Extracapillary GlomerulonephritisPhase 2EXTRANCT02682459
ACE-inhibitors in Extracapillary Glomerulonephritis
A Phase 2 study testing Lisinopril in people with Extracapillary Glomerulonephritis, run by Monia Lorini at 2 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extracapillary Glomerulonephritis
- What is being tested?
- Lisinopril
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 2 sitesItaly
- Study dates
- Feb 2016to Dec 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
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- 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.
Trial locations and contacts
2 sites in 1 country.
Ettore Sabadini, MD contact
Italy2 sites, 2 recruiting
- Recruiting
ASST Papa Giovanni XXIII
Bergamo, 24147
Giuseppe Remuzzi, MD
Ettore Sabadini, MD
- Recruiting
Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò
Ranica, Bergamo, 24020
Barbara Ruggiero, MD
About this study
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
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.
- Conditions
- Extracapillary Glomerulonephritis
- Being tested
- Lisinopril
- Keywords
- Extracapillary glomerulonephritis, crescentic glomerulonephritis, rapidly progressive renal failure, chronic kidney disease, ACE-inhibitors, fibrosis
- Medical subject headings
- Renal Insufficiency, Chronic, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LisinoprilDrug
| Study group | Role | What they receive |
|---|---|---|
| Lisinopril | Experimental | 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. Receives: Drug: Lisinopril |
| No intervention | No intervention | Patients will receive only the standard immunosuppressive therapy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The extent of extracapillary proliferation on light microscopy, measured as % of total glomeruli with proliferative lesions at post-treatment repeat biopsy.
Measured: Changes from baseline and 6 and 18 month.
Secondary outcomes (3)
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
Measured: Changes from baseline and 6 and 18 month.
Number of fibrosclerotic crescents
Measured: Changes from baseline and 6 and 18 month.
Glomerular Filtration Rate (GFR) measured by iohexol plasma clearance
Measured: Changes from baseline and 6, 12 and 18 month.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2016 (estimated)
- Study startFeb 2016
- Primary completionSep 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Extracapillary GlomerulonephritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Monia Lorini
- Sponsor type
- University, hospital or other
- Collaborators
- Istituto Di Ricerche Farmacologiche Mario Negri
- Responsible party
- Sponsor-investigator, Monia Lorini, A.O. Ospedale Papa Giovanni XXIII
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02682459
- Sponsor's protocol ID
- EXTRA
- Other IDs
- 2015-003884-12, 2015
- Acronym
- EXTRA
- Status last verified
- Apr 2018
- First submitted
- 10 Feb 2016
- Last updated
- 6 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
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.
PubMed 24578468Smeets 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.
PubMed 19875807Benigni 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.
PubMed 21718676
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02682459
- Acronym / sponsor ID
- EXTRA / EXTRA
- Conditions
- Extracapillary Glomerulonephritis
- Keywords
- Extracapillary glomerulonephritis, crescentic glomerulonephritis, rapidly progressive renal failure, chronic kidney disease, ACE-inhibitors, fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- Monia LoriniUniversity, hospital or other
- Collaborators
- Istituto Di Ricerche Farmacologiche Mario Negri
- Study start
- Feb 2016
- Primary completion
- Sep 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 15 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lisinopril | Experimental | Drug: LisinoprilPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- 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.
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lisinopril | Drug | Lisinopril |
Primary outcome
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.
3 secondary outcomes
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.
Number of fibrosclerotic crescents
Time frame: 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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2018.
- Background: PubMed 24578468Hruskova 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.
- Background: PubMed 19875807Smeets 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.
- Background: PubMed 21718676Benigni 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ettore Sabadini, MD contact
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lisinopril in people with Extracapillary Glomerulonephritis, run by Monia Lorini at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Barbara Ruggiero, MD (0039 035 45351, barbara.ruggiero@marionegri.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02682459, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2018.