseline Questionnaire (comorbidities, 
sociodemographics, tobacco and alcohol use, use of 
dietary supplements and urine output) 
 
X 
 
 
 
 
Medical Chart Review (cause of CKD, 
comorbidities, urine albumin concentration) 
 
X 
 
 
 
 
Medical Chart Review (medications) 
 
X 
 
X 
 
X 
Dietary Assessment (3-day food record) 
 
 
X 
 
 
 
Anthropometrics (height) 
X 
 
 
 
 
 
Anthropometrics (weight) 
X 
 
 
X 
 
X 
Fasting Blood Test (potassium) 
X 
 
X 
X 
X 
X 
Fasting Blood Test (phosphorus, calcium, 
magnesium, albumin, glucose, insulin, cholesterol, 
LDL-cholesterol, HDL-cholesterol, triglycerides, 
urea nitrogen, bicarbonate and C-reactive protein) 
 
X 
 
X 
 
X 
Blood Pressure (systolic and diastolic blood 
pressure) 
 
X 
 
X 
 
X 
Gastrointestinal Symptoms Questionnaire 
(frequency and severity of abdominal cramping, 
abdominal discomfort, indigestion, infrequent or 
difficult to pass bowel movements, flatulence, loose 
or watery stools in previous week) 
 
X 
X 
X 
 
X 
 
10) Data and Specimen Banking 
No samples will be stored for future analyses in this study. 
 
11) Data Management 
Information to be obtained from participants includes height and weight, blood pressure, medical history, blood 
tests, and self-administered questionnaires (sociodemographics, clinical and comorbid conditions/ management, 
cigarette and alcohol use and gastrointestinal symptoms). None of the data to be collected is considered 
sensitive in nature. Some of the participant data such as laboratory results will be linked to the participant’s 
name. Other data (e.g., height, weight, blood pressure, medical history, and surveys) will be linked to the 
participant through a subject ID number. As a further measure to protect participants’ privacy, different subject 
ID numbers will be used for study measurements and for coordinating the feeding component of the study. We 
will maintain separate files for identified and de-identified data in locked file cabinets in a locked office. Access 
to these data will be restricted to the PI (Goldfarb), and study staff responsible for gathering data and 
maintaining research files. Data will be entered into a centralized database maintained on a secure server. Data 


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in these files will be linked to participants only through their ID number – this file will be maintained in a 
locked filing cabinet at 180 Madison Avenue. All data collected will be used expressly for the purpose of the 
proposed study. 
a. Overview. 
A descriptive analysis of all data collected will be performed using appropriate graphical and numerical 
exploratory data techniques. The information obtained from this preliminary investigation of the data will be 
used to: (1) assess data quality and completeness, (2) describe univariate distributions at baseline and follow up, 
and (3) create summary statistical data for outcome variables at each time point, including the proportion of 
participants with hyperkalemia. We will identify features of the data that may necessitate special analytic 
methods (e.g., excess zeros, missing data, departures from distributional assumptions, outliers).  
For analytic analyses, we will examine: (1) changes in outcome variables (blood pressure, gastrointestinal 
symptoms, and fasting concentrations of potassium, phosphorus, calcium, magnesium, albumin, glucose, 
insulin, cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, urea nitrogen, bicarbonate and C-reactive 
protein), and covariates (weight, medications, dose of Patiromer) between baseline and the end of each diet 
phase, and (2) relationships between the changes in outcome variables and covariates. Changes in study 
outcomes will be will be graphically depicted using means + SD or median (IQR) as measures of central 
tendency and variance. Changes in study outcomes will be analyzed using repeated-measures analysis of 
variance with post-hoc Tukey HSD test. Because of the small sample size, covariates will be reported instead of 
being included in a multivariable model. Depending on the types of covariate and outcome of interest, subgroup 
analyses may be performed with these participants removed from the dataset. For example, if a participant’s 
dose of phosphorus binder medications changed during the study, the analysis of phosphorus concentrations 
would be conducted with/without this participant. Given the short during of this study (4 weeks) in relation to 
typical monitoring of patients with stage 3B-4 CKD, we expect that that few, if any, subgroup analyses will be 
required.  
 
12) Provisions to Monitor the Data to Ensure the Safety of Subjects 
Protection against Risk.  
Once half of the participants are enrolled and accrued, the PI (Goldfarb) will review serum potassium 
concentrations to ascertain if there were any episodes of moderate-severe hyperkalemia, or protocol issues that 
require reporting, withdrawing a participant and/or stopping the study. An AE is any unfavorable and 
unintended sign, symptom, or disease, including worsening of pre-existing medical conditions. The criteria for 
withdrawing participants are outlined in section 14 below. The study will be stopped if there is a serious adverse 
events (SAE) related to the study. Any SAE related to the intervention will be reported to the NYU School of 
Medicine Institutional Review Board by phone and email within 24-hours of being notified. To minimize 
participant risk and facilitate monitoring, we plan to enroll cohorts of ≤2 participants rather than a single cohort 
of 10 participants. Summary data and safety monitoring reports will be submitted to the NYU School of 
Medicine Institutional Review Board during annual review, or if there are changes in the risk/benefit ratio of the 
study. 
As per our Clinical Trial Agreement with Relypsa, Inc., the PI will undergo training in reporting AEs by 
Relypsa, Inc. before starting the study, and will report all AEs that occur after the signing of informed consent, 
and up to 14 days after the intervention to the Drug Safety and Pharmacovigilance (DSPV) Department at 
Relypsa, Inc within 15 days of completing the study. Any AEs that are considered serious (SAEs), which occur 
will be reported to Relypsa, Inc. DSPV Department within 24-hours of being identified/reported. SAE include 
“any untoward medical occurrence that at any dose: (i) results in death; (ii) is immediately life threatening (i.e. 
in the opinion of the investigator, the AE places the subject at immediate risk of death; it does not include a 
reaction that, had it occurred in a more severe form, might have caused death); (iii) requires inpatient 


Protocol Version 6 – 07.10.2019 
hospitalization or results in prolongation of an existing hospitalization; (iv) results in a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions; (v) is a congenital anomaly or 
birth defect; or (vi) is an important medical event that may not be immediately life threatening, result in death, 
or require hospitalization, but may be considered an SAE when, based upon appropriate medical judgment, it 
jeopardizes the subject or may require medical or surgical intervention to prevent one of the outcomes listed in 
subsections (i) – (v)” (defined per the Clinical Trial Agreement with Relypsa, Inc.).  
This study investigates the use of patiromer for managing normal serum potassium concentrations in CKD 
patients who are transitioned to a plant-rich diet. The major risk to participants in this study is cardiotoxicity 
related to hyperkalemia. Patiromer has been demonstrated to be effective for lowering serum potassium 
concentrations and keeping them in the normal range in CKD patients with hyperkalemia, but the role of dietary 
potassium on serum potassium concentrations is unclear. Current dietary guidelines for managing hyperkalemia 
in CKD patients recommend avoiding high-potassium plant foods; however, this long-standing practice has 
never been demonstrated to be necessary, and may contribute to other disease complications4. To our 
knowledge, this is the first study to evaluate liberalizing the diets of CKD patients with hyperkalemia, so we 
have incorporated many design features that can help us to protect against this risk. 
Prior to the intervention, participants will receive education on the signs and symptoms of hyperkalemia; 
muscle weakness, abnormally slow or rapid heart rate, and heart palpitations (from Patient education: 
Hyperkalemia (the basics); UpToDate.com)6. Participants will be directed to monitor themselves for these 
conditions, and to go to the emergency room if they start experiencing them, making sure to notify the 
emergency department staff about their participation in the study. Standard treatment for acute episodes of 
hyperkalemia includes intravenous infusions of calcium gluconate and glucose/insulin, often followed by 
polystyrene sulfonate or emergent dialysis to remove excess potassium. The emergent treatment of adverse 
events will be at the discretion of the attending physician. In the event of any admission to the emergency room 
(even if determined to be unrelated to hyperkalemia), participants will be asked to alert the study PIs as soon as 
possible.   
The intervention contains several features to lower the risk of hyperkalemia. For one, the research diets will 
be prepared for participants to provide control over the dietary potassium exposure. We will use the feeding 
study approach that gradually increases dietary potassium in a step-wise manner in order to prevent large shifts 
in dietary potassium intake. During phase I, participants will be stabilized on a plant-rich diet that restricts dairy 
products and excludes fruits and vegetables that are high in potassium. This closely approximates the current 
dietary recommendations for CKD patients with hyperkalemia, but does include plant-based foods from the 
Protein Foods Group (legumes, nuts, seeds), which are high in potassium (>200 mg/serving). However, 
compared to the typical Western diet, plant-rich diets are more alkaline, and are higher in fiber, factors that are 
thought to help control serum potassium concentrations4. After a week of consuming this diet, high-potassium 
fruits and vegetables will be introduced, and make up half of the fruit and vegetable servings. We will closely 
monitor participants’ adherence to the research diets through daily food records to ascertain their adherence 
with the study diets – participants that are determined to be non-adherent with the research diets at the end of 
phase I (defined in section 14) will be withdrawn from the study.   
Another intervention feature to lower the risk of hyperkalemia is the close monitoring of participants’ serum 
potassium concentrations to adjust the dose of patiromer (10.a.i. Table 2). We will measure serum potassium 
concentrations as per current patiromer recommendations (weekly), and samples will be processed through the 
Tisch Laboratory, and the results sent to the CTSI Pharmacy for review. If values are abnormally high or 
rapidly increasing towards hyperkalemia (10.a.i. Table 2), the study nephrologist (D.S.G.) will be immediately 
contacted. Because hemolysis can cause artificially elevated serum potassium values, participants with 
abnormally high or rapidly increasing concentrations of serum potassium will have another blood test to 
confirm their serum potassium concentrations.  


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In addition to risks associated with hyperkalemia, there are potential risks related with patiromer use. In a 
sample of 734 patients treated with patiromer, the most common AEs were constipation (7.2%), 
hypomagnesemia (5.3%), diarrhea (4.8%), nausea (4.8%), abdominal discomfort (2.0%) and flatulence (2.0%). 
It is likely that the most common of these AEs (constipation, hypomagnesemia, diarrhea) would be attenuated 
by a plant-rich diet, which contains higher amounts of fiber and magnesium compared to the typical Western 
diet. The less common adverse events (abdominal discomfort, flatulence) may be exacerbated by the higher 
intakes of dietary fiber. These potential AEs will be assessed at the end of each week through the 
gastrointestinal symptoms questionnaire, and blood testing at the end of phase I and II (for hypomagnesemia). 
Patiromer also has the potential to bind to other medication, reducing their absorption. This will be mitigated by 
directing patients to take patiromer once daily, and at least 3 hours away from other medications.  
It is unlikely that women and men with stages 3-4 CKD will become pregnant or impregnate someone. 
Additionally, we will exclude anyone who is planning on becoming pregnant from the study. As part of our 
Clinical Trial Agreement with Relypsa, Inc., we will report any pregnancies (whether female or male 
impregnating a female) to Relypsa, Inc. In addition, because the patiromer and the research diets are untested in 
pregnant women, we will withdraw women who become pregnant during the study period.  
Lastly, participants in the study are at risk of breaches of confidentiality. A variety of measures will be used 
to prevent breaches of confidentiality. First, all study staff will be trained in the NYULMC Practice 
Fundamentals, which include training in issues of confidentiality. Additionally, all study staff will be required 
to sign a confidentiality agreement. Although study staff may have access to sensitive information about the 
participant as recorded in their medical record, only that information pertinent to the study outcomes will be 
abstracted from the medical record. Data will be maintained as described above (see section 12). We will take 
steps to avoid participants’ perceptions of coercion in the recruitment process.  
 
13)  Withdrawal of subjects  
As mentioned previously, participants may be withdrawn from the study without their consent in the event that 
they become pregnant, or they are non-adherent with the research diets. Non-adherence to the research diets will 
be defined as consumption of >25% of energy from non-research diet foods, which will be assessed at the end 
of phase I of the study. In the event that involuntary withdrawal is required, participants will be referred back to 
their treating physician of record for evaluation and management. Data collection will cease at the time of 
withdrawal.  
 
14)  Risks to subjects  
Most of the risks associated with this study are outlined in section 13 along with corresponding measures to 
protect against these risks (include hyperkalemia, patiromer side effects and interactions with medications, and 
breach of confidentiality). Blood tests will be drawn for this study, which are sometimes accompanied by 
bruising, bleeding, and minor tenderness at the puncture site. Participants will be made aware of all of these 
risks prior to enrolling in this study. 
 
15)  Potential Benefits of the Proposed Research to the Subjects and Others  
Participants may experience some temporary improvement in cardiometabolic risk factors and serum 
potassium concentrations related to intervention; however, this is not guaranteed. Moreover, any temporary 
improvements in these conditions are unlikely to have any lasting benefits to participants.  
This study will not provide the investigators with data to demonstrate improvements in health-related 
quality of life, morbidity, mortality, and utilization or cost of care. However, if proven efficacious, future CKD 
patients may benefit from the knowledge generated from this study regarding the need to limit or avoid high- 
high-potassium plant foods, and the potential health benefits of a plant-rich dietary pattern. Because this is a 


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proof-of-concept study, the emphasis has been placed on safety and internal validity rather than real-world 
applicability and generalizability to the CKD population. Consequently, this is just a first step in several needed 
to benefit future CKD patients.  Additional longer-term studies in free-living CKD patients would be needed 
before any such changes in practice could be realized.  
 
16)  Vulnerable populations  
No vulnerable populations are included in this study. 
 
17)  Multi-site research  
Not applicable. 
 
18) Community-based participatory research  
Not applicable. 
 
19)  Sharing results with subjects  
The study results will not be shared with participants who will be expected to return to usual care practices upon 
completion of the study. 
 
20) . Setting 
Research activities will occur at the CTSI CRC and Renal Clinic of the New York VA. Ethical review will be 
obtained from the Institutional Review Board at NYULMC.  
 
 
21) Resources available  
i). Personnel. 
INVESTIGATORS 
David Goldfarb, MD (Principal Investigator, Effort = 0.6 CM) is a Professor in the Departments of 
Medicine and Neuroscience and Physiology at the New York University School of Medicine, and Chief of 
Nephrology at the Renal Clinic of the New York VA. He is a nephrologist with extensive clinical and research 
experience with individuals with chronic kidney disease, including trials of medications. He is well- known in 
the local nephrology community. Dr. Goldfarb is co-investigator to Dr. Sevick’s ongoing Diabetes Healthy 
Hearts study (R01), and pending Kidneys and Behavioral Management of Phosphorus study (R21). He will 
provide crucial medical oversight to the study, in particular safety monitoring, patiromer prescriptions, and 
assist with interpretation of data from a medical perspective in the dissemination of study results. Dr. Goldfarb 
has a part-time university position and his effort is estimated as a function of his university appointment. 
Mary Ann Sevick, ScD, RN, (Co-Investigator. Effort = 0.6 CM) is a Professor in the Department of 
Population Health at New York University School of Medicine, and Director of the mHealth Unit in the Center 
for Healthful Behavior Change. Over the past 20 years, Dr. Sevick has had experience with a variety of large 
clinical trials. Her primary interest is in the area of chronic illness and she has recently been involved, as 
principal investigator, in several studies to examine disease management regimens. She recently completed the 
BalanceWise study (NIH-R01-NR010135), a randomized clinical trial to evaluate the efficacy of a behavioral 
intervention to reduce sodium intake in hemodialysis patients, and is currently the principal investigator of the 
NIDDK-funded Diabetes Healthy Hearts and Kidneys Study R01, a clinical trial evaluating alternative uses of 
technology to change multiple behaviors in those with diabetes and concurrent stage 2-4 chronic kidney disease. 
As an experienced clinical investigator in the Center for Healthful Behavior Change, Dr. Sevick will work 
closely with Dr. Goldfarb to manage the proposed project. 
Simon Jones, PhD MSc (Co-Investigator, Effort = 0.6 CM) is a Research Professor in the Department of 


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Population Health at the New York University School of Medicine at the University. Dr. Jones has extensive 
experience in data management and statistical analysis. As such, he will oversee generation of preliminary 
reports for data quality, safety, and recruitment. In addition, he will review all analyses specified in the 
proposal, and assist with interpretation of these analyses in the dissemination of study results.  
OTHER PERSONNEL  
Margaret Curran, (Research Coordinator, 0.6 CM). The research coordinator will work with staff at the 
New York Harbor VA Healthcare System and CTSI-CRC. She will be responsible for conducting screening, 
baseline and follow up measurement visits, reviewing participant’s medical charts for eligibility, obtaining 
informed consent, and coordinating study visits.  
ii). Institutional setting.  
Renal Clinic at the New York Harbor Veterans Affairs Healthcare System: The Renal Clinic at the New 
York Harbor VA Healthcare System serves approximately 250 CKD patients in the Greater New York City 
region, and will be the source population for this study. The electronic medical records system at the New York 
VA Healthcare System will be used to assist in identifying potentially eligible patients for the study, and for 
obtaining clinical information to describe the patient population. 
Department of Population Health, NYULMC: The Department of Population Health, within NYUSOM, 
aims to integrate, support, and advance NYULMC's contributions to population health research and related 
disciplines, providing a vibrant departmental home for the "bedside-to-population" as well as the "population-
to-discovery" domains of translational research. It provides an academic base for efforts to integrate research 
into NYU's expanding health care delivery system that transcends any particular school, department, or 
division. The Department is a research and training hub that brings together researchers in nursing, medicine, 
psychology, epidemiology, biostatistics, health services and policy, behavior change, comparative effectiveness, 
medical ethics, prevention, and related disciplines, affording a unique and collaborative environment focused on 
improving the health of populations. The Department was initiated in January 2012. A core focus of the 
Department is improving health outcomes through innovative interventions as well as in enhancing the impact 
of interventions already known to be effective through their more effective implementation and dissemination. 
Collaboration with key public sector stakeholders and with community partners is central to the Department’s 
mission. As researchers, faculty are engaged in dual roles: building cutting-edge science in their areas of 
inquiry, and providing collaborative consultation to other investigators throughout the NYULMC academic 
community as well as across the University. Resources within the Department for this proposal include the use 
of over 5,000 square feet of dedicated office space located on the newly renovated 6th floor of the NYULMC 
Translational Research Building, telecom (phone, fax and LAN connections), administrative assistants, and 
grant, regulatory (IRB) and finance administrators.  
Center for Healthful Behavior Change, NYULMC: The Center for Healthful Behavior Change (CHBC) is 
located within the Department of Population Health. The mission of CHBC is to become a national leader in 
translational behavioral medicine, research, training, and education. The CHBC works toward this mission 
through the development, implementation, and dissemination of innovative evidence-based behavioral 
interventions in routine clinical practice and community-based settings with the long-term goal of disseminating 
effective strategies nationally and internationally. The Center is comprised of core research faculty members 
with expertise in various fields relevant to translational behavioral research. Faculty engage in research 
pertaining to heart disease, hypertension, chronic kidney disease, diabetes, cancer, health disparities research, 
community-based participatory research, health psychology, behavioral informatics, and health education and 
counseling.  
Division of Biostatistics NYULMC: Dr. Jones’ office is 180 Madison Avenue, in the same building as the 
study coordinator (M.C.). Dr. Jones has access to state-of-the-art computing facilities that include a central 
server (Dell PowerEdge 2500) and a Sun Server. Statistical software available either on the network or the 


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desktop includes SAS, SPSS, S-Plus (including Spatial Stats and Environmental Statistics Modules), R, PASS 
and Matlab.  
Portable Chef: Portable Chef is a metabolic kitchen / foodservice vender that will carry out the critical task of 
preparing meals and snacks for the study. This responsibility includes developing menus based on the pre-
defined dietary patterns, sourcing ingredients, preparing and weighing foods and beverages, and delivering them 
to the participants to consume. The project study dietitian (D.E.S.) reviewed available foodservice operations in 
the Greater New York City area, and selected Portable Chef for this intervention based on their capacity, 
delivery, and experience in developing and preparing tailored, weighed menus for researchers and clients with 
special food requirements.  
 
22)  Prior approvals 
We have received approval from the Chief of the Nephrology at the New York Harbor VA Healthcare System 
to coordinate this study in their Renal Clinic. We also have approval from Portable Chef Director (Uri Attia), 
and a vendor agreement with Portable Chef is already in place for prior research projects. 
 
23)  Subject Payments 
Potential participants will be paid $25.00 for the screening visit, and enrolled participants will additionally 
receive $25.00 per visit to the CTSI CRC.  
 
24) Local number of subjects 
We will recruit a total of 10 individuals to the study. Preliminary data from the New York Harbor VA 
Healthcare System indicate that we will have access to approximately 250 patients with CKD, ~10% of which 
have hyperkalemia.  
 
25) Confidentiality 
Some of the participant data such as laboratory results will be linked to the participant’s name in their medical 
chart. Other data (e.g., surveys) will be linked to the participant through an ID number. We will maintain 
separate files for identified and de-identified data in locked file cabinets in a locked office. Access to these data 
will be restricted to the PI (Goldfarb), and study staff responsible for gathering data and maintaining research 
files. Data will be entered into a centralized database maintained on a secure server. Data in these files will be 
linked to participants only through their ID number. All data collected will be used expressly for the purpose of 
the proposed study.  
 
26) Provisions to Protect the Privacy Interests of Subjects 
Measures to be used to protect subjects’ privacy interests are described in section 13 above. Data collection will 
occur at the New York Harbor VA Healthcare System (for medical chart review), CTSI Pharmacy (for 
patiromer dose), and CTSI CRC (questionnaires, anthropometric and clinical measurements, blood tests). 
Measurements at the CTSI will be conducted in private rooms. Participants will be told that they can refuse to 
respond to any questions that make them uncomfortable, and that they can withdraw from the study at any time. 
 
27) Compensation for research-related injury  
Participants will not be compensated for research-related injuries. 
 
28) Economic burden to subjects 
Neither the patient nor the patient’s health insurance will be billed for any study activities (including research 
diets), tests, or procedures related to the study. The cost of all procedures and tests will be covered by funds 


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received from Relypsa, Inc.  
 
29) Consent process 
A brief description of the study will be provided at the time of screening for the study. After reviewing the 
consent form with patients, and after they have signed the consent form, we will verify that they meet the 
inclusion/exclusion criteria (sections 5.i and 5.ii.). Potential participants will be shown the research diet menus 
to determine whether they are willing and able to adhere to the research diets. All questions will be answered. 
A copy of the consent form will be given to the participant and they will be encouraged to contact the 
PIs with any and all questions that occur at any time during the conduct of the study. No patients will be 
excluded on the basis of race/ethnicity, but this pilot study has a sample size that is insufficient to examine 
differences in the intervention by race/ethnicity.  
 
30) Process to document consent in writing 
Patient’s consented participation in this study will be documented in their medical record.  
 
31) Drugs or devices 
Participants in this study will be prescribed patiromer (dosing 10.a.i. Table 2), under the supervision of the 
study nephrologist (D.S.G.). Patiromer is an FDA-approved cation-exchange polymer that binds to potassium in 
the digestive tract, and is excreted (along with bound potassium) in feces. Patiromer is indicated for the 
treatment of hyperkalemia, and is demonstrated to result in clinically significant reductions in serum potassium 
concentrations. The safety concerns associated with patiromer, along with measures to reduce these 
complications, are noted in section 13, and include constipation (7.2%), hypomagnesemia (5.3%), diarrhea 
(4.8%), nausea (4.8%), abdominal discomfort (2.0%) and flatulence (2.0%), and binding to other medications.   
 
References. 
 
1. United States Renal Data System. 2016 USRDS annual data report: Epidemiology of kidney disease 
in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and 
Kidney Diseases, Bethesda, MD, 2016. 
2. Einhorn LM, Zhan M, Hsu VD, Walker LD, Moen MF, Seliger SL, Weir MR, Fink J. The frequency of 
hyperkalemia and its significance in chronic kidney disease. Arch Intern Med 2009;169(12):1156-
1162. 
3. Takaichi K, Takemoto F, Ubara Y, Mori Y. Analysis of factors causing hyperkalemia. Intern Med 
2007;46(12):823-829. 
4. St-Jules DE, Goldfarb DS, Sevick MA. Nutrient non-equivalence: Does restricting high-potassium plant 
foods help to prevent hyperkalemia in hemodialysis patients? J Ren Nutr 2016;26(5):282-287. 
5. Wier MR, Bakris GL, Bushinsky DA, Mayo MR, Garza D, Stasiv Y, et al. for the OPAL-HK Investigators. 
Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med 
2015;372(3):211-221. 
6. UpToDate®. Patient education: Hyperkalemia (the basics). UpToDate website. 
https://www.uptodate.com/contents/hyperkalemia-the-basics?source=see_link. Accessed February 
20, 2017.