Impact of Dapagliflozin for the Regulation of Immunological Activity in Membranous
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- To measure immunological activity (anti-PLA2R1 antibody concentration) in anti-PLA2R1 antibodies positive MN patients undergoing an immunological relapse, before and after 6 months of dapagliflozin treatment.
研究概览
简要总结
WHY IS THIS RESEARCH BEING CONDUCTED? Membranous glomerulonephritis (MN) is an autoimmune disease that affects the kidneys through autoantibodies, meaning that antibodies produced by your body attack your own kidney cells. The appearance of these autoantibodies can be explained in part by a disruption in the immune response. Patients with this disease are treated with immunosuppressive drugs such as rituximab. The aim of this treatment is to reduce the production of all antibodies, including those responsible for the disease. Despite this treatment, some patients may experience a relapse of the disease. These relapses can be complicated by infections, blood clots in the blood vessels, and, in the long term, can lead to kidney failure and an increased cardiovascular risk. Relapses can also have an impact on patients' social and professional lives.
Dapagliflozin is a diuretic medication, which means that it is used to increase urine production and eliminate excess salt and water from the body to reduce edema (swelling). It is currently prescribed and authorized for patients with type 2 diabetes, heart failure and chronic kidney disease. This treatment has been shown to reduce the amount of proteins in the urine and protect the kidneys and cardiovascular system in patients with chronic kidney disease. A study has also shown that dapagliflozin may have an effect on the immune response.
WHAT DOES IT INVOLVE? The aim of our study will be to evaluate the efficacy of dapagliflozin in reducing disease autoantibodies and preventing relapses.
This research will be conducted at the Nice University Hospital and the Nîmes University Hospital. We expect to 20 patients to be recruited with an anti-PLA2R1 positive MN.
Participation in the study will last 6 months. The research is funded by Nice University Hospital. WHAT IS THE TREATMENT BEING STUDIED? It is dapagliflozin, a drug that is increasingly used routinely in patients with nephrotic syndrome (including MN) for its ability to reduce protein in the urine. Its effect on the immune system in MN has not yet been studied
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 84 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants ≥ 18 years old and < 85 years old;
- •Membranous Nephropathy associated with anti-PLA2R1 autoantibodies;
- •Urine Protein Creatinine Ratio (UPCR) between 0.5 g/g and 3.5 g/g;
- •Immunological relapse defined by an increase in anti-PLA2R1 antibody concentration > 14 RU/mL after a phase of anti-PLA2R1 antibody negativation, (i.e. immunological remission) and complete or partial clinical remission;
- •Antiproteinuric treatment at maximal and stable dose. According to KDIGO 2024 guidelines on management of glomerular diseases and the French recommendations (PNDS GEM 2022), symptomatic treatment of membranous nephropathy should include: (i) a low sodium diet, (ii) a diuretic and (iii) an angiotensin-converting enzyme inhibitor or an angiotensin 2 receptor blocker at maximal tolerated dose (i.e., absence of orthostatic hypotension and no increase in serum creatinine >30%).
排除标准
- •Immunosuppressive treatment for MN in the 6 months prior to the selection visit;
- •Secondary MN (associated with cancer, infectious disease, autoimmune or iatrogenic disease);
- •Active nephrotic syndrome defined according to KDIGO guidelines as proteinuria > 3.5 g/day (or 3.5 g/g in a urine sample) and albumin < 30 g/L;
- •No previous history of immunological remission (anti-PLA2R1 antibodies < 14 RU/mL in ELISA or negative indirect immunofluorescence) or clinical remission (partial or complete);
- •Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption disorders
- •Patients at risk for ketoacidosis including patients with a low reserve of functional beta cells (e.g. patients with type 2 diabetes with low C-peptide or latent autoimmune diabetes mellitus or patients with a history of pancreatitis or patients who are receiving insulin treatment), patients with conditions leading to reduced food intake or severe dehydration, patients with low insulin reserve, and patients with increased insulin requirements due to acute medical illness, surgery or excessive alcohol consumption;
- •Type 1 diabetes;
- •Pregnancy or breastfeeding;
- •Estimated CKD-EPI Glomerular Filtration Rate (eGFR) < 25 ml/min/1.73m2;
- •Severe liver failure (Child-Pugh stage C);
- •NYHA functional class IV heart failure;
- •Patients already currently receiving dapagliflozin or another SGLT2 inhibitor for another condition;
- •Repeated urinary tract infections;
- •Hypersensitivity to the active substance or excipients.
研究组 & 干预措施
FORXIGA
干预措施: Forxiga (Drug)
结局指标
主要结局
To measure immunological activity (anti-PLA2R1 antibody concentration) in anti-PLA2R1 antibodies positive MN patients undergoing an immunological relapse, before and after 6 months of dapagliflozin treatment.
时间窗: 6 months
Change in anti-PLA2R1 antibody titer (ELISA titer in RU/mL) from baseline to 6 months after dapagliflozin treatment compared with pretreatment antibody titer.
次要结局
- To measure the change in proteinuria over the course of the study in anti-PLA2R1 antibodies positive MN patients undergoing an immunological relapse(6 months)
- To measure the change in serum albumin levels over the course of the study in anti-PLA2R1 antibodies positive MN patients undergoing an immunological relapse(6 months)
- To measure the occurrence of clinical relapses over the course of the study in anti-PLA2R1 antibodies positive MN patients undergoing an immunological relapse(6 months)
- To measure the change in glomerular filtration rate over the course of the study in anti- PLA2R1 antibodies positive MN patients undergoing an immunological relapse(6 months)
- To measure the production of Th17, Th2 and Treg pathway cytokines in anti-PLA2R1 antibodies positive MN patients undergoing an immunological relapse, before and after 6 months of dapagliflozin treatment(6 months)
- To assess the dapagliflozin treatment's safety in MN patients(6 months)