CKD: Long-term Effects of the New Nordic Renal Diet in Patients With Moderate Chronic Kidney Disease

Sponsor

Bo Feldt-Rasmussen (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04579315

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

As Chronic Kidney Disease (CKD) progresses normophosphatemia is maintained by increasing the per nephron urinary phosphorus excretion. Clinically, hyperphosphatemia is associated with high mortality, vascular calcification, endothelial dysfunction and progression of left ventricular hypertrophy. Currently the treatment of hyperphosphatemia is first being initiated in stage 5 and consists of dietetic guidance to avoid dietary phosphate and treatment with oral phosphate binders. However, studies have shown important side effects to phosphate binders in terms of progression of vascular calcifications. Therefore, it might be beneficial to start the dietetic treatment with a reduction of dietary phosphate earlier in the disease stage.

The aim of this project is to develop a New Nordic Renal Diet (NNRD) for CKD patients' stage 3-4 and to examine the long-term effects in a period of 26-weeks. NNRD has a high content of vegetable foods, less animal products and more local food items with a lesser content of phosphorus.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease(CKD) Hyperphosphatemia Blood Pressure	Other: Intervention group; NNRD group	N/A

Detailed Description

This study is a randomized controlled trial performed at Department of Nephrology Rigshospitalet, Copenhagen Denmark. Sixty patients will be randomized to either 26 weeks on the NNRD (intervention) or 26 weeks on their habitual diet (control). The patients will be randomized by blinded drawing by lot. The study participants can leave the trial at any time during the study period, without any explanation. The investigator can at any time pull a patient out of the trial, if there is concern for the patient's safety or if there is a breach in terms of following the protocol. The principal investigator is required to document and report dropouts from the study.

The project group has entered a cooperation agreement with Danish chefs. The agreement involves that a team consisting of highly talented chefs will create the recipes for the intervention. The recipes will be created in close collaboration with the principal investigator who will use her expertise within Clinical Nutrition to combine the international nutrients guidelines and culinarian experiences. Moreover, the agreement holds that they will find the raw materials needed for the recipes and deliver them weekly to the patients' homes throughout the study period in packages containing the recipes and raw materials. There will be no financial costs for the patients. The patients in the intervention group are expected to follow the recipes five days of the week during the study period. The final two days of the week, the patients must plan their own meals. However, still following the recommended guidelines upon the NNRD whole food approach delivered from the principal investigator, who is a phd.-student and also a registered clinical dietitian and MSc in clinical nutrition (Nikita Misella Hansen).

Sample size calculation and statistical analysis:

The sample size calculation is based on results from previous studies performed by this study group. Within 6 months of participating in this study we expect a decrease in eGFR to be about 1 ml/min/1.73 m2. This will have no influence on the total amount of 24-h urine phosphorus excretion (primary endpoint), as CKD progresses normophosphatemia is maintained by increasing the per nephron urinary phosphorus excretion stimulated by an increase in FGF23 and PTH leading to progressively increasing plasma levels of FGF23 and SHP the "phospho-toxicity model hypothesis" to a compensation from PTH and FGF23. In a randomized controlled study with a type-1-error risk of 0.05 (alfa, two tailed) and a power of 80% (beta) with a standard deviation of 24-h urine phosphorus excretion of 200 mg and a minimum clinical relevant difference of 300 mg the study population is estimated to 21 in each group. In case of drop-outs we will include 30 participants in each group. Therefore, total number of patients to be included in this study is 60.

Timeline for the study:

Baseline (day 0)

Written consent will be obtained, randomization will be performed, and the following data will be registered:

Patient history: Gender, age, disease history, current medical record, diagnoses
Comorbidities - e.g. cardiovascular diseases, chronic obstructive lung disease, diabetes, hyperlipidemia, hypertension
Smoking (years) and alcohol consumption (average per week)
Blood- and urine samples
DEXA-scan and Electrocardiogram (ECG)
Blood pressure
Weight, BMI, hip- and waist circumference
Questionnaires regarding quality of life
Dietary record

Day 14 The patients will be asked to deliver a 24-hour urine sample for measuring phosphorus excretion. Furthermore, blood samples will be drawn
Day 30, 60, 90, 120, 150

Every 4th week during the study period of 26 weeks (a total of 6 times) all patients will be evaluated at the Department of Nephrology, University Hospital, Copenhagen.

During these first 5 visits the following data will be gathered:

24-h urine phosphorus excretion
Blood samples
Blood pressure
Weight, hip- and waist circumference

Once a week Once every week the principal investigator will offer all the patients a telephone meeting. Duration of the phone conversation will depend on individual needs, but up to 20 minutes per patient/week despite of allocation. The content of these conversations will evolve around dietary intake and overall general condition. The principal investigator is in close collaboration with the others in the research group who are all medical doctors and will discuss any clinical problem if needed.
Day 180 (study completion)

During the last day of the study period, the patients will be asked to meet at Rigshospitalet one more time. Data as on day 30, 60, 90, 120 and 150 will be gathered, moreover the following information will be obtained:

DEXA-scan and ECG
Weight, BMI, hip- and waist circumference
Questionnaires regarding quality of life
Dietary record

Follow-up visit Three months after study completion there will be an end-of-trial visit with a 24-h urine collection and blood samples

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Two arms, one intervention group and one control groupTwo arms, one intervention group and one control group

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Long-term Effects of the New Nordic Renal Diet on Phosphorus and Lipid Homeostasis in Patients With Chronic Kidney Disease, Stages 3 and 4 - A Randomized Controlled Trial

Actual Study Start Date :

Nov 30, 2020

Anticipated Primary Completion Date :

Sep 30, 2022

Anticipated Study Completion Date :

Nov 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Intervention group, NNRD group Main principles of the interventional whole food approach are: Maximum of 850 mg phosphorous/day Protein: 0.8 g/kg/day 80% vegetable products; 20% animal products Maximum of 5-7 g NaCl/day (table salt) Fresh raw products Seasonal oriented Fish: At least once a week Vegetarian: At least once a week Wide range of fruit and vegetables Easy to follow in daily practice Rich in flavors Sufficient content of micro- and macronutrients	Other: Intervention group; NNRD group The intervention is a whole food approach, meaning that the participants in the intervention group receives all daily food elements that they should consume
No Intervention: Control group There is no intervention, patients are following their habitual diet

Arm

Intervention/Treatment

Active Comparator: Intervention group, NNRD group

Main principles of the interventional whole food approach are: Maximum of 850 mg phosphorous/day Protein: 0.8 g/kg/day 80% vegetable products; 20% animal products Maximum of 5-7 g NaCl/day (table salt) Fresh raw products Seasonal oriented Fish: At least once a week Vegetarian: At least once a week Wide range of fruit and vegetables Easy to follow in daily practice Rich in flavors Sufficient content of micro- and macronutrients

Other: Intervention group; NNRD group

The intervention is a whole food approach, meaning that the participants in the intervention group receives all daily food elements that they should consume

No Intervention: Control group

There is no intervention, patients are following their habitual diet

Outcome Measures

Primary Outcome Measures

Difference in change in 24-hour urine phosphorus excretion from baseline to week 26 between the two study groups [Baseline, day: 14, 30, 60, 90, 120, 150, 180 and three months after study completion]
24-hour urine sample

Secondary Outcome Measures

Difference in changes from baseline to week 26 between study groups in urinary excretion of calcium - creatinine, -urea and protein [Baseline, day: 14, 30, 60, 90, 120, 150, 180 and three months after study completion]
24-hour urine sample
Difference in changes from baseline to week 26 between study groups in blood lipids [Baseline, day: 14, 30, 60, 90, 120, 150, 180 and three months after study completion]
Blood samples
Difference in changes from baseline to week 26 between study groups in FGF23, Fractional excretion of phosphorus, P-phosphate, P-calcium, P-PTH, P-1,25OH2vitamin D3 and P-albumin [Baseline, day: 14, 30, 60, 90, 120, 150, 180 and three months after study completion]
Blood samples
Difference in changes from baseline to week 26 between study groups in glomerular filtration rate, as judged by P-creatinine [Baseline, day: 14, 30, 60, 90, 120, 150, 180 and three months after study completion]
Blood samples
Difference in changes from baseline to week 26 between study groups in weight [Baseline, day: 30, 60, 90, 120, 150, 180 and three months after study completion]
Weight changes in kilograms
Difference in changes from baseline to week 26 between study groups in hip- and waist circumferences [Baseline, day: 30, 60, 90, 120, 150, 180 and three months after study completion]
Hip/waist circumferences in centimeters
Difference in changes from baseline to week 26 between study groups in bone mineral density using DEXA scan (Dual-energy X-ray absorptiometry) [Baseline and study completion (day 180)]
Body composition, focusing on bone mineral density using DEXA scan (Dual-energy X-ray absorptiometry)
Difference in changes from baseline to week 26 between study groups in blood pressure, both systolic and diastolic blood pressure [Baseline, day: 30, 60, 90, 120, 150, 180 and three months after study completion]
Blood pressure mm Hg (systolic and diastolic)
Difference in changes from baseline to week 26 between study groups in quality of life [Baseline and study completion (day 180)]
Scale EQ-5D-5L questionnaire. Low/high scores varies in terms of reflecting better or worse outcomes
Dietary satisfaction in the intervention group [Day 30, 60, 90, 120, 150, 180]
5-likert scale questionnaire. Low/high scores varies in terms of reflecting better or worse outcomes
Difference in changes from baseline to week 26 between study groups in SuPAR and GDF15 [Baseline, day: 14, 30, 60, 90, 120, 150, 180 and three months after study completion]
Blood samples
Difference in change in metabolic acidosis from baseline to week 26 between the two study groups [Baseline, day: 14, 30, 60, 90, 120, 150, 180 and three months after study completion]
24-hour urine sample