- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02682459
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
Conditions
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
- Name: Barbara Ruggiero, MD
- Phone Number: 0039 035 45351
- Email: barbara.ruggiero@marionegri.it
Study Contact Backup
- Name: Ettore Sabadini, MD
- Email: esabadini@asst-pg23.it
Study Locations
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Bergamo, Italy, 24147
- Recruiting
- ASST Papa Giovanni XXIII
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Principal Investigator:
- Giuseppe Remuzzi, MD
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Sub-Investigator:
- Ettore Sabadini, MD
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Sub-Investigator:
- Piero Ruggenenti, MD
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Bergamo
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Ranica, Bergamo, Italy, 24020
- Recruiting
- Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò
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Sub-Investigator:
- Barbara Ruggiero, MD
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-
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:
- 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.
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.
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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.
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Changes from baseline and 6 and 18 month.
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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.
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Number of fibrosclerotic crescents
Time Frame: Changes from baseline and 6 and 18 month.
|
Changes from baseline and 6 and 18 month.
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Glomerular Filtration Rate (GFR) measured by iohexol plasma clearance
Time Frame: Changes from baseline and 6, 12 and 18 month.
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Changes from baseline and 6, 12 and 18 month.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
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.
General Publications
- 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.
- 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.
- 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.
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
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- EXTRA
- 2015-003884-12 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
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.
Clinical Trials on Extracapillary Glomerulonephritis
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Celldex TherapeuticsTerminatedC3 Glomerulonephritis | Dense Deposit Disease | Membranoproliferative Glomerulonephritis Type IIUnited States
-
Alexion PharmaceuticalsAchillion, a wholly owned subsidiary of AlexionCompletedC3 Glomerulopathy | C3 Glomerulonephritis | Dense Deposit Disease | Immune Complex Mediated Membranoproliferative Glomerulonephritis | Membranoproliferative Glomerulonephritis Types I, II, and IIINetherlands, Australia, Belgium
-
Mario Negri Institute for Pharmacological ResearchAlexion PharmaceuticalsCompletedIC-MPGN | C3 Glomerulopathy | C3 Glomerulonephritis | Dense Deposit Disease | Immune Complex Membranoproliferative GlomerulonephritisItaly
-
University Magna GraeciaCompletedIGA GlomerulonephritisItaly
-
Assiut UniversityUnknownMembranoproliferative Glomerulonephritis
-
Apellis Pharmaceuticals, Inc.Active, not recruitingC3G | IC-MPGN | C3 Glomerulopathy | C3 Glomerulonephritis | Complement 3 Glomerulopathy | Complement 3 Glomerulopathy (C3G) | Complement 3 Glomerulonephritis | Dense Deposit Disease | DDD | Membranoproliferative Glomerulonephritis | Membranoproliferative Glomerulonephritis (MPGN) | Immune Complex Membranoproliferative...United States, Spain, France, Germany, United Kingdom, Netherlands, Brazil, Israel, Japan, Australia, Austria, Italy, Switzerland, Korea, Republic of, Czechia, Belgium, Argentina, Canada, Poland
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Apellis Pharmaceuticals, Inc.Active, not recruitingC3G | IC-MPGN | C3 Glomerulopathy | C3 Glomerulonephritis | Complement 3 Glomerulopathy | Complement 3 Glomerulopathy (C3G) | Complement 3 Glomerulonephritis | Dense Deposit Disease | DDD | Membranoproliferative Glomerulonephritis | Membranoproliferative Glomerulonephritis (MPGN) | Immune Complex Membranoproliferative...United States, Australia, Brazil, Czechia, France, Italy, Korea, Republic of, Netherlands, Spain, Switzerland, United Kingdom
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Apellis Pharmaceuticals, Inc.AvailableC3G | IC-MPGN | C3 Glomerulopathy | C3 Glomerulonephritis | Complement 3 Glomerulopathy | Complement 3 Glomerulopathy (C3G) | Complement 3 Glomerulonephritis | Dense Deposit Disease | DDD | Membranoproliferative Glomerulonephritis | Membranoproliferative Glomerulonephritis (MPGN) | Immune Complex Membranoproliferative...United States
-
Mayo ClinicCompletedGlomerulonephritis, MembranoproliferativeUnited States
-
AlexionTerminatedIC-MPGN | C3 Glomerulopathy | C3 Glomerulonephritis | Dense Deposit Disease | Immune Complex Membranoproliferative GlomerulonephritisUnited States, Australia, Belgium, Italy, Netherlands
Clinical Trials on Lisinopril
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SandozCompleted
-
The Affiliated Hospital of Qingdao UniversityCompleted
-
IPCA Laboratories Ltd.Completed
-
IPCA Laboratories Ltd.Completed
-
SandozCompleted
-
IPCA Laboratories Ltd.Completed
-
IPCA Laboratories Ltd.Completed
-
Par Pharmaceutical, Inc.PharmaKinetics Laboratories Inc.Completed
-
Hoffmann-La RocheCompletedDiabetes Mellitus Type 2United States
-
NovartisTerminatedHypertension | Early Diabetic NephropathySwitzerland