Effect of Low Protein Diet on Top of Dapagliflozin on Chronic Kidney Disease in Patients With Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus Clinical Trial

— PRODAPA-CKD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06281899
• Other study ID #: 01/2022
• Status: Recruiting
• Phase: Phase 4
• Start date: January 1, 2022
• Est. completion date: March 31, 2025

Study information

• Verified date: February 2024
• Source: Anemia Working Group Romania
• Contact: Liliana Garneata, Professor
• Phone: +40722619358
• Email: lilianagarna[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: March 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Kidney Diseases
• Renal Insufficiency, Chronic
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Dapagliflozin 10 mg Tab
Dapagliflozin 10 mg once daily

Behavioral:
• Low protein diet
Plant based low protein diet (0.6 g/kg IBW)

Locations

Country	Name	City	State
Romania	Carol Davila University of Medicine and Pharmacy Bucharest	Bucharest

Sponsors (4)

Lead Sponsor	Collaborator
Anemia Working Group Romania	Carol Davila University of Medicine and Pharmacy, Dr Carol Davila Teaching Hospital of Nephrology, Nephrology Department, Bucharest, Romania, Sf Ioan Emergency Clinical Hospital, Nephrology and Dialysis Department, Bucharest, Romania

Country where clinical trial is conducted

Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	Variation of HbA1C	Difference between HbA1C at at any timepoint and the initial HbA1C	month 3, 9 and12 after randomization
Secondary	Variation of serum cholesterol levels	Difference between serum cholesterol at at any timepoint and the initial serum cholesterol	month 3, 9 and12 after randomization
Secondary	Variation of serum bicarbonate levels	Difference between serum bicarbonate at at any timepoint and the initial serum bicarbonate	month 3, 9 and12 after randomization
Secondary	Variation of serum potassium levels	Difference between serum potassium at at any timepoint and the initial serum potassium	month 3, 9 and12 after randomization
Secondary	Variation of serum sodium levels	Difference between serum sodium at at any timepoint and the initial serum sodium	month 3, 9 and12 after randomization
Secondary	Variation of hemoglobin levels	Difference between hemoglobin at at any timepoint and the initial serum hemoglobin	month 3, 9 and12 after randomization
Secondary	Variation of hematocrit levels	Difference between hematocrit at at any timepoint and the initial hematocrit	month 3, 9 and12 after randomization
Secondary	All cause hospitalizations	Percentage of patients who experienced hospitalizations of all cause	12 months after randomization
Secondary	Variation in body weight	Difference between body weight at at any timepoint and the body weight	month 3, 9 and12 after randomization
Secondary	Variation in BMI	Difference between BMI at at any timepoint and the initial BMI	month 3, 9 and12 after randomization
Secondary	Variation in handgrip strength	Difference between handgrip strength at at any timepoint and the initial handgrip strength	month 3, 9 and12 after randomization
Secondary	Variation in serum albumin levels	Difference between serum albumin at at any timepoint and the initial serum albumin	month 3, 9 and12 after randomization
Secondary	Variation in CRP levels	Difference between CRP at at any timepoint and the initial CRP	month 3, 9 and12 after randomization
Secondary	Changes in the quality of life	Evaluated by SF-36 questionaire	month 3, 9 and12 after randomization