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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT02765594
Other study ID # PUMCHHCQIgAN01
Secondary ID
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
Health authority
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

Study Design


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
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