Clinical trial NCT05514184: Plant-Focused Nutrition in Patients With Diabetes and Chronic Kidney Disease
Official title: Plant-Focused Nutrition in Patients With Diabetes and Chronic Kidney Disease (PLAFOND Study): A Pilot/Feasibility Study
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Chronic Kidney Disease (CKD) With Diabetes Mellitus (DM)
CKD Stage 3
CKD Stage 4
CKD Stage 5
Diabetes Mellitus
Diabetic Kidney Disease
Keywords: plant-dominant low protein (PLADO) diet
plant-focused nutrition in CKD/DM (PLAFOND) diet
plant-based protein
glomerular hyperfiltration
high-protein diet
potassium restricted diet
renal disease progression
pilot/feasibility randomized controlled trial
diet adherence
meal plans
renal diet
Veterans
animal protein
continuous glucose monitoring (CGM)
CKD-related symptoms
24-hour urine nitrogen
Cystatin C and associated eGFR
dietary education
Medical Nutrition Therapy (MNT)
uremic symptoms
Lead sponsor: University of California, Irvine
Sponsor class: OTHER
Collaborators: name: VA Long Beach Healthcare System
First posted: 2022-08-24
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a pilot/feasibility, two-center (UCI and VA Long Beach), unblinded, randomized controlled trial, conducted in parallel with patients' routine CKD clinic visits, to test feasibility and safety of a patient-centered Plant-Focused Nutrition in CKD/DM (PLAFOND) comprised of \>2/3 plant proteins compared to the standard-of-care renal diet, i.e., low K content with \<1/3 plant protein.
Primary purpose: TREATMENT

Brief summary: In this pilot clinical trial, the investigators will recruit and randomize 120 patients with diabetes mellitus and chronic kidney disease (CKD/DM) stages 3 to 5 to a patient-centered and flexible Plant-Focused Nutrition in Diabetes (PLAFOND) diet with \>2/3 plant-based sources, which will be compared with a standard-of-care CKD diet, which is usually a low-potassium and low-salt diet, over a 6-month period. Through this study, the investigators will determine whether the plant-focused diet intervention is feasible for patient adherence, whether this diet is safe by avoiding malnutrition, frailty, and high potassium or glucose blood levels, and whether patient reported outcomes are favorably impacted.

Detailed description: Chronic kidney disease (CKD) affects 10-15% of US adults including 30-40% of persons with diabetes mellitus (DM), is associated with poor outcomes, and often progresses to requiring dialysis or transplantation. Half of all Americans with CKD also have DM. While traditional and emerging pharmacotherapies are often used in CKD with diabetes (CKD/DM), the synergistic role of dietary interventions has not been well examined. Low-carbohydrate low-fat diets are often recommended in DM, whereas low-protein diets (LPDs) are recommended for non-diabetic CKD with increasing emphasis on plant-based protein sources. Evidence suggests that high-protein diets with greater animal protein content may lead to glomerular hyperfiltration and faster decline in renal function in patients with CKD/DM. There remains major controversy regarding the potential risks vs. benefits of plant-based diets in CKD/DM, for which guidelines remain based on expert opinion. Given conventional dietary restrictions for the management of DM, there is concern that plant-based LPDs may lead to protein-energy wasting and hyperkalemia, whereas these diets may indeed be most beneficial in patients with CKD/DM given their faster rates of CKD progression as compared to non-diabetics. At present, clinical practice guidelines provide conflicting recommendations regarding the amount (low vs. high) and source (plant vs. animal) of dietary protein intake (DPI) in CKD/DM. Given that prior dietary trials in CKD such as the 1994 Modification of Diet in Renal Disease (MDRD) study excluded CKD/DM and did not examine the optimal proportion of plant vs. animal-based proteins, there is urgent unmet need for a rigorous dietary intervention study to examine the efficacy and safety of patient-centered plant-based diets in CKD/DM.

The investigators will conduct a pilot feasibility randomized controlled trial in parallel with patients' routine follow-up visits at ambulatory clinics to test the feasibility and safety of implementing a Plant- Focused Nutrition in CKD/DM (PLAFOND) diet with a DPI of 0.6-0.8 g/kg/d comprised of \>2/3 plant-based sources, vs. standard-of-care renal diet with \<1/3 plant-sources and low-potassium content, administrated by dietitians, over a 6-month period in 120 patients with CKD/DM stage 3-5. The investigators will determine whether the PLAFOND diet vs. the standard-of-care renal diet can be adhered to with consistent separation in dietary protein and plant-based proportions at 3- and 6-months. The investigators will also examine nutritional status, physical performance, and body composition, as well as glycemic measures using traditional metrics and continuous glucose monitoring, while other biochemical parameters and patient-reported outcomes including CKD-related symptoms will also be studied. In addition to providing the requisite feasibility and safety data of patient-conduct of future multi-center trials, this study will have major immediate impact by reinvigorating the critical role of dietary management of CKD/DM.

Eligibility criteria: Inclusion Criteria:

* Adult outpatient (\>18 years old) with diabetes mellitus (DM), who attends ambulatory clinics in one of the two centers, who has the established diagnosis of stage 3-5 CKD and DM regardless of degree of proteinuria, and who wishes to prevent or delay dialysis initiation, is qualified, as long as there are at least 2 eGFRs \<60 ml/min/1.73m2 three months apart with no intervening higher eGFR values.
* Participants will agree to follow the dietary instructions based on the randomization assignment and attend baseline visits as well as three additional ambulatory visits on Month 1, 3 and 6 post-randomization in person or via telehealth and respond to monthly or more frequent phone calls.

Exclusion Criteria:

* Having a terminal illness with a life expectancy \<6 months such as stage 4 metastatic cancer.
* Patients with any serum potassium \>5.5 mEq/L during the 6 months preceding the screening visit.

Primary outcomes:
measure: Dietary adherence to PLAFOND vs. standard-of-care renal diet assessed by diet diaries
timeFrame: 6 months
Secondary outcomes:
measure: Dietary adherence to PLAFOND vs. standard-of-care low-potassium renal diet assessed by 24-hour urine collections
timeFrame: 6 months
measure: Physical function measured by Short Physical Performance Battery (SPPB)
timeFrame: 6 months
measure: Physical function measured by Fried Frailty Index
timeFrame: 6 months
measure: Muscle strength measured by handgrip strength
timeFrame: 6 months
measure: Body composition using caliper anthropometry to measure mid-arm muscle circumference (MAMC)
timeFrame: 6 months
measure: Body composition using near-infrared interactance
timeFrame: 6 months
measure: Biochemical parameter: serum A1c
timeFrame: 6 months
measure: Biochemical parameter: serum potassium
timeFrame: 6 months
measure: Biochemical parameter: serum Cystatin C
timeFrame: 6 months
measure: Biochemical parameter: urinary albumin to creatinine ratio (ACR)
timeFrame: 6 months
measure: Glycemic status by continuous glucose monitoring (GCM)
timeFrame: 6 months
Other outcomes:
Locations:
city: Orange
country: United States
facility: UCI
state: California
city: Torrance
country: United States
facility: Harbor-UCLA/Lundquist
state: California
Study officials:
affiliation: University of California
name: Kamyar Kalantar-Zadeh, MD, MPH, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California
name: Connie M Rhee, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kalantar-Zadeh K, Rhee CM, Joshi S, Brown-Tortorici A, Kramer HM. Medical nutrition therapy using plant-focused low-protein meal plans for management of chronic kidney disease in diabetes. Curr Opin Nephrol Hypertens. 2022 Jan 1;31(1):26-35. doi: 10.1097/MNH.0000000000000761.
citation: Kalantar-Zadeh K, Joshi S, Schlueter R, Cooke J, Brown-Tortorici A, Donnelly M, Schulman S, Lau WL, Rhee CM, Streja E, Tantisattamo E, Ferrey AJ, Hanna R, Chen JLT, Malik S, Nguyen DV, Crowley ST, Kovesdy CP. Plant-Dominant Low-Protein Diet for Conservative Management of Chronic Kidney Disease. Nutrients. 2020 Jun 29;12(7):1931. doi: 10.3390/nu12071931.
citation: Kalantar-Zadeh K, Fouque D. Nutritional Management of Chronic Kidney Disease. N Engl J Med. 2017 Nov 2;377(18):1765-1776. doi: 10.1056/NEJMra1700312. No abstract available.
citation: Kalantar-Zadeh K, Jafar TH, Nitsch D, Neuen BL, Perkovic V. Chronic kidney disease. Lancet. 2021 Aug 28;398(10302):786-802. doi: 10.1016/S0140-6736(21)00519-5. Epub 2021 Jun 24.
citation: Kistler BM, Moore LW, Benner D, Biruete A, Boaz M, Brunori G, Chen J, Drechsler C, Guebre-Egziabher F, Hensley MK, Iseki K, Kovesdy CP, Kuhlmann MK, Saxena A, Wee PT, Brown-Tortorici A, Garibotto G, Price SR, Yee-Moon Wang A, Kalantar-Zadeh K. The International Society of Renal Nutrition and Metabolism Commentary on the National Kidney Foundation and Academy of Nutrition and Dietetics KDOQI Clinical Practice Guideline for Nutrition in Chronic Kidney Disease. J Ren Nutr. 2021 Mar;31(2):116-120.e1. doi: 10.1053/j.jrn.2020.05.002. Epub 2020 Jul 29.
citation: Kalantar-Zadeh K, Mattix-Kramer HJ, Moore LW. Culinary Medicine as a Core Component of the Medical Nutrition Therapy for Kidney Health and Disease. J Ren Nutr. 2021 Jan;31(1):1-4. doi: 10.1053/j.jrn.2020.11.002. No abstract available.
citation: Rhee CM, Kalantar-Zadeh K, Moore LW. Medical Nutrition Therapy for Diabetic Kidney Disease. J Ren Nutr. 2021 May;31(3):229-232. doi: 10.1053/j.jrn.2021.03.004. No abstract available.
citation: Kalantar-Zadeh K, Saville J, Moore LW. Unleashing the Power of Renal Nutrition in Value-Based Models of Kidney Care Choices: Leveraging Dietitians' Expertise and Medical Nutrition Therapy to Delay Dialysis Initiation. J Ren Nutr. 2022 Jul;32(4):367-370. doi: 10.1053/j.jrn.2022.05.001. Epub 2022 May 16. No abstract available.