ACE-inhibitors in Extracapillary Glomerulonephritis (EXTRA)

April 5, 2018 updated by: Monia Lorini

A Pilot, Prospective, Randomized, Open-label, Blinded Endpoint (Probe) Histopathology Trial to Assess the Effects of ACE- Inhibition Therapy on Glomerular Proliferative Lesions in Patients With Extracapillary Glomerulonephritis

The natural course of extracapillary glomerulonephritis is severe leading to End-Stage Renal Disease (ESRD) or death in most cases. Despite immunosuppressive treatment, long-term renal outcome remains poor since active crescents usually progress to fibrotic scars with glomerular occlusion and disruption.In experimental models Angiotensin Converting Enzyme (ACE)-inhibitor therapy targeting the over-expression of angiotensin type 1 (AT1) receptors, that are responsible for dysregulated proliferation of parietal cell progenitors, blocks the formation of crescents and their fibrotic evolution. Should these drugs have similar effects in humans, ACE-inhibitor therapy on top of standard immunosuppression might be instrumental to prevent ESRD and promote renal function recovery in clinical practice.

Study Overview

Status

Unknown

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

22

Phase

  • Phase 2

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

Study Contact Backup

Study Locations

      • Bergamo, Italy, 24147
        • Recruiting
        • ASST Papa Giovanni XXIII
        • Principal Investigator:
          • Giuseppe Remuzzi, MD
        • Sub-Investigator:
          • Ettore Sabadini, MD
        • Sub-Investigator:
          • Piero Ruggenenti, MD
    • Bergamo
      • Ranica, Bergamo, Italy, 24020
        • Recruiting
        • Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò
        • Sub-Investigator:
          • Barbara Ruggiero, 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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Rapidly progressive renal failure associated with acute nephritic syndrome and/or nephrotic syndrome;
  • Histology evidence of extracapillary proliferation with less than 50% of sclerotic glomeruli and associated with:

    1. Type I: Anti-Glomerular Basement Membrane (GBM) antibody glomerulonephritis,
    2. Type II: Pauci-immune vasculitis or Anti Neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis;
    3. Type III: Immune-complex mediated glomerular diseases: Proliferative lupus nephritis (LN), IgA nephropathy (IgAN)/ Schönlein-Henoch purpura, Type I membranoproliferative glomerulonephropathy (MPGN), Primary or secondary membranous nephropathy (MN), Primary or idiopathic immune complex glomerulonephritis.
  • Clinical indication to immunosuppressive therapy;
  • No specific indication to treatment with Renin Angiotensin System (RAS) inhibitors such as heart failure or coronary ischemic disease;
  • Written informed consent.

Exclusion Criteria:

  • Pre-existing advanced chronic renal failure (creatinine clearance less than 20 ml/min/1.73m2);
  • Evidence of B or C virus active infection;
  • HIV infection;
  • Recent diagnosis of malignancy;
  • Prolonged bleeding time and any other contraindication to kidney biopsy evaluation;
  • Any specific contraindication to ACE inhibitor therapy (that is: history of angioedema or other treatment-related serious adverse events);
  • Pregnancy or lactating;
  • Women of childbearing potential without following a scientifically accepted form of contraception;
  • Inability to understand the risks and benefit of the study or evidence of an uncooperative attitude;
  • Legal incapacity.

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lisinopril
Patients will receive, in addition to standard immunosuppressive therapy, lisinopril starting with 5 mg/day, then progressively up-titrated to reach the maximum tolerable dose (target dose) for 18 months.
No Intervention: No intervention
Patients will receive only the standard immunosuppressive therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The extent of extracapillary proliferation on light microscopy, measured as % of total glomeruli with proliferative lesions at post-treatment repeat biopsy.
Time Frame: Changes from baseline and 6 and 18 month.
Changes from baseline and 6 and 18 month.

Secondary Outcome Measures

Outcome Measure
Time Frame
Expression of parietal cell proliferation markers at glomerular level, graded on a scale of 0 to 3 (0: no staining, 1: mild, 2: moderate, 3: strong diffuse
Time Frame: Changes from baseline and 6 and 18 month.
Changes from baseline and 6 and 18 month.
Number of fibrosclerotic crescents
Time Frame: Changes from baseline and 6 and 18 month.
Changes from baseline and 6 and 18 month.
Glomerular Filtration Rate (GFR) measured by iohexol plasma clearance
Time Frame: Changes from baseline and 6, 12 and 18 month.
Changes from baseline and 6, 12 and 18 month.

Collaborators and Investigators

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

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.

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

February 1, 2016

Primary Completion (Anticipated)

September 1, 2019

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

February 10, 2016

First Submitted That Met QC Criteria

February 12, 2016

First Posted (Estimate)

February 15, 2016

Study Record Updates

Last Update Posted (Actual)

April 6, 2018

Last Update Submitted That Met QC Criteria

April 5, 2018

Last Verified

April 1, 2018

More Information

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.

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