Hydroxychloroquine Sulfate Alleviates Persistent Proteinuria in IgA Nephropathy (HCQIgAN)

September 19, 2017 updated by: Peking Union Medical College Hospital

Hydroxychloroquine Sulfate Alleviates Persistent Proteinuria in IgA Nephropathy:a Single Center Prospective Randomized Controlled Study

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in the world.There is to date no curative therapy for patients with IgAN.It is considered that dendritic cells, Toll-like receptor (TLR) 9 and cytokines interleukin-6 (IL-6), and interferon-alpha (IFN-a) and tumor necrosis factor-alpha (TNF-α), play an important role in the aberrant mucosal response. Hydroxychloroquine is an antimalarial agent and had a notable impact on immune activation by the reduction of circulating activated immune cells that including decreased TLR-expressing cells, reduced IFN-secreting plasmacytoid dendritic cells, reduced production of inflammatory cytokines including interferon alpha, IL-6 and TNF alpha. Recent studies showed hydroxychloroquine had a benefit for renal remission and could retard the onset of renal damage in patients with lupus nephritis. hydroxychloroquine may have the potential effect in IgA nephropathy, alleviated the proteinuria and had the renal protect effect. This will be a single center, prospective, randomized, controlled study to assess the utility of hydroxychloroquine in IgAN patients.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in the world. Its estimated frequency is at least 2.5 cases per year per 100,000 adults. The glomerulopathy usually progressed slowly leading to end stage renal disease (ESRD). ESRD developed in 20%-40% of patients after 20 years. Given its complex and as yet incompletely understood pathogenetic mechanisms, there is to date no curative therapy for patients with IgAN.

Although pathogenesis of IgAN is still obscure, underglycosylated IgA-containing immune-complex including IgG or IgA antibodies against the hinge region of IgA1 are key factors for IgA nephropathy. Aberrant mucosal immune response might lead to increased production of underglycosylated IgA1. It is considered that dendritic cells, Toll-like receptor (TLR)9, and cytokines interleukin-6 (IL-6), , interferon-alpha (IFN-a) and tumor necrosis factor-alpha (TNF-α), play an important role in the aberrant mucosal response.

Hydroxychloroquine is an antimalarial agent and had a notable impact on immune activation by the reduction of circulating activated immune cells that including decreased TLR-expressing cells, reduced IFN-secreting plasmacytoid dendritic cells, reduced production of inflammatory cytokines including interferon alpha, IL-6 and TNF alpha. Recent studies showed hydroxychloroquine had a benefit for renal remission and could retard the onset of renal damage in patients with lupus nephritis.

Therefore, hydroxychloroquine, targeting dendritic cells, TLR, IL-6, IFN-α and TNF-α，may have the potential effect in IgA nephropathy, alleviated the proteinuria and had the renal protect effect. This will be a single center, prospective, randomized, controlled study to assess the utility of hydroxychloroquine added to valsartan in IgAN patients.

Study Type

Interventional

Enrollment (Anticipated)

98

Phase

  • Phase 4

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

Study Locations

  • China
      • Beijing, China, 100730
        • Recruiting
        • Peing Union Medical College Hospital
        • Contact:

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

16 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. biopsy proven primary IgA nephropathy
  2. age 18-60 years
  3. proteinuria range from 0.5 to 1.5g/d
  4. serum creatinine ≤132.6μmol/L
  5. normal blood pressure or blood pressure ≤130/80 mmHg in patients with hypertension

Exclusion Criteria:

  1. Hypersensitivity to chloroquine or to hydroxychloroquine
  2. blood pressure <90/60 mm Hg
  3. pregnancy and breastfeeding women
  4. renal artery stenosis
  5. Rapidly progressive renal insufficiency
  6. systemic lupus erythematosus or other connective tissue diseases
  7. Henoch- schoenlein purpura
  8. other nephritis
  9. diabetes mellitus
  10. retinopathy
  11. other contraindication of hydroxychloroquine
  12. severe hepatic insufficiency
  13. G6PD deficiency
  14. psoriasis or porphyria
  15. malignant hypertension
  16. viral hepatitis or other infections
  17. treatment with steroids or cytotoxic drugs during the previous three months
  18. psychiatric disorder
  19. not suitable for the study judged by investigator

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: valsartan only:control group
valsartan (160mg/d)
Drug: Valsartan
160mg qd
Other Names:
  • Diovan
Experimental: hydroxychloroquine with valsartan:study group
valsartan (160mg/d) and Hydroxychloroquine Sulfate ( 400mg/d, twice daily)
Drug: Valsartan
160mg qd
Other Names:
  • Diovan
Drug: Hydroxychloroquine Sulfate
200mg bid
Other Names:
  • Fenle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Remission (Complete [CR] or Partial [PR]) at Week 24
Time Frame: 24 weeks
CR: proteinuria <0.3 g/24 hr with no worsening of renal function (<15% estimated glomerular filtration rate(eGFR) reduction from Baseline).PR: proteinuria <3.5g/24 hrs but ≥0.3g/24 hrs and a decrease of >50% from Baseline based on 24 hours pooled urine, with no worsening of renal function(<15% eGFR reduction from Baseline). eGFR at Baseline will be defined as the Day 0 values.
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in Proteinuria Levels at the Indicated Time Points
Time Frame: Baseline and Weeks 4, 12, 24
Proteinuria is being assessed at Weeks 0, 4, 12, 24 follow-up visits. Proteinuria is based on 24 hours pooled urine. Baseline is defined as the Day 0 values. The ratio is defined as the post-Baseline value divided by the Baseline value.
Baseline and Weeks 4, 12, 24
Change from Baseline in Serum Creatinine Levels at the Indicated Time Points
Time Frame: Baseline and Weeks 4, 12, 24
Serum creatinine is being assessed at Weeks 0, 4, 12, 24 follow-up visits. Baseline is defined as the Day 0 values. The ratio is defined as the post-Baseline value divided by the Baseline value.
Baseline and Weeks 4, 12, 24
Change from Baseline in eGFR at the Indicated Time Points
Time Frame: Baseline and Weeks 4, 12, 24
eGFR is being assessed from levels of creatinine using the 4 variable version of the modification of diet in renal disease (MDRD) equation as recommended by national kidney foundation-chronic kidney disease (NKF-CKD) guidelines. eGFR is calculated at Weeks 0, 4, 12, 24 follow-up visits. Baseline is defined as the Day 0 values. The ratio is defined as the post-Baseline value divided by the Baseline value.
Baseline and Weeks 4, 12, 24
Change from Baseline in Serum IgA Levels at the Indicated Time Points
Time Frame: Baseline and Weeks 4, 12, 24
IgA levels in serum are being analyzed at Weeks 0, 4, 12, 24 follow-up visits. Baseline is defined as the Day 0 value. The ratio is defined as the post-Baseline value divided by the Baseline value.
Baseline and Weeks 4, 12, 24
Change from Baseline in Serum Interleukin-6 Levels at the Indicated Time Points
Time Frame: Baseline and Weeks 4, 12, 24
Interleukin-6 levels in serum are being analyzed at Weeks 0, 4, 12, 24 follow-up visits by means of enzyme linked immunosorbent assay (ELISA). Baseline is defined as the Day 0 value. The ratio is defined as the post-Baseline value divided by the Baseline value.
Baseline and Weeks 4, 12, 24
Change from Baseline in Serum Interferon alfa Levels at the Indicated Time Points
Time Frame: Baseline and Weeks 4, 12, 24
Interferon alfa levels in serum are being analyzed at Weeks 0, 4, 12, 24 follow-up visits by means of enzyme linked immunosorbent assay (ELISA). Baseline is defined as the Day 0 value. The ratio is defined as the post-Baseline value divided by the Baseline value.
Baseline and Weeks 4, 12, 24
Change from Baseline in Serum Tumor Necrosis Factor alpha Levels at the Indicated Time Points
Time Frame: Baseline and Weeks 4, 12, 24
Tumor necrosis factor alpha levels in serum are being analyzed at Weeks 0, 4, 12, 24 follow-up visits by means of enzyme linked immunosorbent assay (ELISA). Baseline is defined as the Day 0 value. The ratio is defined as the post-Baseline value divided by the Baseline value.
Baseline and Weeks 4, 12, 24
Adverse Effects at the Indicated Time Points
Time Frame: Weeks 4, 12, 24
Weeks 4, 12, 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Investigators

  • Study Director: RUITONG GAO, MD, Peking Union Medical College Hospital

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 (Actual)

June 1, 2016

Primary Completion (Anticipated)

May 1, 2019

Study Completion (Anticipated)

June 1, 2019

Study Registration Dates

First Submitted

April 30, 2016

First Submitted That Met QC Criteria

May 4, 2016

First Posted (Estimate)

May 6, 2016

Study Record Updates

Last Update Posted (Actual)

September 20, 2017

Last Update Submitted That Met QC Criteria

September 19, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PUMCHHCQIgAN01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

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.

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