Effect of Low Protein Diet on Top of Dapagliflozin on Chronic Kidney Disease in Patients With Type 2 Diabetes Mellitus (PRODAPA-CKD)

Effect of the Low PROtein Diet on Top of DAPAgliflozin and RAASi on the Progression of Chronic Kidney Disease in Patients With Type 2 Diabetes Mellitus

This is a prospective multicenter randomized controlled trial with a total duration of 36 months aiming to evaluate the effectiveness and the safety of low protein diet on top of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and renin-angiotensin-aldosterone inhibitors (RAASi) in reducing the progression of chronic kidney disease in patients with type 2 Diabetes Mellitus

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Diseases; Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Dapagliflozin 10 mg Tab; Behavioral: Low protein diet

Detailed Description

The KDIGO Diabetes in CKD Guideline (2020) recommends the use of SGLT2i (level 1A) and suggests (level 2C) the prescription of plant protein-based low-protein diet in patients with chronic kidney disease (CKD) and diabetes mellitus (DM). Both interventions have shown synergistic nephroprotective effects, slowing the progression of chronic kidney disease by reducing glomerular hyperfiltration and proteinuria, thus resulting the hypothesis that by combining these two interventions it could be possible to achieve a superior control over the progression of diabetic kidney disease.

The nutritional intervention will consist in a mild protein restriction (0.6 g/kg dry ideal body weight) and a total recommended energy intake of 30-35 kcal/kg of ideal dry body weight per day in all patients. The protein intake will be checked through the food diary and calculated based on urea from 24 hours urine collection.

The efficacy and safety parameters will be evaluated during follow-up visits at month 1,2,3,6,12 and 18.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Liliana Garneata, Professor; Phone Number: +40722619358; Email: lilianagarna@yahoo.com
• Study Contact Backup: Name: Elena Cuiban, PhD student; Phone Number: +40748975315; Email: elena.cuiban@drd.umfcd.ro

Study Locations

• Romania
  • Bucharest, Romania
    • Recruiting
    • Carol Davila University of Medicine and Pharmacy Bucharest
    • Contact: Liliana Garneata, Assoc Prof; Phone Number: +40722619358; Email: lilianagarna@yahoo.com
    • Contact: Elena Cuiban, MD; Phone Number: +40748975315; Email: elenacuiban@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age>18 years old
• confirmed chronic kidney disease (with eGFR between 60 and 20 ml/min/1.73 m2 and/or proteinuria >500 mg/g urinary creatinine) and confirmed type 2 Diabetes Mellitus
• stable kidney function for at least 12 weeks before enrollment (defined as decrease in eGFR < 5 ml/min/1.73 m2/year according to KDIGO 2012 guideline)
• treatment with ACE/ARBs and/or MRAs for at least 3 months
• no previous treatment with SGLT2i
• good nutritional status
• declared and anticipated good compliance with the prescribed diet
• signed informed consent

Exclusion Criteria:

• eGFR < 25 ml/min/1.73 m2
• poorly controlled arterial blood pressure (mean BP≥145/85 mm Hg)
• class IV NYHA heart failure, recent MACE (less than 6 months)
• relevant comorbid conditions (active infections (HBV, HCV, HIV), active neoplasia, digestive diseases with malabsorption, active autoimmune diseases/ immunosuppressive therapy)
• ADPKD
• kidney transplantation with functional graft
• malnutrition: BMI<18 kg/me, eight loss >10% during the last 6 months, serum albumin <3 g/dL
• feeding inability (anorexia, nausea)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Patients will receive a plant-based low protein diet (0.6 g proteins/kg ideal body weight per day) associated with Dapagliflozin 10 mg per day	Drug: Dapagliflozin 10 mg Tab; Dapagliflozin 10 mg once daily; Behavioral: Low protein diet; Plant based low protein diet (0.6 g/kg IBW)
Active Comparator: Control; Patients will receive Dapagliflozin 10 mg per day	Drug: Dapagliflozin 10 mg Tab; Dapagliflozin 10 mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the First Occurrence of Any of the Components of the Composite: ≥30% Sustained Decline in eGFR or Reaching ESRD or CV Death or Renal Death	End Stage Renal Disease (ESRD) is defined as: Sustained eGFR <15 mL/min/1.73m2 or,; Chronic dialysis treatment or,; Receiving a kidney transplant	12 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of decline in the estimated Glomerular Filtration Rate	Difference between eGFR at any timepoint and the initial eGFR	month 3, 9 and12 after randomization
Variation of albuminuria	Difference between albuminuria at at any timepoint and the initial albuminuria (expressed as albumin to creatinine ratio)	month 3, 9 and12 after randomization
Variation of HbA1C	Difference between HbA1C at at any timepoint and the initial HbA1C	month 3, 9 and12 after randomization
Variation of serum cholesterol levels	Difference between serum cholesterol at at any timepoint and the initial serum cholesterol	month 3, 9 and12 after randomization
Variation of serum bicarbonate levels	Difference between serum bicarbonate at at any timepoint and the initial serum bicarbonate	month 3, 9 and12 after randomization
Variation of serum potassium levels	Difference between serum potassium at at any timepoint and the initial serum potassium	month 3, 9 and12 after randomization
Variation of serum sodium levels	Difference between serum sodium at at any timepoint and the initial serum sodium	month 3, 9 and12 after randomization
Variation of hemoglobin levels	Difference between hemoglobin at at any timepoint and the initial serum hemoglobin	month 3, 9 and12 after randomization
Variation of hematocrit levels	Difference between hematocrit at at any timepoint and the initial hematocrit	month 3, 9 and12 after randomization
All cause hospitalizations	Percentage of patients who experienced hospitalizations of all cause	12 months after randomization
Variation in body weight	Difference between body weight at at any timepoint and the body weight	month 3, 9 and12 after randomization
Variation in BMI	Difference between BMI at at any timepoint and the initial BMI	month 3, 9 and12 after randomization
Variation in handgrip strength	Difference between handgrip strength at at any timepoint and the initial handgrip strength	month 3, 9 and12 after randomization
Variation in serum albumin levels	Difference between serum albumin at at any timepoint and the initial serum albumin	month 3, 9 and12 after randomization
Variation in CRP levels	Difference between CRP at at any timepoint and the initial CRP	month 3, 9 and12 after randomization
Changes in the quality of life	Evaluated by SF-36 questionaire	month 3, 9 and12 after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compliance to the protein intake	Achieved protein intake will be estimated based on urinary urea excretion, using Mitch-Maroni's formula	month 1, 3, 9 and12 after randomization
Compliance to the energy intake	Achieved energy intake will be estimated using the 3-day food diary to calculate the daily energy intake	month 1, 3, 9 and12 after randomization
Compliance to carbohydrate intake	Achieved energy intake will be estimated by the 3-day food diary to calculate thecarbohydrates intake	month 1, 3, 9 and12 after randomization

Collaborators and Investigators

• Sponsor: Anemia Working Group Romania
• Collaborators: Carol Davila University of Medicine and Pharmacy; Sf Ioan Emergency Clinical Hospital, Nephrology and Dialysis Department, Bucharest, Romania; Dr Carol Davila Teaching Hospital of Nephrology, Nephrology Department, Bucharest, Romania
• Investigators: Principal Investigator: Liliana Garneata, Professor, Carol Davila University of Medicine and Pharmacy Bucharest, Romania

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: February 11, 2024
• First Submitted That Met QC Criteria: February 20, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: chronic kidney disease; nutrition therapy; low protein diet
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Renal Insufficiency, Chronic; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: 01/2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No