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

January 24, 2020 updated by: Anna Solini, University of Pisa

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

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Pisa, Italy, 56125
        • University of Pisa

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dapaglifozin
People undergoing SGLT2i (Dapaglifozin) therapy
Drug: Dapagliflozin 10 MG
SGLT2-inhibitor: Diabetic oral drug with diuretic properties
Other Names:
  • DAPA
Experimental: Hydrochlorothiazide
People undergoing thiazide (Hydrochlorothiazide) therapy
Drug: Hydrochlorothiazide 12.5mg
Best known thiazide class diuretic.
Other Names:
  • HCT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Changes between baseline and 1 month
Urinary Phthalates concentration
Time Frame: Changes between baseline and 3 month
Exposure to phthalates assessed through urinary excretion spot and 24-hours
Changes between baseline and 3 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fasting glucose
Time Frame: 1 and 3 months
Fasting glucose measured in a fasting morning blood sample
1 and 3 months
Glycated Haemoglobin
Time Frame: 1 and 3 months
HbA1c in a fasting measured in a morning blood sample
1 and 3 months
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)
1 and 3 months
Macrovascular events
Time Frame: 1 and 3 months
Number of participants with MACE events (Stroke, Acute Myocardial Infarction, Unstable Angina, Revascularization)
1 and 3 months
Albumin excretion
Time Frame: 1 and 3 months
Measured by urinary albumin/creatinine ratio
1 and 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pisa

Investigators

  • Principal Investigator: Anna Solini, Prof, University of Pisa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 4, 2019

Primary Completion (Actual)

December 30, 2019

Study Completion (Anticipated)

April 1, 2020

Study Registration Dates

First Submitted

January 22, 2020

First Submitted That Met QC Criteria

January 24, 2020

First Posted (Actual)

January 27, 2020

Study Record Updates

Last Update Posted (Actual)

January 27, 2020

Last Update Submitted That Met QC Criteria

January 24, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PURITY - Protcol 5

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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