Hydroxychloroquine Sulfate for Reduction of Proteinuria in Patients With IgA Nephropathy: a Self- Controlled Study

Primary IgA Nephropathy Clinical Trial

Official title:

Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02351752
• Other study ID #: 2014?851?
• Status: Completed
• Phase: Phase 4
• First received: January 27, 2015
• Last updated: December 15, 2015
• Start date: January 2015
• Est. completion date: October 2015

Study information

• Verified date: December 2015
• Source: Peking University First Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

IgA nephropathy is the most common type of primary glomerulonephritis and might caused by deposition of immune complex containing IgA in mesangium and causing local immune activation. Hydroxychloroquine reduces the activation of dendritic cells and the inflammatory process and showed the potential effect of treatment of patients with IgA nephropathy.

The investigators study will recruite 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 300-400mg/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.

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, protienuria, 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 nephrits. 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.

Our study will recruite 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 300-400mg/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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. primary IgA nephopathy

2. age 18-75 years

3. proteinuria range from 0.75 to 3.5g/d even after three-month treatment by sufficient ACEi/ARB

4. eGFR>30ml/min/1.73m2

Exclusion Criteria:

1. immune suppressive agent in recent one years

2. crescent glomerulonephritis, might use immune suppressive agent

3. chronic hepatic disease

4. myocardial infarction

5. malignant hypertension

6. stroke

7. malignant tumor

8. retinopathy

9. other contraindication of Hydroxychloroquine

10. pregnancy and breastfeeding women

11. life expectancy for less than 6 months

12. in other clinical trials

13. not suitable for the study judged by investigator

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• Kidney Diseases
• Primary IgA Nephropathy

Intervention

Drug:
• Hydroxychloroquine Sulfate
Hydroxychloroquine Sulfate: 0.1 Tid(eGFR 30-59);0.2 Bid (eGFR>60)

Locations

Country	Name	City	State
China	Peking University First Hospital	BeiJing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
LLiu

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	proteinuia		total four months(proteinic will recorded every 2 months )	No