Renin Angiotensin System Blockade in Renal Transplant Patients With Presence of PECs in Urine

NCT ID: NCT04769778

Last Updated: 2021-05-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-19
• Study Completion Date: 2023-06-30

Brief Summary

By means of a personalized medicine strategy, investigators are going to evaluate if the treatment with an angiotensin II receptor antagonist (ARAII) in renal transplant patients with the presence of renal progenitor cells (PECs) in the urine is able to prevent the expected loss of glomerular filtration (GFR) observed in this subgroup of patients. In addition, investigators intend to deepen the mechanisms of glomerular damage and glomerular repair involved in the process of chronic allograft damage.

Detailed Description

A randomized, double-blind clinical trial will be performed in renal transplant patients in month 6 post-transplant, at the time of protocol renal biopsy. After verifying the inclusion and exclusion criteria, informed consent will be obtained. Patients with urinary PECs will be randomized to 80 mg of valsartan vs. placebo (sample size calculated for a superiority study, 45 patients per group). Patients without PECs in urine will be followed according to usual clinical practice. The follow-up will be up to 2 years post-transplant. At baseline (6 m post-transplant) and at 2 years the GFR will be measured by means of iohexol clearance (main variable) and, in addition, we will analyze safety variables such as patient and graft survival and RAGIs. By means of morphometry techniques on renal biopsy and by measuring the renal cortical volume by high resolution CT, the number of glomeruli will be determined, which in turn, will allow to calculate the SN-GFR. Finally, in 5 patients per study group and in 5 controls, PECs of renal tissue will be isolated by means of laser microdissection techniques to perform single-cell RNA sequencing techniques to assess the molecular pathways involved in the glomerular damage and repair process and how the RAAS blockade modifies such molecular pathways.

Conditions

Chronic Kidney Allograft Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Valsartan

Treatment with valsartan

Group Type: EXPERIMENTAL

Valsartan 80Mg Oral Tablet

Intervention Type: DRUG

treatment with 80mg /day of valsartan

no treatment

no treatment received

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Valsartan 80Mg Oral Tablet

treatment with 80mg /day of valsartan

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Written informed consent
• Stable renal function understood as a variation of eGFR of less than 15% in the last 3 months
• Immunosuppression maintenance based on tacrolimus and MMF / MPA

Exclusion Criteria

• Chronic active infection by HCV, HBV, HIV.
• Treatment with inhibitors of the renin angiotensin system.
• Double kidney transplant or combined with another organ.
• Immunosuppression of maintenance other than tacrolimus and MMF / MPA.
• eGFR <20 ml / min / 1.73m2.
• History of allergy or intolerance to inhibitors of the renin angiotensin system.
• Physically fertile women who plan to become pregnant, are pregnant and

/ or breast-feeding, or who do not want to use effective contraception during their participation in the study.

• Any other medical condition that, in the opinion of the investigator, based on the counting or review of clinical records, could affect the completion of the study, including, but not limited to, visual problems or cognitive impairment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Josep M Cruzado

OTHER

Sponsor Role: lead

Responsible Party

Josep M Cruzado

Head of Nephrology

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Nephrology Department. Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

JOSEP M CRUZADO, MD, PhD

Role: CONTACT

jmcruzado@bellvitgehospital.cat

932607385

Carolina Polo, PhD

Role: CONTACT

cpolo@idibell.com

+34 93 260 73 85

Facility Contacts

Josep M Cruzado, Medical Doctor

Role: primary

27541jcg@comb.es

0034932607602

CAROLINA POLO, PhD

Role: backup

cpolo@idibell.cat

932607385

Other Identifiers

PRONE

Identifier Type: -

Identifier Source: org_study_id