ACE-inhibitors in Extracapillary Glomerulonephritis

Phase 2

• Conditions: Extracapillary Glomerulonephritis
• Interventions: Drug: Lisinopril

• Registration Number: NCT02682459
• Lead Sponsor: Monia Lorini

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-02
• Study First Submitted: 2016-02-10
• Study First Submitted QC: 2016-02-12
• Study First Posted: 2016-02-15
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-05
• Last Update Posted: 2018-04-06
• Primary Completion: 2019-09
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 22

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lisinopril	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	Changes from baseline and 6 and 18 month.
Glomerular Filtration Rate (GFR) measured by iohexol plasma clearance	Changes from baseline and 6, 12 and 18 month.
Number of fibrosclerotic crescents	Changes from baseline and 6 and 18 month.

Trial Locations

Locations (2)

ASST Papa Giovanni XXIII; 🇮🇹 Bergamo, Italy

Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò; 🇮🇹 Ranica, Bergamo, Italy