Role of Epoxyeicosatrienoic Acids in Chronic Allograft Nephropathy - The TRANSPLANT-EETs Study

Kidney Transplant Recipients Clinical Trial

— TRANSPLANTEETs  

Official title:

Role of Epoxyeicosatrienoic Acids in Chronic Allograft Nephropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02555566
• Other study ID #: 2013/150/HP
• Status: Completed
• Phase: N/A
• First received: September 17, 2015
• Last updated: December 6, 2016
• Start date: March 2014
• Est. completion date: December 2016

Study information

• Verified date: December 2016
• Source: University Hospital, Rouen
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

Endothelial lesions within the transplanted kidney are a major determinant of chronic allograft nephropathy. Epoxyeicosatrienoic acids (EETs) are endothelium-derived hyperpolarizing factors with anti-inflammatory, antiproliferative and vasodilator properties.

The main goal of the investigators' study is to evaluate whether genetic polymorphisms of specific enzymes responsible for the bioavailability of EETs are associated with post-transplant kidney function.

To this end, 80 kidney transplant recipients will be included. Prespecified genetic polymorphisms of CYP 2J2, CYP 2C8, CYP 2C9, CYP 2C9, CYP 2C19 and EPHX2 will be determined. Kidney function will be recorded 3, 6, 12 and 36 months after transplantation. Flow-mediated dilatation, EETs and circulating biomarkers of endothelial function will be measured in the radial artery.

The expected results of this study to provide preliminary evidence supporting a beneficial role of an increase in the bioavailability of EETs in kidney transplant recipients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patient aged 18 to 75 yo

• Caucasian (because of different CYP epoxygenase polymorphisms)

• First kidney transplantation performed in Rouen University Hospital after 2000, and at least 12 months before inclusion

• Patient having read, understood and approved the informed consent

• Efficient contraception in child-bearing aged women

• Regular health insurance

Exclusion Criteria:

• Primary non-function, or allograft loss before 1 year

• Previous kidney transplantation

• History of psychiatric, psychologic or sensorial disorder preventing the patient from correctly understanding the protocol

• History of bilateral arm or forearm arteriovenous fistula

• Counter-indication to trinitrin

• Insufficient understanding of written or spoken French language

• Liberty-deprived patient

• Pregnancy or absence of contraception in child-bearing aged women

• Patient enrolled in another research protocol within 2 weeks before inclusion

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Kidney Transplant Recipients

Intervention

Procedure:
• Blood sampling
Blood sampling is done for Kidney transplant recipients for evaluation of the polymorphisms and EETs dosage
• flow-mediated distal stimulation of the forearm radial artery by cutaneous heating
Flow-mediated distal stimulation of the forearm radial artery by cutaneous heating for Kidney transplant recipients

Locations

Country	Name	City	State
France	Rouen University Hospital	Rouen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Rouen

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference between patients with the EPHX2 Lys55Arg polymorphism and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	12 Months after transplantation	No
Secondary	Difference between patients with the EPHX2 Lys55Arg polymorphism and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	3 Months after transplantation	No
Secondary	Difference between patients with the EPHX2 Lys55Arg polymorphism and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	6 Months after transplantation	No
Secondary	Difference between patients with the EPHX2 Lys55Arg polymorphism and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	36 Months after transplantation	No
Secondary	Difference between patients with specified polymorphisms and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	3 Months after transplantation	No
Secondary	Difference between patients with specified polymorphisms and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	6 Months after transplantation	No
Secondary	Difference between patients with specified polymorphisms and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	12 Months after transplantation	No
Secondary	Difference between patients with specified polymorphisms and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	36 Months after transplantation	No
Secondary	Difference between blood EETs concentration at baseline and after distal cutaneous heating for patients with the specified polymorphisms.	EEts plasma concentration is measured using liquid chromatography coupled to tandem mass spectrometry before and after distal cutaneous heating. Unit is ng per mL	Day 1	No
Secondary	Difference between blood EETs concentration at baseline and after distal cutaneous heating for patients without the specified polymorphisms.	EEts plasma concentration is measured using liquid chromatography coupled to tandem mass spectrometry before and after distal cutaneous heating. Unit is ng per mL	Day 1	No
Secondary	Difference between variation of diameter of the forearm radial artery after distal cutaneous heating for patients with the specified polymorphisms.	Variation of diameter of the radial artery is measured in millimeter.	Day 1	No
Secondary	Difference between variation of diameter of the forearm radial artery after distal cutaneous heating for patients without the specified polymorphisms.	Variation of diameter of the radial artery is measured in millimeter.	Day 1	No