Phthalates Exposure in Type 2 Diabetic Patients and Diuretic Therapy

Phase 4

• Conditions: Renal Function Disorder; Glucose Metabolism Disorders
• Interventions: Drug: Dapagliflozin 10 MG; Drug: Hydrochlorothiazide 12.5mg

• Registration Number: NCT04242758
• Lead Sponsor: University of Pisa

Brief 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.

Study Timeline

• Study Start: 2019-06-04
• Primary Completion: 2019-12-30
• Status Verified: 2020-01
• Study First Submitted: 2020-01-22
• Study First Submitted QC: 2020-01-24
• Last Update Submitted: 2020-01-24
• Study First Posted: 2020-01-27
• Last Update Posted: 2020-01-27
• Study Completion: 2020-04-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Individuals of both sex;
• Age between 18 and 85 years;
• T2D
• T2D duration > 6 months
• BMI ≤ 40 Kg/m2,
• HbA1c > 48 mmol/mol
• Eligible for SGLT-2i therapy

Exclusion criteria

• age >85 years,
• eGFR <60 ml/min/1.73 m2,
• occurring acute complications

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dapaglifozin	Dapagliflozin 10 MG	People undergoing SGLT2i (Dapaglifozin) therapy
Hydrochlorothiazide	Hydrochlorothiazide 12.5mg	People undergoing thiazide (Hydrochlorothiazide) therapy

Primary Outcome Measures

Name	Time	Method
Urinary Phthalates concentration	Changes between baseline and 3 month	Exposure to phthalates assessed through urinary excretion spot and 24-hours

Secondary Outcome Measures

Name	Time	Method
Renal function	1 and 3 months	Using creatinine measured in a fasting morning blood sample and estimated by eGFR (calculated with the CDK-EPI formula)
Albumin excretion	1 and 3 months	Measured by urinary albumin/creatinine ratio
Macrovascular events	1 and 3 months	Number of participants with MACE events (Stroke, Acute Myocardial Infarction, Unstable Angina, Revascularization)
Fasting glucose	1 and 3 months	Fasting glucose measured in a fasting morning blood sample
Glycated Haemoglobin	1 and 3 months	HbA1c in a fasting measured in a morning blood sample

Trial Locations

Locations (1)

University of Pisa; 🇮🇹 Pisa, Italy