DOUBLE PRO-TECT Alport: A confirmatory, multicenter, randomized, double-blind, placebo-controlled clinical trial to assess the effect of Dapagliflozin on the progression of chronic kidney disease in adolescents and young adult patients with Alport syndrome

• Applicant: Professor Dr. Oliver Gross
• Subject Area: Nephrology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 508779211

The genetic kidney disease Alport Syndrome, if untreated, leads to end-stage kidney failure early in life - an enormous burden for the patient and their entire family. Alport syndrome leads to increased vulnerability of the kidney filter. The organs get destroyed. In a BMBF-funded study, EARLY PRO-TECT Alport, we were able to demonstrate the benefits and safety of early treatment with antihypertensive drugs (the ACE inhibitor ramipril) in children. This is précised in a videoportrait by the German Ministry with English subtitles (https://www.gesundheitsforschung-bmbf.de/de/videoportrait-hilfe-fur-nierenkranke-kinder-14890.php). The world's first study in children with Alport Syndrome was a great success worldwide: Thanks to the study, the international therapy guidelines for children from 2 years of age were re-written in 2020. ACE inhibitors can slow the disease down, but not cure it: it still progresses. Therefore, in the DOUBLE PRO-TECT Alport study in children and young adults, we now want to investigate whether the disease can be further slowed down by so-called SGLT2 inhibitors. The SGLT2 inhibitor dapagliflozin used here was approved a few months ago for adults with chronic kidney disease. However, in these large studies, which led to approval, dapagliflozin has only been tested on fewer than 8 patients with Alport syndrome. We know from previous studies that ACE inhibitors and SGLT2 inhibitors complement each other by lowering the pressure in the kidney filter. In our study, we want to prove that in adolescents with Alport Syndrome, the particularly vulnerable kidney filters can be protected. In Germany, over 1000 young people with Alport syndrome have chronic kidney disease and are hoping for better therapies so that they do not need dialysis too early. However, Alport Syndrome is too rare (and therefore too uninteresting commercially) for pharmaceutical companies to be investigated for special therapies. This is why families and doctors need the DOUBLE PRO-TECT Alport study. Only this study can show how great the potential of SGLT2 inhibitors is to delay kidney disease in many of our patients, perhaps even until retirement age.

• DFG Programme: Clinical Trials