$5.6M grant will test weight-loss drugs in kidney disease

A groundbreaking Australian study will be extended to investigate the potential for semaglutide – one of the class of medicines used to treat type 2 diabetes and obesity - to slow the progression of chronic kidney disease (CKD), thanks to a $5.6 million grant from the NHMRC’s Clinical Trials & Cohort Studies program.

Led by Associate Professor Sradha Kotwal, Program Head of Renal and Metabolic at The George Institute for Global Health, and Conjoint A/Prof at UNSW Sydney, the international Phase III CAPTIVATE trial is a flexible, multi-domain clinical trial platform that allows rapid study of benefits and side effects in different treatment combinations in people living with CKD. Five countries (India, Sri Lanka, Spain, New Zealand and Australia) are involved in the study to date.

The new grant adds semaglutide (a GLP-1 receptor agonist) as a treatment option to the existing arms of CAPTIVATE, which are testing other new classes of medications, including a mineralocorticoid receptor antagonist (MRA) and an endothelin receptor antagonist alone and in combination, to try and uncover what role these novel therapies might play in addressing the high unmet need for effective CKD treatments.

Initially developed for blood sugar control in diabetes, GLP-1s have also been approved and widely adopted for weight loss. They have since shown broad therapeutic potential in a growing range of other conditions, possibly due to their anti-inflammatory effects.

CAPTIVATE is the first trial to test the use of a GLP-1 in general CKD by using a platform trial design, on its own for non-diabetic CKD and in combination with other agents.

The addition of GLP-1s will allow researchers to explore their unique therapeutic value and accelerate the discovery of more effective, combination-based treatment strategies.

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We are excited to be able to incorporate a GLP-1 into our CAPTIVATE trial. This class is already transforming care in diabetes and weight management, and emerging evidence suggests they may offer powerful benefits for kidney health as well. This funding gives us a unique opportunity to explore their potential and find new strategies for slowing the progression of chronic kidney disease and improving outcomes for millions of patients globally.

By:

A/Prof Sradha Kotwal, Program Head - Renal and Metabolic, The George Institute for Global Health

Professor Kotwal said that usually clinical research requires single studies for each therapy, with different patients needing to be enrolled each time. After each intervention is tested, infrastructure such as study databases, statistical approaches, and site networks are dismantled.

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The flexible design of the CAPTIVATE platform allows for ongoing recruitment and patient follow-up, adding or removing treatments, adding new countries, and modifying patient selection based on how they’re responding, without needing to set up infrastructure each time there is a new intervention to test. This saves both time and money, meaning benefits shown can be translated more quickly into practice to potentially help millions living with CKD.

By:

A/Prof Kotwal

Chronic kidney disease (CKD) is a progressive disease that can lead to kidney failure, heart disease, disability, and premature death with 10% of people worldwide estimated to have CKD. The number of people living with CKD continues to rise, caused by the increase in diabetes, placing a growing burden on patients, carers and healthcare systems.

References

1. Australian Institute of Health and Welfare. Chronic kidney disease: Australian facts, Mortality [Internet]. Australian Institute of Health and Welfare. 2023. Available from:  https://www.aihw.gov.au/reports/chronic-kidney-disease/chronic-kidney-disease/contents/mortality

2. Australia & New Zealand Dialysis & Transplant Registry. Chapter 3: Mortality & End Stage Kidney Disease. 2019. Available from:  https://www.anzdata.org.au/wp-content/uploads/2019/09/c03_mortality_2018_ar_2019_v1.0_20191202.pdf