Immunoglobulin A Nephropathy [IgAN], is a chronic disease affecting the kidneys. It is caused by the production of abnormal antibodies, also called immunoglobulins (Ig), in particular abnormal IgA (type of immunoglobulin). An antibody (Ab) is a large, Y-shaped protein that is used by the immune system to neutralize pathogens, such as pathogenic bacteria and viruses. With IgAN, the production by the body of abnormal antibodies of the IgA family trigger the formation of other antibodies because the body sees the abnormal antibodies as foreign and wants to clear them. As a result, the abnormal antibodies of the IgA family together with the subsequent antibodies the body creates, form circulating immune complexes. These can deposit in the kidneys and trigger an inflammatory response, causing damage.
There is no proven effective immunosuppressive treatment for IgA nephropathy in South Asian patients although it is known to have worse kidney outcomes when compared to Western population. We are proposing a multi-center clinical trial with multiple treatment arms and multiple stages to assess whether the already available and approved generic drugs can be repurposed in addition to the usual treatment as against usual treatment alone for effectively decreasing urine protein and improving outcomes in adult Indian patients with IgAN at high risk of progression. The patient reported outcome measures will be assessed to inform important concerns of the participants before and after treatment. The adverse profile and treatment adherence will be enumerated. Other candidate biomarkers and their change with treatment will also be studied.
In the study that you are considering today, 585 participants will be enrolled from up to 11 sites in India.
This study has been reviewed and approved by the Institutional Review Board [IRB], Christian Medical College and other sites that the study can take place. They are responsible for making sure that the rights of people who take part in clinical research studies are protected.
There is no novel treatment planned in this clinical trial. In this study, the drugs used in this clinical trial are already approved by the Drugs Controller General of India (DCGI) who is the head of department of the Central Drugs Standard Control Organization (CDSCO) of the Government of India for treatment in a broad range of CKD conditions in different populations and are being repurposed for South Asian IgAN treatment.
The screening visit will take place at the trial site clinic up to 7 days prior to the first day of the clinical trial. Blood and urine tests will be done to assess for eligibility. Eligible participants will attend the Day 1 visit at the trial site clinic. After starting the medication, you will be asked to report in person at the study site every 3 months, which is part of standard clinical care. Relevant medical history, symptom driven physical examination, concomitant medication review, vitals, height, weight, blood, and urine tests will be done. You will be remotely monitored by clinical trial coordinators once every 2 weeks for blood pressure readings, emphasized on salt restriction, proper sugar control if diabetic, maintenance of patient diaries, assessment of medication adherence, monitoring of side effects. Participants will complete the follow-up visit in Week 104 at which time final assessments will be performed. Since this is a pragmatic real-world trial, remote monitoring is also built in if you are unable to visit the study site for a maximum of 6 months.
What are the benefits if you take part in this Study?
There is no proven effective treatment for Immunoglobulin A nephropathy. Also, the outcomes of IgA nephropathy are poor in South Asian patients as shown in our previous study when compared to the Western population. Hence, the outcomes of this randomized controlled study may provide evidence for our population
Will you have to pay for the study drug?
Interventions and background therapy will be given free in the trial. Since it is a pragmatic trial involving commonly available and approved drugs and follow up visits are as per regular clinical visits, there is no additional payments. Also, each participant will receive a digital BP apparatus for home monitoring of BP.
What is the compensation mechanism for study- related injuries?
The study is covered by insurance for any compensations for research related injury.
These interventions are already in use for various glomerulonephritis, and the main aim of the study is to generate evidence of efficacy for its continued use. The potential adverse events are summarized below, and the most common are gut disturbances.
Drug name |
Potential adverse events |
Hydroxychloroquine |
Atrioventricular block, sick sinus syndrome, retinopathy 4%, hemolysis <1%, |
Mycophenolate mofetil |
Leucopenia, anaemia, diarrhea, abdominal pain 14%, nausea, diarrhea 24%, vomiting 20%, increased risk of infection, edema 17%, abnormal hepatic function tests <10% |
Oral Steroids and gut directed budesonide |
Fluid retention, impaired glucose tolerance, menstrual disease, increased appetite, pancreatitis, infection, Cushing syndrome |
Sodium-glucose cotransporter-2 inhibitors |
Acute kidney injury, volume depletion, ketoacidosis, dyslipidemia 3%, nausea 3%, genitourinary fungal infection (3 to 8%) |
Angiotensin receptor blockers |
Acute kidney injury (reversible), hyperkalemia, hypotension 4%, palpitations <2%, anemia 4%, cough 3% |
During the study, your personal data (e.g., birthdate, gender, race, health information) will be collected, stored in REDCap database with a unique ID. This ID will be used on all study documents to protect your identity. Data will be securely stored in a protected database with restricted access, and your full identity will never appear on study records or samples.
Only the study doctor can link your ID to your personal information, which will be kept confidential. Study results may be published, but you will never be identified by name. Your data will be stored securely for at least five years after the trial.
Taking part in this trial is entirely your decision. Deciding to participate will not affect any other medical treatments you are receiving from your doctors.
If you choose to attend the first study appointment, you will have the chance to ask any questions about the study. After reviewing your blood and urine tests, the hospital doctor leading the trial at your hospital or your GP will confirm if it’s appropriate for you to join. We will also inform your hospital or GP that you wish to participate.
By joining this study, you will help advance efforts to improve care for people with kidney problems and potentially reduce the need for dialysis in the future.
Your participation is completely your choice. If you choose not to participate, or to leave the study at any time point (by informing your Study Doctor), it will not affect your usual medical care. If you agree to participate, please give your consent in writing. If you withdraw your consent, no new information will be taken and you may request that no new analysis on your coded samples be done. If you withdraw from the study, your vital status may be obtained at study end through review of your medical records, according to local guidelines and as allowed by local regulations, unless you object and notify your study doctor.
Sample Storage and Biomarker Analysis
With written informed consent, blood and urine samples will be collected and stored in appropriate containers. DNA will be extracted from the blood samples. All specimens will be preserved at -20°C for up to one month, or at -80°C for long-term storage.
Exploratory Biomarkers
Serum and plasma samples will be collected to assess exploratory biomarkers that may help improve our understanding of disease mechanisms and treatment responses. These may include BLyS, APRIL, Gd-IgA1-containing immune complexes, anti-Gd-IgA1 autoantibodies, C3, and C4. Additional biomarkers may be added during or after the study if scientifically relevant, while any of the listed markers may be excluded if they are no longer considered useful.
Sample collection will follow the time points outlined in the Schedule of Assessments. After the study concludes, exploratory biomarker samples may be stored at a central biobank at Christian Medical College (CMC), Vellore, for up to 15 years to support future analyses. Samples will be shipped in batches to this central storage facility.
