Dietary Intervention Trial Targeting Metabolic Syndrome After Kidney Transplantation (DIETTX)

Dietary Intervention Trial Targeting Metabolic Syndrome After Renal Transplantation

Kidney transplant recipients (KTR) have a considerably lower life expectancy as compared with the general population, primarily due to a high prevalence of cardiovascular diseases. KTR often develop an unfavourable cardio-metabolic risk profile characterized by weight gain, metabolic syndrome and post-transplantation diabetes mellitus (PTDM). In general, nutrition plays a key role in both the prevention and treatment of these cardio-metabolic derangements.

However, in KTR most RCT's with a dietary intervention, failed to show significant improvement in cardio-metabolic health. This at least questions the efficacy of the diets of these intervention, which relied on general or diabetes guidelines, after kidney transplantation. KTR not only face a high cardio-metabolic risk, but also have a high risk for malnutrition and muscle mass depletion. More knowledge is required to determine the optimal diet and macronutrient composition for improvement of the cardio-metabolic risk factors in the context of the high malnutrition risk. In this regard, observational studies point towards the needs for a higher protein intake for better patient outcomes. Therefore, in this study, the investigators will examine if a high-protein, carbohydrate-reduced diet is more effective than a diet in line with the Dutch Dietary Guidelines for improvement of cardio-metabolic risk factors and for improvement of the body composition in KTR.

Study Overview

• Status: Not yet recruiting
• Conditions: Kidney Transplant; Complications
• Intervention / Treatment: Other: high-protein, carbohydrate-reduced diet; Other: Dutch Nutritional Guidelines

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years or older.
• Given informed consent.
• At least 6 months after kidney transplantation.
• Stable renal function with an estimated glomerular filtration rate (eGFR) > 30 mL/min.
• Raised systolic blood pressure (≥130 mmHg) and at least two more features of metabolic syndrome: central obesity (waist circumference ≥102 for men and ≥88cm for women), elevated triglycerides (≥ 1.7 mmol/L), reduced HDL-C (< 1.0 mmol/L for men and < 1.3 mmol/L for women) or on drug treatment for reduced HDL, elevated plasma glucose (≥ 5.6 mmol/L) or on drug treatment for elevated glucose9.
• Approval by nephrologist for participation in the study.

Exclusion Criteria:

• Active medical illness, including rejection of the graft.
• Psychopathology or serious cognitive impairment.
• Necessity to follow specific dietary measures for health purposes that conflict with the study diets.
• Use of insulin or sulfonylurea (SU)-derivates.
• Language barrier.
• Pregnancy or lactating.
• Serum potassium > 5.0 mmol/L that requires dietary measures.
• Moderate or severe malnutrition (Patient-Generated Subjective Global Assessment (PG-SGA) stage B or C). In this case, patient will be referred to a renal dietician.
• Participation in other intervention trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: high-protein, carbohydrate-reduced diet	Other: high-protein, carbohydrate-reduced diet; the high-protein, carbohydrate-reduced diet will consist of 1.2-1.4 g/kg/d protein, 26-20en% carbohydrates and +/- 50en% fatty acids, with mainly unsaturated fatty acids. This diet consist of mainly unprocessed, fresh nutrient-dense food-products. Ultra-processed foods and alcoholic beverages will be totally avoided. Salt consumption will not exceed 5-6 g/d. The diet is ad libitum and caloric restriction will not be applied. The diet will be followed for 6 weeks.
Active Comparator: Dutch Nutritional Guidelines	Other: Dutch Nutritional Guidelines; the diet according to the Dutch Nutritional Guidelines will consist of a protein intake of 0.8-1.0 g/kg/d and 50-60en% carbohydrates, and +/-30en% fatty acids, with restriction of saturated fatty acids <10en%. This diet consist of mainly unprocessed, fresh nutrient-dense food-products. Ultra-processed foods and alcoholic beverages will be totally avoided. Salt consumption will not exceed 5-6 g/d. The diet is ad libitum and caloric restriction will not be applied. The diet will be followed for 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic blood pressure	Change in systolic blood pressure (in mmHg)	before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardio-metabolic risk factors (lipids)	change in circulating triglyceride concentrations, low-density lipoprotein cholesterol (LDL-C) and HDL-C (in fasting serum levels) in mmol/L.	before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks)
Cardio-metabolic risk factors (diastolic blood pressure)	Change in diastolic blood pressure (in mmHg)	before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks)
Cardio-metabolic risk factors (waist circumference)	change in waist circumference (WC) in cm	before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks)
Cardio-metabolic risk factors (insulin resistance)	change in insulin resistance measuring by the homeostatic model assessment of insulin resistance (HOMA-IR index, fasting glucose, insulin)	before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks)
Body composition	change in fat and muscle mass measured by multi-frequency bio-electrical impedance analysis (BIA) BMI, weight	before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks)
Anthropometric measures	Change in weight in kilograms	before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks)
Anthropometric measures II	Change in Body Mass Index (BMI) in kilograms per square meter	before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks)
Body composition II	change in fat and muscle mass measured by multi-frequency bio-electrical impedance analysis (BIA)	before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks)
Quality of life (QoL)	change in QoL, 12-item short form health survey (SF-12)	before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks)
Fatigue	change in fatigue (measured by Dutch Checklist Individual Strength (CIS-20) questionnaire)	before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks)
Physical functioning	change in Hand Grip Strength (HSG)	before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks)
Physical functioning II	change in the five time sit to stand (FTSTS) test	before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks)
Nutritional intake	change in nutritional intake measured by a 3-day food diary	before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks)
Nutritional intake II	change in nutritional intake measured by nutritional intake biomarkers from 24-hour urine measurements (sodium, potassium, and urea excretion for calculating the protein intake by use of the Maroni equation)	before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks)

Collaborators and Investigators

• Sponsor: University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2021
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: December 23, 2020
• First Submitted That Met QC Criteria: January 5, 2021
• First Posted (Actual): January 6, 2021

Study Record Updates

• Last Update Posted (Actual): January 6, 2021
• Last Update Submitted That Met QC Criteria: January 5, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: kidney transplantation; metabolic syndrome; dietary intervention; high-protein diet
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Metabolic Syndrome
• Other Study ID Numbers: METc2020/050

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No