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

Type 2 Diabetes Clinical Trial

— UTI-flog  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04735042
• Other study ID #: AS0005
• Status: Recruiting
• Start date: October 7, 2020
• Est. completion date: April 7, 2022

Study information

• Verified date: January 2021
• Source: University of Pisa
• Contact: Anna Solini, MD, PhD
• Phone: 050993482
• Email: anna.solini[@]med.unipi.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: April 7, 2022
• Est. primary completion date: October 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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).

Related Conditions & MeSH terms

• Communicable Diseases
• Diabetes Mellitus, Type 2
• Infection
• Inflammation
• Type 2 Diabetes
• Urinary Tract Infections

Intervention

Drug:
• Empagliflozin / Linagliptin or Dapagliflozin/Saxagliptin Pill
association between SGLT2-inhibitor and DPP4-inhibitor
• Empagliflozin or Dapagliflozin Pill
SGLT2-inhibitor: diabetic oral drug with diuretic properties.

Locations

Country	Name	City	State
Italy	University of Pisa	Pisa

Sponsors (1)

Lead Sponsor	Collaborator
University of Pisa

Country where clinical trial is conducted

Italy, 

References & Publications (12)

Aswani SM, Chandrashekar U, Shivashankara K, Pruthvi B. Clinical profile of urinary tract infections in diabetics and non-diabetics. Australas Med J. 2014 Jan 31;7(1):29-34. doi: 10.4066/AMJ.2014.1906. eCollection 2014. — View Citation

Del Prato S, Rosenstock J, Garcia-Sanchez R, Iqbal N, Hansen L, Johnsson E, Chen H, Mathieu C. Safety and tolerability of dapagliflozin, saxagliptin and metformin in combination: Post-hoc analysis of concomitant add-on versus sequential add-on to metformin and of triple versus dual therapy with metformin. Diabetes Obes Metab. 2018 Jun;20(6):1542-1546. doi: 10.1111/dom.13258. Epub 2018 Mar 25. — View Citation

He K, Hu Y, Shi JC, Zhu YQ, Mao XM. Prevalence, risk factors and microorganisms of urinary tract infections in patients with type 2 diabetes mellitus: a retrospective study in China. Ther Clin Risk Manag. 2018 Feb 26;14:403-408. doi: 10.2147/TCRM.S147078. eCollection 2018. — View Citation

Kim NH, Yu T, Lee DH. The nonglycemic actions of dipeptidyl peptidase-4 inhibitors. Biomed Res Int. 2014;2014:368703. doi: 10.1155/2014/368703. Epub 2014 Jul 21. Review. — View Citation

Lewis DA, Brown R, Williams J, White P, Jacobson SK, Marchesi JR, Drake MJ. The human urinary microbiome; bacterial DNA in voided urine of asymptomatic adults. Front Cell Infect Microbiol. 2013 Aug 15;3:41. doi: 10.3389/fcimb.2013.00041. eCollection 2013. — View Citation

Li D, Wang T, Shen S, Fang Z, Dong Y, Tang H. Urinary tract and genital infections in patients with type 2 diabetes treated with sodium-glucose co-transporter 2 inhibitors: A meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2017 Mar;19(3):348-355. doi: 10.1111/dom.12825. Epub 2016 Dec 19. — View Citation

Liu J, Li L, Li S, Jia P, Deng K, Chen W, Sun X. Effects of SGLT2 inhibitors on UTIs and genital infections in type 2 diabetes mellitus: a systematic review and meta-analysis. Sci Rep. 2017 Jun 6;7(1):2824. doi: 10.1038/s41598-017-02733-w. Review. — View Citation

Masajtis-Zagajewska A, Nowicki M. New markers of urinary tract infection. Clin Chim Acta. 2017 Aug;471:286-291. doi: 10.1016/j.cca.2017.06.003. Epub 2017 Jun 13. Review. — View Citation

Nitzan O, Elias M, Chazan B, Saliba W. Urinary tract infections in patients with type 2 diabetes mellitus: review of prevalence, diagnosis, and management. Diabetes Metab Syndr Obes. 2015 Feb 26;8:129-36. doi: 10.2147/DMSO.S51792. eCollection 2015. Review. — View Citation

Renko M, Tapanainen P, Tossavainen P, Pokka T, Uhari M. Meta-analysis of the significance of asymptomatic bacteriuria in diabetes. Diabetes Care. 2011 Jan;34(1):230-5. doi: 10.2337/dc10-0421. Epub 2010 Oct 11. Review. — View Citation

Schmiemann G, Kniehl E, Gebhardt K, Matejczyk MM, Hummers-Pradier E. The diagnosis of urinary tract infection: a systematic review. Dtsch Arztebl Int. 2010 May;107(21):361-7. doi: 10.3238/arztebl.2010.0361. Epub 2010 May 28. Review. — View Citation

Yu H, Woo VC. Emerging use of combination therapies for the management of type 2 diabetes - focus on saxagliptin and dapagliflozin. Diabetes Metab Syndr Obes. 2017 Jul 21;10:317-332. doi: 10.2147/DMSO.S117982. eCollection 2017. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in metagenomic analysis based on rRNA 16S gene	Metagenomic analysis based on rRNA 16S gene will be performed by Novogene on Illumina platform (Hong Kong, China)	Each patients will be analyzed at baseline and after 12 weeks
Primary	Change from Baseline of total bacterial load	Absolute quantification of total bacterial load in the original sample using real-Time quantitative PCR	Each patients will be analyzed at baseline and after 12 weeks
Secondary	Fasting glucose	Fasting glucose measured in a fasting morning blood sample	baseline and 12 week
Secondary	Glycated Haemoglobin	HbA1c in a fasting measured in a morning blood sample	baseline and 12 week
Secondary	Renal function	Using creatinine measured in a fasting morning blood sample and estimated by eGFR (calculated with the CDK-EPI formula)	baseline and 12 week
Secondary	Albumin excretion	Measured by urinary albumin/creatinine ratio	baseline and 12 week
Secondary	Total cholesterol	Total cholesterol measured in a fasting morning blood sample	baseline and 12 week
Secondary	HDL cholesterol	HDL cholesterol measured in a fasting morning blood sample	baseline and 12 week
Secondary	Triglycerides	Triglycerides measured in a fasting morning blood sample	baseline and 12 week