NCT04242758

Phthalates Exposure in Type 2 Diabetic Patients and Diuretic Therapy

Exploring the Association Between Phthalates Exposure, Measured Through Their Urinary Metabolites, and Renal Function Impairment in Individuals With TYpe 2 Diabetes - SGLT2 Subprotocol

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: University of Pisa · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

In this open clinical trial, 30 subjects with inadequately controlled T2D and eligible, as per good clinical practice, for therapy with SGLT-2 inhibitor, will be randomized to receive a SGLT-2 inhibitor vs other oral-antidiabetic drugs (OADs) therapy for 3 months. Measures will be performed at baseline, after 2 days, after one month and at the end of the study protocol, as per good clinical practice

Detailed description

* Total concentrations of MEHP, MEOHP and MEHHP will be quantified, in the laboratories of the Institute of Clinical Physiology, National Research Council, Pisa, in a spot morning urine sample by ultra-HPLC coupled with electrospray ionization/quadrupole time-of-flight mass spectrometry (Agilent UHPLC 1290 infinity coupled to an Agilent 6540 MS-QTOF, Santa Clara, CA) using stable isotope labeled substrates, i.e. MEHP (ring-1,2-13C2, dicarboxyl-13C2), MEHHP, MEHHP 13C4, MEOHP and MEOHP 13C4 that will be purchased from Cambridge Isotope Laboratories (Tewksbury, MA). * Urinary creatinine concentrations will be measured to adjust urinary concentrations of DEHP metabolite (Beckman Coulter AU400, Brea, CA), thus minimizing the influence of urine volume. * Serum and urinary inflammatory markers and adipocytokines will be quantitatively determined using sandwich enzyme-linked immunosorbent assays kits according to the manufacturer's instructions. Optical density will be measured using a microplate reader. * Serum and urinary markers of oxidative stress will be measured by gold standard techniques. In detail, MDA will be quantified by TBARS reactive substances measured by optical density; GSH-Px by a specific assay kit according to the manufacturer's instruction; SOD activity will be determined using a specific SOD kit; urinary 8-isoprostane concentration will be measured by a specific affinity sorbent. (Cayman Chemical, Ann Harbor, MI, USA) according to the manufacturer's instructions. * To analyze mitochondrial DNA we will apply a triplex design previously reported to amplify mitochondria loci located within the MinorArc and MajorArc, respectively. To assess nuclear DNA, we will use RNase P Copy Number Reference. * The phthalates-free diet will be self-administered by the individuals under intervention, following a set of instruction and rules provided by the physicians based on the current literature data.

Conditions

• Renal Function Disorder
• Glucose Metabolism Disorders

Interventions

Type	Name	Description
DRUG	Dapagliflozin 10 MG	SGLT2-inhibitor: Diabetic oral drug with diuretic properties
DRUG	Hydrochlorothiazide 12.5mg	Best known thiazide class diuretic.

Timeline

• Start date: 2019-06-04
• Primary completion: 2019-12-30
• Completion: 2020-04-01
• First posted: 2020-01-27
• Last updated: 2020-01-27

Locations

1 site across 1 country: Italy