Hydroxychloroquine Sulfate Alleviates Persistent Proteinuria in IgA Nephropathy

Primary IgA Nephropathy Clinical Trial

— HCQIgAN  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02765594
• Other study ID #: PUMCHHCQIgAN01
• Status: Recruiting
• Phase: Phase 4
• First received: April 30, 2016
• Last updated: September 19, 2017
• Start date: June 2016
• Est. completion date: June 2019

Study information

• Verified date: September 2017
• Source: Peking Union Medical College Hospital
• Contact: RUITONG GAO, MD
• Phone: 86-010-69155058
• Email: gaoruitong[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 98
• Est. completion date: June 2019
• Est. primary completion date: May 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• Kidney Diseases
• Primary IgA Nephropathy
• Proteinuria

Intervention

Drug:
• Hydroxychloroquine Sulfate
200mg bid
• Valsartan
160mg qd

Locations

Country	Name	City	State
China	Peing Union Medical College Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Remission (Complete [CR] or Partial [PR]) at Week 24	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	Change from Baseline in Proteinuria Levels at the Indicated Time Points	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
Secondary	Change from Baseline in Serum Creatinine Levels at the Indicated Time Points	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
Secondary	Change from Baseline in eGFR at the Indicated Time Points	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
Secondary	Change from Baseline in Serum IgA Levels at the Indicated Time Points	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
Secondary	Change from Baseline in Serum Interleukin-6 Levels at the Indicated Time Points	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
Secondary	Change from Baseline in Serum Interferon alfa Levels at the Indicated Time Points	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
Secondary	Change from Baseline in Serum Tumor Necrosis Factor alpha Levels at the Indicated Time Points	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
Secondary	Adverse Effects at the Indicated Time Points		Weeks 4, 12, 24