The Effects of Patiromer on Serum Potassium Level and Gut Microbiome of ESRD Patients With Hyperkalemia

Study Overview
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Brief Summary
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The Effects of Patiromer on Serum Potassium Level and Gut Microbiome of ESRD Patients With Hyperkalemia (potassium greater than 5 milliequivalents per liter) is a non-randomized, crossover study. This is an open-label, pilot clinical trial with 3 sequential phases of (a) 2 weeks of no intervention, (b) 12 weeks of Patiromer treatment, and (c) 6 weeks of no intervention. Treatment with Patiromer will be initiated at a dose of 8.4 grams, once daily and observed for a week, then uptitrated to 16.8 grams once daily. Eligible study subjects will collect stool samples and provide blood and urine samples.

Official Title
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The Effects of Patiromer on Serum Potassium Level and Gut Microbiome of End Stage Renal Disease Patients With Hyperkalemia

Conditions
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ESRD, Hyperkalemia, End Stage Renal Disease

Intervention / Treatment
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* Drug: Patiromer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects on stable hemodialysis for more than 90 days. Age 18-85 years. Persistent hyperkalemia, defined as elevated serum potassium > 5.0 mEq/L in more than 2 occasions during the previous 3 months. Exclusion Criteria: Use of pre- or probiotics during the past 2 months Use of antibiotics within the past 2 months, if the patient received a single course of antibiotic. Presence of chronic wound infection and osteomyelitis Inflammatory bowel disease, chronic diarrhea, current C. difficile infection Liver cirrhosis or chronic active hepatitis Treatment with immunosuppressive medications in the past 6 months or more than a week of treatment with prednisone > 10 mg in the last 3 months Anticipated kidney transplant within 9 months Expected survival < 9 months Pregnancy, anticipated pregnancy, or breastfeeding Incarceration Participation in another intervention study severe anemia defined as hemoglobin < 8.0 g/dl any time during the last 2 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patiromer<br>This arm is a 2 week observation period before the start of the Patiromer treatment phase, followed by a 12 week treatment phase, and 6 week no treatment observation phase. Pre-Treatment (Wk 1-2): Observational period. Baseline sample collection of blood and stool. No medication. Treatment (Wk 3-14): Participants will take 8.4 grams of Patiromer once daily for one week, during which serum potassium and gastrointestinal symptoms will be evaluated. If tolerated and in the absence of hypokalemia, the dose will be up-titrated to 16.8 grams once daily for the remaining 11 weeks. Blood and stool will be collected. Post-Treatment (Wk 15-20): Observational period. No medication. Blood and stool will be collected. | Drug: Patiromer<br>* Patiromer will be orally self-administered by participants.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events of Participants Taking Patiromer in Lowering Serum Potassium Levels in End Stage Renal Disease (ESRD) Patients With Hyperkalemia Measured by Gastrointestinal Symptom Rating Scale (GSRS) | The Gastrointestinal Symptom Rating Scale was used to measures any potential side effects due to study medication. Survey was administered at Wk 1, Wk 8, Wk 14, and Wk 20. For symptoms (abdomen pain - diarrhea) a score of 0 indicates no discomfort, 1 = mild discomfort, 2=moderate, 3=severe; higher score means a worse outcome For stool form, 1=Well formed, 2=Semi formed, 3= Loose, 4= Liquid;higher score means a worse outcome For number of stools per day, 1= <1, 2=1 or 2, 3=3 or 4, 4=5 or 6,5= 7 or more; higher score means a worse outcome | Wk 2 (Pre-Treatment), Wk 14 (Treatment), Wk 20 (Post-Treatment) | 
| Serum Potassium Level Through 12 Weeks of Treatment | Blood was collected during Pre-Treatment week 2, Treatment Week 14, and Post-Treatment week 20 | Wk 2 (Pre-Treatment), Wk 14 (Treatment), Wk 20 (Post-Treatment) | 
| Changes in Blood Chemistry During the Study |  | Wk 2 (Pre-Treatment), Wk 14 (Treatment), Wk 20 (Post-Treatment) | 
| Stool Electrolytes During the Study Phases |  | Wk 2 (Pre-Treatment), Wk 14 (Treatment), Wk 20 (Post-Treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Plasma Metabolites Using p-Cresol of Hyperkalemic ESRD Patients Treated With Patiromer | Blood and stool samples collected from the ESRD patient will be collected at pre-specified time points and analyzed by untargeted and targeted metabolomics for stool and serum metabolome profiles. | Wk 2 (Pre-Treatment), Wk 14 (Treatment), Wk 20 (Post-Treatment) | 
| Changes in Gut Microbiome of Hyperkalemic ESRD Patients Treated With Patiromer. | Blood and stool samples collected from the ESRD patient will be collected at pre-specified time points and analyzed by metagenomics for gut microbiome profile. | Wk 2 (Pre-Treatment), Wk 14 (Treatment), Wk 20 (Post-treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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End Stage Renal Disease, ESRD, Hyperkalemia