Supported Research

Supervisor(s):  Rulan Parekh, Anna Heath

Lay Abstract

Background: Nephrotic syndrome is a common childhood kidney disease which affects 3,000 Canadian children each year. In nephrotic syndrome, the kidneys leak protein into the urine, which causes the body to swell. This causes breathing problems, infections, and blood clots. Most children respond to steroid immune suppression but have multiple disease relapses. These children usually receive other immune-suppressing drugs, which have many side effects. There is an urgent need to find new medications and to improve current treatments for children with nephrotic syndrome. Clinical trials are the best possible way to compare new and current treatments. However, there are many barriers to conducting clinical trials in children with kidney disease. As a result, few clinical trials in children are ever performed or published. This limits a child’s access to safe and effective treatments and exposes them to potential harms.
 
Purpose: Our aim is to test whether low-dose steroids, which could reduce side effects, are as effective as high-dose steroids for treating nephrotic syndrome relapses. We also aim to test which non-steroid medication is most effective for preventing disease relapses.
 
Method: To achieve these aims, we will use new research methods to compare different medications used for nephrotic syndrome. First, we will mimic (“emulate”) a clinical trial comparing the effects of the two most common medications used to prevent relapses (cyclophosphamide and tacrolimus). This will be done using data from an existing study of more than 750 children diagnosed with nephrotic syndrome. We will then simulate the outcomes of different designs of an adaptive clinical trial to compare low-dose vs. high-dose steroids to treat relapses. An adaptive clinical trial allows for planned modifications to a trial after it is started, to make it more efficient and likely to succeed. We will use these simulations to identify which trial design is most efficient and successful. Finally, we will run a pilot study in a small number of children, to find out if it is feasible and safe to perform a full-scale trial comparing low-dose vs. high-dose steroids to treat nephrotic syndrome relapses.
 
Anticipated Outcomes: We expect that we will find important differences in the effectiveness of different medications used to prevent and treat childhood nephrotic syndrome relapses. We expect that an adaptive clinical trial design will perform better than a traditional one (without adaptations) and that a full-scale clinical trial comparing low-dose vs. high-dose steroids to treat nephrotic syndrome relapses will be feasible and safe.
 
Patient Engagement: Patients and parents of children with nephrotic syndrome will be involved in all stages of the design and conduct of this research. We want to better understand patient-oriented research priorities, key clinical trial outcomes, and important differences in these outcome measures to patients. As part of this project, we will build a network of patient partners for future childhood nephrotic syndrome research. Relevance to Patients: Answering these questions would improve the care of children with nephrotic syndrome. These studies will help find the best strategies to prevent and treat disease relapses. This will help let children receive the most effective and least harmful treatment early in their disease. It will also help develop new research methods to compare treatments for other childhood kidney diseases.
 
Conclusion: In summary, we will use new clinical trial research methods to answer key questions that will improve the prevention and treatment of relapses in childhood nephrotic syndrome.