A Study of Hydroxychloroquine Sulfate for Reduction of Proteinuria in Patients With IgA Nephropathy

Phase 2

Completed

• Conditions: Hydroxychloroquine; IgA Patients
• Interventions: Drug: Placebo; Drug: Hydroxychloroquine Sulfate

• Registration Number: NCT02942381
• Lead Sponsor: Peking University First Hospital

Brief Summary

The investigators study will recruit IgA nephropathy patients with proteinuria range from 0.75 to 3.5g/d even after three-month treatment by sufficient ACEi/ARB. The patients were treated with Hydroxychloroquine 200-400mg/d according to eGFR. The proteinuria will recorded every two months and total four months. Then, the drug will be stopped for two months for observation of change of proteinuria.

Detailed Description

Immunoglobulin A (IgA) nephropathy is the most common type of primary glomerulonephritis worldwide. Several studies indicated that 6-43% of IgA nephropathy patients would develop end-stage kidney disease (ESKD) over a period of 10 years. The clinical risk factors for progression are hypertension, proteinuria, impaired renal function and histologic lesions at presentation. There is no well accepted optimal therapy for patients with IgA. Current established therapies include full RAS inhibition and optimal blood pressure control for patients with proteinuria and/or hypertension.

Hydroxychloroquine has been used for many years to treat malaria. It is also used to treat systemic lupus erythematosus, rheumatic disorders like rheumatoid arthritis and Sjögren's Syndrome. Recently, several studies found that Hydroxychloroquine could reduce the risk of ESRD in patients with lupus nephritis. The mechanism of the treatment wasn't well known so far. Some investigators found that Hydroxychloroquine increases lysosomal pH in antigen presenting cells. In inflammatory conditions, it blocks toll-like receptors on plasmacytoid dendritic cells (PDCs). Toll-like receptor 9 (TLR 9), which recognizes DNA-containing immune complexes, leads to the production of interferon and causes the dendritic cells to mature and present antigen to T cells. Hydroxychloroquine, by decreasing TLR signaling, reduces the activation of dendritic cells and the inflammatory process.

The pathogenesis of IgA nephropathy included the deposition of immune complex containing IgA in mesangium and causing local immune activation and injury to kidney. Therefore, Hydroxychloroquine might have the potential effect of anti-inflammation in patients with IgA nephropathy, reduced the proteinuria and had the renal protect effect.

The investigators study will recruit IgA nephropathy patients with proteinuria range from 0.75 to 3.5g/d even after three-month treatment by sufficient ACEi/ARB. The patients were treated with Hydroxychloroquine 200-400mg/d according to eGFR. The proteinuria will recorded every two months and total four months. Then, the drug will be stopped for two months for observation of change of proteinuria.

Study Timeline

• Study Start: 2016-09-13
• Study First Submitted: 2016-10-14
• Study First Submitted QC: 2016-10-21
• Study First Posted: 2016-10-24
• Primary Completion: 2018-01-08
• Study Completion: 2018-01-08
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-02
• Last Update Posted: 2018-02-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• primary IgA nephropathy
• age 18-75 years
• proteinuria range from 0.75 to 3.5g/d even after three-month treatment by sufficient ACEi/ARB
• eGFR>30ml/min/1.73m2

Exclusion Criteria

• immune suppressive agent in recent one years
• crescent glomerulonephritis, might use immune suppressive agent
• chronic hepatic disease
• myocardial infarction
• malignant hypertension
• stroke
• malignant tumor
• retinopathy
• other contraindication of Hydroxychloroquine
• pregnancy and breastfeeding women
• life expectancy for less than 6 months
• in other clinical trials
• not suitable for the study judged by investigator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo and supportive treatment
Hydroxychloroquine Sulfate	Hydroxychloroquine Sulfate	200mg Bid (eGFR\>60 ml/min/1.73m2), 100mg Tid (eGFR45-59 ml/min/1.73m2), 100mg Bid (eGFR 30-44 ml/min/1.73m2) and supportive treatment

Primary Outcome Measures

Name	Time	Method
Proteinuria （g/d）	every two months(total six months)

Secondary Outcome Measures

Name	Time	Method
Albuminuria and creatinine ratio(mg/g)	every two months(total six months)

Trial Locations

Locations (1)

Peking University First Hospital; 🇨🇳 BeiJing, Beijing, China