Single-center, randomized, controlled study to evaluate the effects of a six-month treatment with renal glucose transport inhibitor (SGLT2i) drugs on markers of senescence, inflammation and tubulointerstitial damage in the kidney of patients with chronic kidney disease with or without type 2 diabetes

Phase 1

• Conditions: Chronic Kidney Deseas; MedDRA version: 21.1Level: LLTClassification code 10050441Term: Chronic renal insufficiencySystem Organ Class: 100000004857; Therapeutic area: Body processes [G] - Reproductive physiologi cal processes [G08]

• Registration Number: EUCTR2020-004835-26-IT
• Lead Sponsor: IRCCS-A.O.U. SAN MARTINO-IST

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-02
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

- Adult (age 18-75 years)
- Albuminuria defined as urinary albumin ratio: creatinine = 25 mg / g (or protein ratio: creatinine = 30 mg / g) or albuminuria> 30 mg / 24h
- eGFR> 25 and <75 ml / minute 1.73 m2
- BMI between 19 kg / m2 and 30 kg / m2
- Treatment with an ACE inhibitor and / or ARB at the maximum tolerated dose (for the individual subject). The maximum tolerated dose for an individual subject may be less than the maximum labeled dose or may be zero if the medical reason is documented.
- Mean systolic and diastolic blood pressure (determined as the average of three repeated measurements) should be <180/90 mmHg
- Willingness to participate in the study (signing of informed consent)

Specific inclusion criteria

CKD AND T2DM
- Clinical diagnosis of T2DM for at least 1 year
- Value of hemoglobin A1c (HbA1c) <9.5%
-Patients treated only with metformin and/or repaglinide
- Diagnosis of diabetic nephropathy after renal biopsy made not more than 6 months before the screening visit (only for the subgroup of patients candidates for the second renal biopsy)
- Proteinuria> 1g / 24h (only for the subgroup of patients candidates for the second renal biopsy)
- Hemoglobin A1c (HbA1c) value> 6.5% (only for patients candidates for the second renal biopsy)

CKD WITHOUT T2DM
diagnosed with hypertension for at least 5 years
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 19
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 19

Exclusion Criteria

•Type 1 Diabetes
•Hemoglobin A1c (HbA1c) value of > 9.5% during the Screening period (based on central laboratory measurement).
• need for an adjunctive drugs on top on metformin and repaglinide
•Hemoglobin A1c (HbA1c) value of < 6.5% only for patients candidated to the second kidney biopsy
•Estimated glomerular filtration rate < 25 or > 75 ml/min/1.73m2 (according to the CKD-EPI) at screening
•Untreated urinary or genital infection at screening and follow-up
•Clear signs of volume depletion
•Symptomatic hypotension, or systolic blood pressure < 90 or non-controlled hypertension
•History of alcohol or drug abuse, anuria, dialysis, or acute kidney injury/acute renal failure in the 3 months prior to Screening Period
•Heart, liver or kidney transplant
•Acute coronary syndrome, stroke, or transient ischemic attack within 3 months prior to informed consent
•Liver disease, defined by serum levels of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal (ULN) during screening
•Planned cardiac surgery or angioplasty within 3 months
•Cancer or medical history of cancer (except for basal cell carcinoma) within the last 5 years
•Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at time of screening leading to unstable body weight (e.g. surgery, aggressive diet regimen, etc.)
•SGLT2i treatment in the 10 weeks before the Screening Period
•Treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent
•Any uncontrolled endocrine disorder except T2DM
•Women who are pregnant or breastfeeding
•Pre-menopausal women of child bearing potential who are not willing to employ effective contraception according to 2007 CTFG Recommendations related to contraception and pregnancy testing in clinical trials from screening for all the duration of the study
•Patients with a known hypersensitivity to Dapagliflozin or other SGLT2- inhibitors, including hypersensitivity to excipients (e.g. lactose)
•History of pancreatitis, or pancreatic surgery, diabetic ketoacidosis
•Prior lower extremity amputation or current threat of amputation (eg, lower extremity ulcer and peripheral artery disease)
•History of severe hypoglycaemia and hypoglycaemia unawareness.
•Contraindication to MRI

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified