UTI-flog: SGLT-2 and DPP-4 Inhibition, Subclinical Inflammation of the Genito-urinary Tract and Risk of Infections.

Sponsor

University of Pisa (Other)

Overall Status

Recruiting

CT.gov ID

NCT04735042

Collaborator

(none)

Enrollment

Location

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In this observational study, 60 subjects with type 2 diabetes (T2D) and eligible, as per good clinical practice, for therapy with SGLT-2 inhibitor, will be randomized to receive a SGLT-2 inhibitor or a fixed dose combination of SGLT-2 inhibitor with a DPP4-inihibitor for 12 weeks. Measures will be performed at baseline and after 12 weeks of treatment, as per good clinical practice.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Urinary Tract Infections	Drug: Empagliflozin / Linagliptin or Dapagliflozin/Saxagliptin Pill Drug: Empagliflozin or Dapagliflozin Pill

Detailed Description

The day of the study patients undergo a routine clinical evaluation. Whole blood samples will be collected from an antecubital vein to assess serum/plasma aliquots of 200 μl each (frozen at -80°C until required for quantitation) for evaluation of biochemical parameters (fasting glucose, HbA1c, lipid profile, serum creatinine, uric acid, electrolytes, liver function enzymes, albumin).

A mid-stream first urine in the morning sample will be collected into a sterile container. 50 ml of urine will be immediately transferred into a sterile falcon and centrifugated at 4500 rpm for 10 min. After removal of the supernatant and addition of 10 ml of PBS or sterile physiological solution, the sample will be further centrifugated at 4500 rpm for 10 min. The supernatant will be removed and the pellet stored in a falcon at -80°C.

Genomic DNA will be extracted throw Qiamp DNA mini kit (QIAGEN) and quantified using spectrophotometric assay.

Study Design

Study Type:

Observational

Anticipated Enrollment :

60 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Use of Combination Empagliflozin/Linagliptin or Dapagliflozin/Saxagliptin vs Empagliflozin or Dapagliflozin Alone, Subclinical Inflammation of the Genito-urinary Tract and Risk of Infections.

Actual Study Start Date :

Oct 7, 2020

Anticipated Primary Completion Date :

Oct 7, 2021

Anticipated Study Completion Date :

Apr 7, 2022

Arms and Interventions

Arm	Intervention/Treatment
SGLT2 and DPP-4 inhibitors Patients undergoing SGLT2i and DPP4i.	Drug: Empagliflozin / Linagliptin or Dapagliflozin/Saxagliptin Pill association between SGLT2-inhibitor and DPP4-inhibitor Other Names: Glyxambi or Qtern
SGLT2 inhibitors only Patients undergoing SGLT2i alone.	Drug: Empagliflozin or Dapagliflozin Pill SGLT2-inhibitor: diabetic oral drug with diuretic properties. Other Names: Jardiance or Forxiga

Arm

Intervention/Treatment

SGLT2 and DPP-4 inhibitors

Patients undergoing SGLT2i and DPP4i.

Drug: Empagliflozin / Linagliptin or Dapagliflozin/Saxagliptin Pill

association between SGLT2-inhibitor and DPP4-inhibitor

Other Names:

Glyxambi or Qtern

SGLT2 inhibitors only

Patients undergoing SGLT2i alone.

Drug: Empagliflozin or Dapagliflozin Pill

SGLT2-inhibitor: diabetic oral drug with diuretic properties.

Other Names:

Jardiance or Forxiga

Outcome Measures

Primary Outcome Measures

Change from Baseline in metagenomic analysis based on rRNA 16S gene [Each patients will be analyzed at baseline and after 12 weeks]
Metagenomic analysis based on rRNA 16S gene will be performed by Novogene on Illumina platform (Hong Kong, China)
Change from Baseline of total bacterial load [Each patients will be analyzed at baseline and after 12 weeks]
Absolute quantification of total bacterial load in the original sample using real-Time quantitative PCR

Secondary Outcome Measures

Fasting glucose [baseline and 12 week]
Fasting glucose measured in a fasting morning blood sample
Glycated Haemoglobin [baseline and 12 week]
HbA1c in a fasting measured in a morning blood sample
Renal function [baseline and 12 week]
Using creatinine measured in a fasting morning blood sample and estimated by eGFR (calculated with the CDK-EPI formula)
Albumin excretion [baseline and 12 week]
Measured by urinary albumin/creatinine ratio
Total cholesterol [baseline and 12 week]
Total cholesterol measured in a fasting morning blood sample
HDL cholesterol [baseline and 12 week]
HDL cholesterol measured in a fasting morning blood sample
Triglycerides [baseline and 12 week]
Triglycerides measured in a fasting morning blood sample

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Type 2 diabetes diagnosis
Hb1Ac ≥ 7% and ≤ 9%

Exclusion Criteria:

Hb1Ac > 9%
current treatment with an SGLT2i or a DPP4i drugs, or in the prior 4 week
irritating and/or obstructive urinary or genital symptoms
menstrual cycle for women
current antibiotic treatment or in the prior 4 weeks
anatomical or functional abnormalities of the urinary tract (e.g. incontinence, neurological bladder, bladder prolapse).