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

Phase 4
Recruiting
Conditions
Chronic Kidney Diseases
Type 2 Diabetes Mellitus
Interventions
Behavioral: Low protein diet
Registration Number
NCT06281899
Lead Sponsor
Anemia Working Group Romania
Brief 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

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
200
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ControlDapagliflozin 10 mg TabPatients will receive Dapagliflozin 10 mg per day
InterventionLow protein dietPatients 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
InterventionDapagliflozin 10 mg TabPatients 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
Primary Outcome Measures
NameTimeMethod
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 Death12 months after randomization

End Stage Renal Disease (ESRD) is defined as:

* Sustained eGFR \<15 mL/min/1.73m2 or,

* Chronic dialysis treatment or,

* Receiving a kidney transplant

Secondary Outcome Measures
NameTimeMethod
Rate of decline in the estimated Glomerular Filtration Ratemonth 3, 9 and12 after randomization

Difference between eGFR at any timepoint and the initial eGFR

Variation of albuminuriamonth 3, 9 and12 after randomization

Difference between albuminuria at at any timepoint and the initial albuminuria (expressed as albumin to creatinine ratio)

Variation of HbA1Cmonth 3, 9 and12 after randomization

Difference between HbA1C at at any timepoint and the initial HbA1C

Variation of serum bicarbonate levelsmonth 3, 9 and12 after randomization

Difference between serum bicarbonate at at any timepoint and the initial serum bicarbonate

Variation of serum sodium levelsmonth 3, 9 and12 after randomization

Difference between serum sodium at at any timepoint and the initial serum sodium

Variation of hematocrit levelsmonth 3, 9 and12 after randomization

Difference between hematocrit at at any timepoint and the initial hematocrit

All cause hospitalizations12 months after randomization

Percentage of patients who experienced hospitalizations of all cause

Variation of serum cholesterol levelsmonth 3, 9 and12 after randomization

Difference between serum cholesterol at at any timepoint and the initial serum cholesterol

Variation in body weightmonth 3, 9 and12 after randomization

Difference between body weight at at any timepoint and the body weight

Variation in BMImonth 3, 9 and12 after randomization

Difference between BMI at at any timepoint and the initial BMI

Variation in handgrip strengthmonth 3, 9 and12 after randomization

Difference between handgrip strength at at any timepoint and the initial handgrip strength

Variation in serum albumin levelsmonth 3, 9 and12 after randomization

Difference between serum albumin at at any timepoint and the initial serum albumin

Variation in CRP levelsmonth 3, 9 and12 after randomization

Difference between CRP at at any timepoint and the initial CRP

Changes in the quality of lifemonth 3, 9 and12 after randomization

Evaluated by SF-36 questionaire

Variation of serum potassium levelsmonth 3, 9 and12 after randomization

Difference between serum potassium at at any timepoint and the initial serum potassium

Variation of hemoglobin levelsmonth 3, 9 and12 after randomization

Difference between hemoglobin at at any timepoint and the initial serum hemoglobin

Trial Locations

Locations (1)

Carol Davila University of Medicine and Pharmacy Bucharest

🇷🇴

Bucharest, Romania

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