Association Between Phthalates Exposure and Renal Function Impairment in TYpe 2 Diabetes (PURITY-2)

August 8, 2018 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 - Protocol 2

The global incidence of diabetic nephropathy (DN) is increasing, with no appreciable reduction in the percent of patients progressing toward end stage renal disease (ESRD) and dialysis (Tuttle et al, 2014, Winocour et al, 2018). Therefore, identification of modifiable risk factors and early biomarkers of progressive decline in kidney function is an urgent clinical need. Phthalates are environmental and dietary contaminants with a various array of use that are identified in many consumer and industrial products; among them, di-(2-ethylhexyl) phthalate (DEHP) and its metabolites (mono 2-ethylhexyl phthalate (MEHP), 5OH-MEHP (MEHHP) and 5oxo-MEHP (MEOHP)) are widely used (Kato et al 2004, Braun et al, 2013). They partially distribute to the human tissues and their urinary and serum levels are directly related; therefore, urinary concentration of phthalates is commonly used as proxy of their exposure in humans (Kato et al 2004).

While the association between phthalates exposure and development of T2D is currently being explored (Dong et al 2017, Dales et al, 2018), little is known about their role in DN. Recent observations show that DEHP and its metabolites are associated with a higher prevalence of low-grade albuminuria and in children exposed to higher phthalates concentrations (Trasande et al, 2014, Wu et al, 2018), however such association has yet to be verified in adults. The environmental ubiquity of the phthalates enhances the importance of investigating the potential relation between their exposure and different degrees of renal function. (Kato et al 2004, Kataria et al, 2015).

Given this premise, the investigators will explore this potential association in a population of subjects with T2D consecutively referring to the outpatient diabetes clinic in Santa Chiara Hospital, Pisa, enrolled on a volunteer basis. During their routine visit at Santa Chiara Hospital outpatient diabetes clinic participants will provide the results of blood tests prescribed as per standard clinical practice along with a first morning, overnight fasting, urine sample collected in a phthalates-free container.

The investigators will record the participants' clinical history, physical examination and anthropometric measurements, will measure their renal function, evaluated by eGFR (calculated with the CDK-EPI formula), albumin excretion, fasting glucose, HbA1c%, and the exposure to phthalates, assessed by total concentrations of MEHP, MEOHP, MEHHP and adjusted for urinary creatinine. In this way, the investigators aim to point out the relationship of urinary phthalates with higher degrees of albuminuria and/or lower eGFR after adjustment for all potential confounders, including therapies.

Study Overview

Status

Unknown

Conditions

Study Type

Observational

Enrollment (Anticipated)

200

Contacts and Locations

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

Study Contact

  • Name: Anna Solini, Associate Professor, MD, PhD
  • Phone Number: +39 050993482
  • Email: anna.solini@med.unipi

Study Contact Backup

Study Locations

  • Italy
      • Pisa, Italy, 56125
        • University of Pisa
        • Contact:
        • Contact:
        • Principal Investigator:
          • Anna Solini, Associate Professor, MD, PhD
        • Sub-Investigator:
          • Amalia Gastaldelli, Associate Professor, PhD
        • Sub-Investigator:
          • Alessandro Mengozzi, MD

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

Sampling Method

Probability Sample

Study Population

Type 2 diabetes individuals referring to our outpatient clinics

Description

Inclusion Criteria:

Age 18-85 years, T2D diagnosis, T2D duration >6 months,

Exclusion Criteria:

occurring acute clinical conditions, eGFR <15 ml/min/1.73m2, BMI > 40 Kg/m2.

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

Cohorts and Interventions

Group / Cohort
Type 2 diabetes subjects
Type 2 diabetes subjects consecutively referring to Santa Chiara, Pisa diabetes outpatients clinic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phthalates exposure [ug/g]
Time Frame: Single routine clinical visit
Concentrations of metabolites of DEHP [ug/ml] in a first morning spot urine sample (obtained during clinical visit) measured by ultra-HPLC coupled with electrospray ionization/quadrupole time-of-flight MS and then normalized for urinary creatinine [g/ml].
Single routine clinical visit
Albuminuria [mg/g]
Time Frame: Single routine clinical visit
Grade of albuminuria measured by albuminuria/creatininuria ratio [mg/g] in a first morning spot urine sample (obtained during clinical visit).
Single routine clinical visit
Glomerular Filtration Rate [ml/min/1.73m2]
Time Frame: Single routine clinical visit
GFR measured by eGFR (calculated with CDK-EPI formula). Creatinine [mg/dL] is measured in a serum sample (obtained during clinical visit). Physiological parameters (age, sex, race) are obtained during clinical visit.
Single routine clinical visit

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CV Events (Yes/No)
Time Frame: Single routine clinical visit
History of cardiovascular events (Non fatal: Acute Myocardial infarction, Unstable Angina, Stroke), evaluated by clinical interview during routine clinical visit.
Single routine clinical visit

Collaborators and Investigators

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

Sponsor

University of Pisa

Collaborators

Istituto di Fisiologia Clinica CNR

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 (Anticipated)

August 10, 2018

Primary Completion (Anticipated)

September 3, 2018

Study Completion (Anticipated)

September 3, 2018

Study Registration Dates

First Submitted

August 6, 2018

First Submitted That Met QC Criteria

August 8, 2018

First Posted (Actual)

August 9, 2018

Study Record Updates

Last Update Posted (Actual)

August 10, 2018

Last Update Submitted That Met QC Criteria

August 8, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PURITY - Protocol 2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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.

Clinical Trials on Diabetes Mellitus, Type 2

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Congo

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe