Hydroxychloroquine Sulfate Alleviates Persistent Proteinuria in IgA Nephropathy

NCT ID: NCT02765594

Last Updated: 2017-09-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2019-06-30

Brief Summary

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.

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.

Conditions

Primary IgA Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

valsartan only:control group

valsartan (160mg/d)

Group Type: EXPERIMENTAL

Valsartan

Intervention Type: DRUG

160mg qd

hydroxychloroquine with valsartan:study group

valsartan (160mg/d) and Hydroxychloroquine Sulfate ( 400mg/d, twice daily)

Group Type: EXPERIMENTAL

Hydroxychloroquine Sulfate

Intervention Type: DRUG

200mg bid

Valsartan

Intervention Type: DRUG

160mg qd

Interventions

Hydroxychloroquine Sulfate

200mg bid

Intervention Type: DRUG

Valsartan

160mg qd

Intervention Type: DRUG

Other Intervention Names

Fenle; Diovan

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

RUITONG GAO, MD

Role: STUDY_DIRECTOR

Peking Union Medical College Hospital

Locations

Peing Union Medical College Hospital

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

RUITONG GAO, MD

Role: CONTACT

gaoruitong@gmail.com

86-010-69155058

Facility Contacts

Ruitong Gao, MD

Role: primary

gaoruitong@gmail.com

86-010-69155058

References

Tunnicliffe DJ, Reid S, Craig JC, Samuels JA, Molony DA, Strippoli GF. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev. 2024 Feb 1;2(2):CD003962. doi: 10.1002/14651858.CD003962.pub3.

Reference Type: DERIVED

PMID: 38299639 (View on PubMed)

Other Identifiers

PUMCHHCQIgAN01

Identifier Type: -

Identifier Source: org_study_id