search
Back to results

ACE-inhibitors in Extracapillary Glomerulonephritis (EXTRA)

Primary Purpose

Extracapillary Glomerulonephritis

Status
Unknown status
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Lisinopril
Sponsored by
Monia Lorini
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Extracapillary Glomerulonephritis focused on measuring Extracapillary glomerulonephritis, crescentic glomerulonephritis, rapidly progressive renal failure, chronic kidney disease, ACE-inhibitors, fibrosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele DaccòRecruiting
  • ASST Papa Giovanni XXIIIRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Lisinopril

No intervention

Arm Description

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.

Patients will receive only the standard immunosuppressive therapy.

Outcomes

Primary Outcome Measures

The extent of extracapillary proliferation on light microscopy, measured as % of total glomeruli with proliferative lesions at post-treatment repeat biopsy.

Secondary Outcome Measures

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
Number of fibrosclerotic crescents
Glomerular Filtration Rate (GFR) measured by iohexol plasma clearance

Full Information

First Posted
February 10, 2016
Last Updated
April 5, 2018
Sponsor
Monia Lorini
Collaborators
Istituto Di Ricerche Farmacologiche Mario Negri
search

1. Study Identification

Unique Protocol Identification Number
NCT02682459
Brief Title
ACE-inhibitors in Extracapillary Glomerulonephritis
Acronym
EXTRA
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Unknown status
Study Start Date
February 2016 (undefined)
Primary Completion Date
September 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Monia Lorini
Collaborators
Istituto Di Ricerche Farmacologiche Mario Negri

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Extracapillary Glomerulonephritis
Keywords
Extracapillary glomerulonephritis, crescentic glomerulonephritis, rapidly progressive renal failure, chronic kidney disease, ACE-inhibitors, fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
22 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Lisinopril
Arm Type
Experimental
Arm Description
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.
Arm Title
No intervention
Arm Type
No Intervention
Arm Description
Patients will receive only the standard immunosuppressive therapy.
Intervention Type
Drug
Intervention Name(s)
Lisinopril
Primary Outcome Measure Information:
Title
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.
Secondary Outcome Measure Information:
Title
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.
Title
Number of fibrosclerotic crescents
Time Frame
Changes from baseline and 6 and 18 month.
Title
Glomerular Filtration Rate (GFR) measured by iohexol plasma clearance
Time Frame
Changes from baseline and 6, 12 and 18 month.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: Type I: Anti-Glomerular Basement Membrane (GBM) antibody glomerulonephritis, Type II: Pauci-immune vasculitis or Anti Neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis; 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Barbara Ruggiero, MD
Phone
0039 035 45351
Email
barbara.ruggiero@marionegri.it
First Name & Middle Initial & Last Name or Official Title & Degree
Ettore Sabadini, MD
Email
esabadini@asst-pg23.it
Facility Information:
Facility Name
Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò
City
Ranica
State/Province
Bergamo
ZIP/Postal Code
24020
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Barbara Ruggiero, MD
Facility Name
ASST Papa Giovanni XXIII
City
Bergamo
ZIP/Postal Code
24147
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giuseppe Remuzzi, MD
First Name & Middle Initial & Last Name & Degree
Ettore Sabadini, MD
First Name & Middle Initial & Last Name & Degree
Piero Ruggenenti, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24578468
Citation
Hruskova Z, Honsova E, Berden AE, Rychlik I, Lanska V, Zabka J, Bajema IM, Tesar V. Repeat protocol renal biopsy in ANCA-associated renal vasculitis. Nephrol Dial Transplant. 2014 Sep;29(9):1728-32. doi: 10.1093/ndt/gfu042. Epub 2014 Feb 26.
Results Reference
background
PubMed Identifier
19875807
Citation
Smeets B, Angelotti ML, Rizzo P, Dijkman H, Lazzeri E, Mooren F, Ballerini L, Parente E, Sagrinati C, Mazzinghi B, Ronconi E, Becherucci F, Benigni A, Steenbergen E, Lasagni L, Remuzzi G, Wetzels J, Romagnani P. Renal progenitor cells contribute to hyperplastic lesions of podocytopathies and crescentic glomerulonephritis. J Am Soc Nephrol. 2009 Dec;20(12):2593-603. doi: 10.1681/ASN.2009020132. Epub 2009 Oct 29.
Results Reference
background
PubMed Identifier
21718676
Citation
Benigni A, Morigi M, Rizzo P, Gagliardini E, Rota C, Abbate M, Ghezzi S, Remuzzi A, Remuzzi G. Inhibiting angiotensin-converting enzyme promotes renal repair by limiting progenitor cell proliferation and restoring the glomerular architecture. Am J Pathol. 2011 Aug;179(2):628-38. doi: 10.1016/j.ajpath.2011.04.003. Epub 2011 Jun 2.
Results Reference
background

Learn more about this trial

ACE-inhibitors in Extracapillary Glomerulonephritis

We'll reach out to this number within 24 hrs