Clinical trial NCT06281899: Effect of Low Protein Diet on Top of Dapagliflozin on Chronic Kidney Disease in Patients With Type 2 Diabetes Mellitus
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Chronic Kidney Diseases
Type 2 Diabetes Mellitus
Keywords: chronic kidney disease
low protein diet
nutrition therapy
Lead sponsor: Anemia Working Group Romania
Sponsor class: OTHER
Collaborators: name: Sf Ioan Emergency Clinical Hospital, Nephrology and Dialysis Department, Bucharest, Romania
name: Dr Carol Davila Teaching Hospital of Nephrology, Nephrology Department, Bucharest, Romania
name: Carol Davila University of Medicine and Pharmacy
First posted: 2024-02-28
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: 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
timeFrame: 12 months after randomization
Secondary outcomes:
measure: Rate of decline in the estimated Glomerular Filtration Rate
timeFrame: month 3, 9 and12 after randomization
measure: Variation of albuminuria
timeFrame: month 3, 9 and12 after randomization
measure: Variation of HbA1C
timeFrame: month 3, 9 and12 after randomization
measure: Variation of serum cholesterol levels
timeFrame: month 3, 9 and12 after randomization
measure: Variation of serum bicarbonate levels
timeFrame: month 3, 9 and12 after randomization
measure: Variation of serum potassium levels
timeFrame: month 3, 9 and12 after randomization
measure: Variation of serum sodium levels
timeFrame: month 3, 9 and12 after randomization
measure: Variation of hemoglobin levels
timeFrame: month 3, 9 and12 after randomization
measure: Variation of hematocrit levels
timeFrame: month 3, 9 and12 after randomization
measure: All cause hospitalizations
timeFrame: 12 months after randomization
measure: Variation in body weight
timeFrame: month 3, 9 and12 after randomization
measure: Variation in BMI
timeFrame: month 3, 9 and12 after randomization
measure: Variation in handgrip strength
timeFrame: month 3, 9 and12 after randomization
measure: Variation in serum albumin levels
timeFrame: month 3, 9 and12 after randomization
measure: Variation in CRP levels
timeFrame: month 3, 9 and12 after randomization
measure: Changes in the quality of life
timeFrame: month 3, 9 and12 after randomization
Other outcomes:
measure: Compliance to the protein intake
timeFrame: month 1, 3, 9 and12 after randomization
measure: Compliance to the energy intake
timeFrame: month 1, 3, 9 and12 after randomization
measure: Compliance to carbohydrate intake
timeFrame: month 1, 3, 9 and12 after randomization
Locations:
city: Bucharest
country: Romania
facility: Carol Davila University of Medicine and Pharmacy Bucharest
Study officials:
affiliation: Carol Davila University of Medicine and Pharmacy Bucharest, Romania
name: Liliana Garneata, Professor
role: PRINCIPAL_INVESTIGATOR
References: