Primary IgA NephropathyPhase 4HCQIgANNCT02765594
Hydroxychloroquine Sulfate Alleviates Persistent Proteinuria in IgA Nephropathy
A Phase 4 study testing Hydroxychloroquine Sulfate and Valsartan in people with Primary IgA Nephropathy, run by Peking Union Medical College Hospital at 1 site in China.
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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Primary IgA Nephropathy
- What is being tested?
- Hydroxychloroquine Sulfate and Valsartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 98 participants
- Where
- 1 siteChina
- Study dates
- Jun 2016to Jun 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- biopsy proven primary IgA nephropathy
- age 18-60 years
- proteinuria range from 0.5 to 1.5g/d
- serum creatinine ≤132.6μmol/L
- normal blood pressure or blood pressure ≤130/80 mmHg in patients with hypertension
Who cannot join
- Hypersensitivity to chloroquine or to hydroxychloroquine
- blood pressure <90/60 mm Hg
- pregnancy and breastfeeding women
- renal artery stenosis
- Rapidly progressive renal insufficiency
- systemic lupus erythematosus or other connective tissue diseases
Show all 19Show fewer
- Henoch- schoenlein purpura
- other nephritis
- diabetes mellitus
- retinopathy
- other contraindication of hydroxychloroquine
- severe hepatic insufficiency
- G6PD deficiency
- psoriasis or porphyria
- malignant hypertension
- viral hepatitis or other infections
- treatment with steroids or cytotoxic drugs during the previous three months
- psychiatric disorder
- not suitable for the study judged by investigator
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peing Union Medical College Hospital
Beijing, 100730
Ruitong Gao, MD, 86-010-69155058, gaoruitong@gmail.com
About this study
Official title: 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.
Read the 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
- Being tested
- Hydroxychloroquine Sulfate, Valsartan
- Keywords
- 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
- Medical subject headings
- Glomerulonephritis, IGA, Kidney Diseases, Autoimmune Diseases, Glomerulonephritis, Nephritis, Immune System Diseases, Urologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxychloroquine SulfateDrug
Also called Fenle
200mg bid
ValsartanDrug
Also called Diovan
160mg qd
| Study group | Role | What they receive |
|---|---|---|
| valsartan only:control group | Experimental | valsartan (160mg/d) Receives: Drug: Valsartan |
| hydroxychloroquine with valsartan:study group | Experimental | valsartan (160mg/d) and Hydroxychloroquine Sulfate ( 400mg/d, twice daily) Receives: Drug: Hydroxychloroquine Sulfate; Drug: Valsartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 weeks
Secondary outcomes (8)
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.
Measured: Baseline and Weeks 4, 12, 24
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.
Measured: Baseline and Weeks 4, 12, 24
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.
Measured: Baseline and Weeks 4, 12, 24
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.
Measured: Baseline and Weeks 4, 12, 24
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.
Measured: Baseline and Weeks 4, 12, 24
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.
Measured: Baseline and Weeks 4, 12, 24
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.
Measured: Baseline and Weeks 4, 12, 24
Adverse Effects at the Indicated Time Points
Measured: Weeks 4, 12, 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2016 (estimated)
- Study startJun 2016
- Primary completionMay 2019 (estimated)
- Study completionJun 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary IgA NephropathyStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 98 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- RUITONG GAO, MD, Study director, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02765594
- Sponsor's protocol ID
- PUMCHHCQIgAN01
- Acronym
- HCQIgAN
- Status last verified
- Sep 2017
- First submitted
- 30 Apr 2016
- Last updated
- 20 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 38299639
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydroxychloroquine Sulfate Alleviates Persistent Proteinuria in IgA Nephropathy:a Single Center Prospective Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT02765594
- Acronym / sponsor ID
- HCQIgAN / PUMCHHCQIgAN01
- Conditions
- Primary IgA Nephropathy
- Keywords
- Glomerulonephritis, IGA, Kidney Diseases, Autoimmune Diseases, Glomerulonephritis, Nephritis, Immune System Diseases, Urologic Diseases, Hydroxychloroquine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 98 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- Jun 2016 (actual)
- Primary completion
- May 2019 (estimated)
- Study completion
- Jun 2019 (estimated)
- First posted
- 6 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| valsartan only:control group | Experimental | Drug: Valsartanvalsartan (160mg/d) |
| hydroxychloroquine with valsartan:study group | Experimental | Drug: Hydroxychloroquine Sulfate, Drug: Valsartanvalsartan (160mg/d) and Hydroxychloroquine Sulfate ( 400mg/d, twice daily) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- biopsy proven primary IgA nephropathy
- age 18-60 years
- proteinuria range from 0.5 to 1.5g/d
- serum creatinine ≤132.6μmol/L
- normal blood pressure or blood pressure ≤130/80 mmHg in patients with hypertension
Key exclusion criteria (19 listed)
- Hypersensitivity to chloroquine or to hydroxychloroquine
- blood pressure <90/60 mm Hg
- pregnancy and breastfeeding women
- renal artery stenosis
- Rapidly progressive renal insufficiency
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxychloroquine SulfateAlso: Fenle200mg bid | Drug | hydroxychloroquine with valsartan:study group |
| ValsartanAlso: Diovan160mg qd | Drug | hydroxychloroquine with valsartan:study group, valsartan only:control group |
Primary outcome
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.
8 secondary outcomes
Change from Baseline in Proteinuria Levels at the Indicated Time Points
Time frame: 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
Change from Baseline in eGFR at the Indicated Time Points
Time frame: 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
Change from Baseline in Serum Interleukin-6 Levels at the Indicated Time Points
Time frame: 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
Change from Baseline in Serum Tumor Necrosis Factor alpha Levels at the Indicated Time Points
Time frame: Baseline and Weeks 4, 12, 24
Adverse Effects at the Indicated Time Points
Time frame: Weeks 4, 12, 24
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2017.
- Derived from this study: PubMed 38299639Tunnicliffe 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
RUITONG GAO, MD study director
Peking Union Medical College Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hydroxychloroquine Sulfate and Valsartan in people with Primary IgA Nephropathy, run by Peking Union Medical College Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact RUITONG GAO, MD (86-010-69155058, gaoruitong@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Remission (Complete [CR] or Partial [PR]) at Week 24 (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02765594, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2017.