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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04769778
Recruitment Status : Recruiting
First Posted : February 25, 2021
Last Update Posted : May 19, 2021
Sponsor:
Information provided by (Responsible Party):
Josep M Cruzado, Hospital Universitari de Bellvitge

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.

Condition or disease Intervention/treatment Phase
Chronic Kidney Allograft Nephropathy Drug: Valsartan 80Mg Oral Tablet Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Treatment with valsartan versus no treatment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Renin Angiotensin System Blockade in Renal Transplant Patients With Presence of PECs in Urine
Actual Study Start Date : February 19, 2020
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2023


Arm Intervention/treatment
Experimental: Valsartan
Treatment with valsartan
Drug: Valsartan 80Mg Oral Tablet
treatment with 80mg /day of valsartan

No Intervention: no treatment
no treatment received



Primary Outcome Measures :
  1. prevention of fall of glomerular filtration rate [ Time Frame: 12 months ]
    To assess whether treatment with an angiotensin II receptor antagonist (AIIRA) prevents the fall of glomerular filtration in the subgroup of kidney transplant patients with presence of PECs in urine.


Secondary Outcome Measures :
  1. SN-GFR [ Time Frame: 12 months ]
    Compare the SN-GFR (nephron glomerular filtration rate)

  2. Single cell RNA sequencing [ Time Frame: 12 months ]
    Carry out single cell RNA sequencing studies using cell microdissection techniques of PEC cells isolated from renal biopsies performed at 6 and 24 m after transplantation in patients without uPECs and in patients with uPECs included in the therapeutic intervention study. These studies will allow us to know the changes of gene expression in PECS cells that can be associated with the favorable response in treated or untreated patients.

  3. podocyturia [ Time Frame: 12 months ]
    To determine the influence of the treatment on podocyturia and the preservation of the number of podocytes at 2 years post transplant.

  4. graft survival [ Time Frame: 12 months ]
    Evaluate the influence of treatment on graft survival

  5. patient survival [ Time Frame: 12 months ]
    Evaluate the influence of treatment on patient survival and proteinuria.

  6. Chronic Glomerular Lessions [ Time Frame: 12 months ]
    Evaluate the influence of treatment on number of participants with chronic glomerular lesions.

  7. Suspected Unexpected Serious Adverse Reaction (SUSAR) reporting unexpected serious adverse reactions) [ Time Frame: 12 months ]
    Evaluate the safety of the treatment on the number of patients with Suspected Unexpected Serious Adverse Reaction (SUSAR) reporting unexpected serious adverse reactions) unexpected adverse reactions) and rate of treatment discontinuations.

  8. Proteinuria [ Time Frame: 12 months ]
    Evaluate the influence of treatment on measure of proteinuria



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04769778


Contacts
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Contact: JOSEP M CRUZADO, MD, PhD 932607385 jmcruzado@bellvitgehospital.cat
Contact: Carolina Polo, PhD +34 93 260 73 85 cpolo@idibell.com

Locations
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Spain
Nephrology Department. Hospital Universitari de Bellvitge Recruiting
L'Hospitalet de Llobregat, Barcelona, Spain, 08907
Contact: Josep M Cruzado, Medical Doctor    0034932607602    27541jcg@comb.es   
Contact: CAROLINA POLO, PhD    932607385    cpolo@idibell.cat   
Sponsors and Collaborators
Josep M Cruzado
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Responsible Party: Josep M Cruzado, Head of Nephrology, Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier: NCT04769778    
Other Study ID Numbers: PRONE
First Posted: February 25, 2021    Key Record Dates
Last Update Posted: May 19, 2021
Last Verified: May 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Josep M Cruzado, Hospital Universitari de Bellvitge:
renin angiotensin
kidney transplant
PEC's
Additional relevant MeSH terms:
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Kidney Diseases
Urologic Diseases
Valsartan
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action