Diabetes Mellitus, Type 2PURITY-2NCT03622957
Association Between Phthalates Exposure and Renal Function Impairment in TYpe 2 Diabetes
An observational study of Diabetes Mellitus, Type 2 and Albuminuria, run by University of Pisa at 1 site in Italy.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Diabetes Mellitus, Type 2, Albuminuria, Cardiovascular Risk Factor
- How many people
- 200 participants
- Where
- 1 siteItaly
- Study dates
- 10 Aug 2018to 3 Sep 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Type 2 diabetes individuals referring to our outpatient clinics
Who may be able to join
- Age 18-85 years, T2D diagnosis, T2D duration >6 months,
Who cannot join
- occurring acute clinical conditions, eGFR <15 ml/min/1.73m2, BMI > 40 Kg/m2.
Trial locations and contacts
1 site in 1 country.
Italy1 site
University of Pisa
Pisa, 56125
Anna Solini, Associate Professor, MD, PhD, +39 050993482, anna.solini@med.unipi.it
Alessandro Mengozzi, MD, +39 050993640, alessandro.mengozzi@medmcs.unipi.it
About this study
Official title: 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).
Read more
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.
- Medical subject headings
- Diabetes Mellitus, Type 2, Albuminuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Type 2 diabetes subjects | Type 2 diabetes subjects consecutively referring to Santa Chiara, Pisa diabetes outpatients clinic |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phthalates exposure [ug/g]
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].
Measured: Single routine clinical visit
Albuminuria [mg/g]
Grade of albuminuria measured by albuminuria/creatininuria ratio [mg/g] in a first morning spot urine sample (obtained during clinical visit).
Measured: Single routine clinical visit
Glomerular Filtration Rate [ml/min/1.73m2]
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.
Measured: Single routine clinical visit
Secondary outcomes (1)
CV Events (Yes/No)
History of cardiovascular events (Non fatal: Acute Myocardial infarction, Unstable Angina, Stroke), evaluated by clinical interview during routine clinical visit.
Measured: Single routine clinical visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2018
- Study start10 Aug 2018 (estimated)
- Primary completion3 Sep 2018 (estimated)
- Study completion3 Sep 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pisa
- Sponsor type
- University, hospital or other
- Collaborators
- Istituto di Fisiologia Clinica CNR
- Responsible party
- Principal investigator, Anna Solini, University of Pisa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03622957
- Sponsor's protocol ID
- PURITY - Protocol 2
- Acronym
- PURITY-2
- Status last verified
- Aug 2018
- First submitted
- 6 Aug 2018
- Last updated
- 10 Aug 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Tuttle KR, Bakris GL, Bilous RW, Chiang JL, de Boer IH, Goldstein-Fuchs J, Hirsch IB, Kalantar-Zadeh K, Narva AS, Navaneethan SD, Neumiller JJ, Patel UD, Ratner RE, Whaley-Connell AT, Molitch ME. Diabetic kidney disease: a report from an ADA Consensus Conference. Diabetes Care. 2014 Oct;37(10):2864-83. doi: 10.2337/dc14-1296.
PubMed 25249672Winocour PH. Diabetes and chronic kidney disease: an increasingly common multi-morbid disease in need of a paradigm shift in care. Diabet Med. 2018 Mar;35(3):300-305. doi: 10.1111/dme.13564. Epub 2018 Jan 8.
PubMed 29247554Kato K, Silva MJ, Reidy JA, Hurtz D 3rd, Malek NA, Needham LL, Nakazawa H, Barr DB, Calafat AM. Mono(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-oxohexyl) phthalate as biomarkers for human exposure assessment to di-(2-ethylhexyl) phthalate. Environ Health Perspect. 2004 Mar;112(3):327-30. doi: 10.1289/ehp.6663.
PubMed 14998748Braun JM, Sathyanarayana S, Hauser R. Phthalate exposure and children's health. Curr Opin Pediatr. 2013 Apr;25(2):247-54. doi: 10.1097/MOP.0b013e32835e1eb6.
PubMed 23429708Dong R, Zhao S, Zhang H, Chen J, Zhang M, Wang M, Wu M, Li S, Chen B. Sex Differences in the Association of Urinary Concentrations of Phthalates Metabolites with Self-Reported Diabetes and Cardiovascular Diseases in Shanghai Adults. Int J Environ Res Public Health. 2017 Jun 5;14(6):598. doi: 10.3390/ijerph14060598.
PubMed 28587233Dales RE, Kauri LM, Cakmak S. The associations between phthalate exposure and insulin resistance, beta-cell function and blood glucose control in a population-based sample. Sci Total Environ. 2018 Jan 15;612:1287-1292. doi: 10.1016/j.scitotenv.2017.09.009. Epub 2017 Sep 8.
PubMed 28898934Trasande L, Sathyanarayana S, Trachtman H. Dietary phthalates and low-grade albuminuria in US children and adolescents. Clin J Am Soc Nephrol. 2014 Jan;9(1):100-9. doi: 10.2215/CJN.04570413. Epub 2013 Oct 31.
PubMed 24178978Wu CF, Hsiung CA, Tsai HJ, Tsai YC, Hsieh HM, Chen BH, Wu MT. Interaction of melamine and di-(2-ethylhexyl) phthalate exposure on markers of early renal damage in children: The 2011 Taiwan food scandal. Environ Pollut. 2018 Apr;235:453-461. doi: 10.1016/j.envpol.2017.12.107. Epub 2018 Jan 6.
PubMed 29310089Kataria A, Trasande L, Trachtman H. The effects of environmental chemicals on renal function. Nat Rev Nephrol. 2015 Oct;11(10):610-25. doi: 10.1038/nrneph.2015.94. Epub 2015 Jun 23.
PubMed 26100504Mengozzi A, Carli F, Biancalana E, Della Latta V, Seghieri M, Gastaldelli A, Solini A. Phthalates Exposure as Determinant of Albuminuria in Subjects With Type 2 Diabetes: A Cross-Sectional Study. J Clin Endocrinol Metab. 2019 May 1;104(5):1491-1499. doi: 10.1210/jc.2018-01797.
PubMed 30462244
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploring the Association Between Phthalates Exposure, Measured Through Their Urinary Metabolites, and Renal Function Impairment in Individuals With TYpe 2 Diabetes - Protocol 2
- ClinicalTrials.gov ID
- NCT03622957
- Acronym / sponsor ID
- PURITY-2 / PURITY - Protocol 2
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University of PisaUniversity, hospital or other
- Collaborators
- Istituto di Fisiologia Clinica CNR
- Study start
- 10 Aug 2018 (estimated)
- Primary completion
- 3 Sep 2018 (estimated)
- Study completion
- 3 Sep 2018 (estimated)
- First posted
- 9 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Type 2 diabetes subjects | – | –Type 2 diabetes subjects consecutively referring to Santa Chiara, Pisa diabetes outpatients clinic |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Type 2 diabetes individuals referring to our outpatient clinics
Key inclusion criteria (1 listed)
- Age 18-85 years, T2D diagnosis, T2D duration >6 months,
Key exclusion criteria (1 listed)
- occurring acute clinical conditions, eGFR <15 ml/min/1.73m2, BMI > 40 Kg/m2.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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].
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).
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.
1 secondary outcome
CV Events (Yes/No)
Time frame: Single routine clinical visit
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2018.
- Background: PubMed 25249672Tuttle KR, Bakris GL, Bilous RW, Chiang JL, de Boer IH, Goldstein-Fuchs J, Hirsch IB, Kalantar-Zadeh K, Narva AS, Navaneethan SD, Neumiller JJ, Patel UD, Ratner RE, Whaley-Connell AT, Molitch ME. Diabetic kidney disease: a report from an ADA Consensus Conference. Diabetes Care. 2014 Oct;37(10):2864-83. doi: 10.2337/dc14-1296.
- Background: PubMed 29247554Winocour PH. Diabetes and chronic kidney disease: an increasingly common multi-morbid disease in need of a paradigm shift in care. Diabet Med. 2018 Mar;35(3):300-305. doi: 10.1111/dme.13564. Epub 2018 Jan 8.
- Background: PubMed 14998748Kato K, Silva MJ, Reidy JA, Hurtz D 3rd, Malek NA, Needham LL, Nakazawa H, Barr DB, Calafat AM. Mono(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-oxohexyl) phthalate as biomarkers for human exposure assessment to di-(2-ethylhexyl) phthalate. Environ Health Perspect. 2004 Mar;112(3):327-30. doi: 10.1289/ehp.6663.
- Background: PubMed 23429708Braun JM, Sathyanarayana S, Hauser R. Phthalate exposure and children's health. Curr Opin Pediatr. 2013 Apr;25(2):247-54. doi: 10.1097/MOP.0b013e32835e1eb6.
- Background: PubMed 28587233Dong R, Zhao S, Zhang H, Chen J, Zhang M, Wang M, Wu M, Li S, Chen B. Sex Differences in the Association of Urinary Concentrations of Phthalates Metabolites with Self-Reported Diabetes and Cardiovascular Diseases in Shanghai Adults. Int J Environ Res Public Health. 2017 Jun 5;14(6):598. doi: 10.3390/ijerph14060598.
- Background: PubMed 28898934Dales RE, Kauri LM, Cakmak S. The associations between phthalate exposure and insulin resistance, beta-cell function and blood glucose control in a population-based sample. Sci Total Environ. 2018 Jan 15;612:1287-1292. doi: 10.1016/j.scitotenv.2017.09.009. Epub 2017 Sep 8.
- Background: PubMed 24178978Trasande L, Sathyanarayana S, Trachtman H. Dietary phthalates and low-grade albuminuria in US children and adolescents. Clin J Am Soc Nephrol. 2014 Jan;9(1):100-9. doi: 10.2215/CJN.04570413. Epub 2013 Oct 31.
- Background: PubMed 29310089Wu CF, Hsiung CA, Tsai HJ, Tsai YC, Hsieh HM, Chen BH, Wu MT. Interaction of melamine and di-(2-ethylhexyl) phthalate exposure on markers of early renal damage in children: The 2011 Taiwan food scandal. Environ Pollut. 2018 Apr;235:453-461. doi: 10.1016/j.envpol.2017.12.107. Epub 2018 Jan 6.
- Background: PubMed 26100504Kataria A, Trasande L, Trachtman H. The effects of environmental chemicals on renal function. Nat Rev Nephrol. 2015 Oct;11(10):610-25. doi: 10.1038/nrneph.2015.94. Epub 2015 Jun 23.
- Derived from this study: PubMed 30462244Mengozzi A, Carli F, Biancalana E, Della Latta V, Seghieri M, Gastaldelli A, Solini A. Phthalates Exposure as Determinant of Albuminuria in Subjects With Type 2 Diabetes: A Cross-Sectional Study. J Clin Endocrinol Metab. 2019 May 1;104(5):1491-1499. doi: 10.1210/jc.2018-01797.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes Mellitus, Type 2 and Albuminuria, run by University of Pisa at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anna Solini, Associate Professor, MD, PhD (+39 050993482, anna.solini@med.unipi), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phthalates exposure [ug/g] (time frame: Single routine clinical visit). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03622957, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2018.