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Hydroxychloroquine Sulfate Alleviates Persistent Proteinuria in IgA Nephropathy (HCQIgAN)

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ClinicalTrials.gov Identifier: NCT02765594
Recruitment Status : Unknown
Verified September 2017 by Peking Union Medical College Hospital.
Recruitment status was:  Recruiting
First Posted : May 6, 2016
Last Update Posted : September 20, 2017
Sponsor:
Information provided by (Responsible Party):
Peking Union Medical College Hospital

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.

Condition or disease Intervention/treatment Phase
Primary IgA Nephropathy Drug: Hydroxychloroquine Sulfate Drug: Valsartan Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 98 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hydroxychloroquine Sulfate Alleviates Persistent Proteinuria in IgA Nephropathy:a Single Center Prospective Randomized Controlled Study
Actual Study Start Date : June 2016
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : June 2019


Arm Intervention/treatment
Experimental: valsartan only:control group
valsartan (160mg/d)
Drug: Valsartan
160mg qd
Other Name: Diovan

Experimental: hydroxychloroquine with valsartan:study group
valsartan (160mg/d) and Hydroxychloroquine Sulfate ( 400mg/d, twice daily)
Drug: Hydroxychloroquine Sulfate
200mg bid
Other Name: Fenle

Drug: Valsartan
160mg qd
Other Name: Diovan




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Adverse Effects at the Indicated Time Points [ Time Frame: Weeks 4, 12, 24 ]


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02765594


Contacts
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Contact: RUITONG GAO, MD 86-010-69155058 gaoruitong@gmail.com

Locations
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China
Peing Union Medical College Hospital Recruiting
Beijing, China, 100730
Contact: Ruitong Gao, MD    86-010-69155058    gaoruitong@gmail.com   
Sponsors and Collaborators
Peking Union Medical College Hospital
Investigators
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Study Director: RUITONG GAO, MD Peking Union Medical College Hospital

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Responsible Party: Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT02765594    
Other Study ID Numbers: PUMCHHCQIgAN01
First Posted: May 6, 2016    Key Record Dates
Last Update Posted: September 20, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Peking Union Medical College Hospital:
Glomerulonephritis, IGA
Kidney Diseases
Autoimmune Diseases
Glomerulonephritis
Nephritis
Immune System Diseases
Urologic Diseases
Hydroxychloroquine
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Antirheumatic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
interleukin-6
interferon-alpha
tumor necrosis factor-alpha
Additional relevant MeSH terms:
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Kidney Diseases
Proteinuria
Glomerulonephritis, IGA
Urologic Diseases
Urination Disorders
Urological Manifestations
Signs and Symptoms
Glomerulonephritis
Nephritis
Autoimmune Diseases
Immune System Diseases
Hydroxychloroquine
Valsartan
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Antirheumatic Agents