Effects of Whole Food, Plant-Based Nutrition on Chronic Kidney Disease With Proteinuria

Study Overview
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Brief Summary
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This study will test the hypothesis that lifestyle intervention consisting of a whole food, plant-based (WFPB) diet and group education will favorably impact outcomes germane to individuals with chronic kidney disease (CKD) stage 3b and 4, including blood pressure control, amount of proteinuria (protein in the urine), and preservation of glomerular filtration rate (GFR). In addition, this study will assess weight and body composition, diabetic control in subjects with diabetes as well as CKD, and quality of life. Safety of a WFPB diet in subjects with CKD will be tested with respect to the development of elevated serum potassium and phosphorus, hypoalbuminemia (low blood protein), hypotension (low blood pressure), and hypoglycemia (low blood sugar). An exploratory aim is to test the effects of a WFPB diet on the microbiome of subjects by collecting and analyzing stool samples.

Official Title
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Effects of a Whole Food, Plant-Based Nutrition Program on Subjects With Chronic Kidney Disease and Proteinuria

Conditions
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Proteinuria, Chronic Kidney Disease Stage 3B, Chronic Kidney Disease, Stage 4

Intervention / Treatment
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* Other: whole food, plant-based diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 18 years Subjects with CKD 3b and 4 (as determined by an estimated glomerular filtration rate of ≥ 15 ml/min but ≤ 45 ml/min for at least three months) Subjects with proteinuria documented at least twice with the most recent test within the last 6 months as determined by: Urine albumin excretion rate of > 300 mg/day or urine albumin to creatinine ratio of > 300 mg/g of creatinine Urine protein excretion rate of > 500 mg/day or urine protein to creatinine ratio of > 0.5 g/g of creatinine If using angiotensin converting enzyme inhibitor, angiotensin receptor blockers and/or aldosterone antagonists, on a stable dose of for greater than one month Fluent in English language Able and willing to comply with the testing and group education schedules Able and willing to comply with a whole-food, plant-based diet Able and willing to give informed consent Exclusion Criteria: Any kidney disease requiring immunosuppressive therapy Pregnancy or intent to become pregnant in the next 12 months Life expectancy < 12 months History of solid organ transplant or anticipated solid organ transplant in next 12 months History of hyperkalemia: Two potassium measurements > 5.1 Meq/L within the last three months, or history of any intervention for hyperkalemia in the last 6 months Subjects with malabsorptive syndromes Subjects with history of bariatric surgery or planned bariatric surgery in the next 12 months Subjects on warfarin Subjects with current eating disorders Subjects with tobacco or illicit substance use Subjects with alcohol use of > 7 drinks per week Allergy or intolerance of a plant-based or plant-derived food (gluten, soy, etc.) Following a vegan diet in the six months prior to consent Major surgery within 60 days prior to consent

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The initial phase of the study will be a three month randomized clinical trial of a whole food plant based nutrition program vs. usual care in patients with chronic kidney disease. Subjects randomized to the intervention arm will start the nutrition program as soon as they are able. Subjects assigned to the control arm will be placed on a 'wait-list' to start the nutrition program after they undergo three months of testing during their usual care, which consists of routine CKD care as directed by their primary nephrologist. After a 3 month 'wait', they will start the same plant-based nutrition program as the intervention arm subjects. Both experimental and control group subjects will be followed for a total of 9 months after starting the plant-based dietary intervention. Thus, in addition to the 3-month randomized control trial, there will be data from a 9-month single arm clinical intervention.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Subjects in this arm will immediately begin a whole-food, plant-based nutrition program consisting of weekly educational group meetings and prepared meals delivered to the subjects' homes for the first 12 weeks followed by monthly educational group meetings for an additional 6 months. | Other: whole food, plant-based diet<br>* The study diet is whole food, plant based defined as containing no animal products or refined grains or added oils, minimal use of any sweeteners, and, for the purposes of this study, on average containing no more than 15% calories from fat.<br>|
| Other: Wait List Control<br>Subjects in this arm will continue their usual care as directed by their nephrologist for 12 weeks before starting the same whole-food, plant-based nutrition program as the intervention arm subjects. | Other: whole food, plant-based diet<br>* The study diet is whole food, plant based defined as containing no animal products or refined grains or added oils, minimal use of any sweeteners, and, for the purposes of this study, on average containing no more than 15% calories from fat.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in systolic and diastolic blood pressure from baseline |  | 4, 8, and 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| Change in proteinuria from baseline | Urine total protein:creatinine ratio | 4, 8, and 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| Change in GFR from baseline | Serum creatinine (renal function panel) and Cystatin C | 1, 4, 8, and 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight changes from baseline |  | 4, 8, and 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| BMI changes from baseline |  | 4, 8, and 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| Waist circumference changes from baseline |  | 4, 8, and 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| 8-point bioelectrical impedance analysis changes from baseline | Body composition assessment | 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| Hemoglobin A1c changes from baseline | Diabetic control | 4, 8, and 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| KDQOL-36 changes from baseline | Scoring of this questionnaire consists of 5 scales (symptoms/problem list, effects of kidney disease, burden of kidney disease, SF-12 physical composite, and SF-12 mental composite). The lowest possible score for each scale is 0, indicating the worst outcome, and the best possible score is 100, indicating the best possible outcome. | 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| Serum potassium changes from baseline |  | 1, 4, 8, and 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| Serum phosphorus changes from baseline |  | 1, 4, 8, and 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| Serum albumin changes from baseline |  | 1, 4, 8, and 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| Blood glucose level changes from baseline | Fasting serum levels from all subjects; additionally, whole blood levels measured by glucometer in subjects with comorbid type 1 or type 2 diabetes mellitus | 1, 4, 8, and 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| Total cholesterol, HDL, LDL, and non-HDL cholesterol level changes from baseline | Fasting lipid panel | 1, 4, and 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| Serum magnesium changes from baseline |  | 1, 4, 8, and 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| Parathyroid hormone (PTH) changes from baseline |  | 12 weeks (RCT); 3 and 9 months on intervention diet (all subjects) | 
| 25-hydroxycholecalciferol changes from baseline |  | 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| Fibroblast growth factor-23 changes from baseline |  | 12 weeks (RCT); 3 and 9 months on intervention diet (all subjects) | 
| High sensitivity CRP changes from baseline |  | 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| CBC with differential changes from baseline |  | 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| Changes in nutrient intakes from baseline based on 3 day food diaries | Assess baseline compared to intervention diet and assess compliance of intervention diet over study duration | 12 weeks (RCT); 3, 6, and 9 months on intervention diet (all subjects) | 
| Changes in urinary indicators of dietary intake from baseline | 24 hour urine collection, urinary oxidation (urinary 8-isoprostane) | 12 weeks (RCT); 3 and 9 months on intervention diet (all subjects) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CKD, proteinuria, diet, plant-based diet, vegan, randomized controlled trial