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Phthalates Exposure in Type 2 Diabetic Patients and Diuretic Therapy (PURITY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04242758
Recruitment Status : Active, not recruiting
First Posted : January 27, 2020
Last Update Posted : January 27, 2020
Information provided by (Responsible Party):
Anna Solini, 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

Condition or disease Intervention/treatment Phase
Renal Function Disorder Glucose Metabolism Disorders Drug: Dapagliflozin 10 MG Drug: Hydrochlorothiazide 12.5mg Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Exploring the Association Between Phthalates Exposure, Measured Through Their Urinary Metabolites, and Renal Function Impairment in Individuals With TYpe 2 Diabetes - SGLT2 Subprotocol
Actual Study Start Date : June 4, 2019
Actual Primary Completion Date : December 30, 2019
Estimated Study Completion Date : April 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Tests

Arm Intervention/treatment
Experimental: Dapaglifozin
People undergoing SGLT2i (Dapaglifozin) therapy
Drug: Dapagliflozin 10 MG
SGLT2-inhibitor: Diabetic oral drug with diuretic properties
Other Name: DAPA

Experimental: Hydrochlorothiazide
People undergoing thiazide (Hydrochlorothiazide) therapy
Drug: Hydrochlorothiazide 12.5mg
Best known thiazide class diuretic.
Other Name: HCT

Primary Outcome Measures :
  1. Urinary Phthalates concentration [ Time Frame: Changes between baseline and 1 month ]
    Exposure to phthalates assessed through urinary concentration of phthalates metabolites spot and 24-hours

  2. Urinary Phthalates concentration [ Time Frame: Changes between baseline and 3 month ]
    Exposure to phthalates assessed through urinary excretion spot and 24-hours

Secondary Outcome Measures :
  1. Fasting glucose [ Time Frame: 1 and 3 months ]
    Fasting glucose measured in a fasting morning blood sample

  2. Glycated Haemoglobin [ Time Frame: 1 and 3 months ]
    HbA1c in a fasting measured in a morning blood sample

  3. Renal function [ Time Frame: 1 and 3 months ]
    Using creatinine measured in a fasting morning blood sample and estimated by eGFR (calculated with the CDK-EPI formula)

  4. Macrovascular events [ Time Frame: 1 and 3 months ]
    Number of participants with MACE events (Stroke, Acute Myocardial Infarction, Unstable Angina, Revascularization)

  5. Albumin excretion [ Time Frame: 1 and 3 months ]
    Measured by urinary albumin/creatinine ratio

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04242758

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University of Pisa
Pisa, Italy, 56125
Sponsors and Collaborators
University of Pisa
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Principal Investigator: Anna Solini, Prof University of Pisa

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Responsible Party: Anna Solini, Associate Professor, University of Pisa Identifier: NCT04242758    
Other Study ID Numbers: PURITY - Protcol 5
First Posted: January 27, 2020    Key Record Dates
Last Update Posted: January 27, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Metabolic Diseases
Glucose Metabolism Disorders
Pathologic Processes
Antihypertensive Agents
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Sodium-Glucose Transporter 2 Inhibitors
Hypoglycemic Agents