City of Hope, a leading U.S. cancer and diabetes research organization, has launched a phase 1/2 clinical trial investigating whether denosumab, a medication widely used for osteoporosis and bone tumors, could offer a novel treatment approach for early-stage type 1 diabetes.
The multicenter trial aims to determine if denosumab, a human monoclonal antibody already FDA-approved for bone conditions, can protect and potentially regenerate insulin-producing beta cells in patients recently diagnosed with type 1 diabetes.
"This is an exciting new application of a known medication that, in addition to potentially protecting and/or expanding the beta cells that remain in early type 1 diabetes patients, might also be able to help other patients with diabetes to increase beta cell number and/or function," said Dr. Fouad R. Kandeel, the Arthur D. Riggs Distinguished Chair in Diabetes & Metabolism Research at City of Hope and the trial's co-principal investigator.
The Science Behind the Approach
Type 1 diabetes develops when the immune system attacks and destroys beta cells in the pancreas, eliminating the body's ability to produce sufficient insulin to regulate blood glucose. However, in early stages of the disease, some functioning beta cells remain—presenting a potential window for intervention.
Denosumab works in bone treatment by inhibiting a protein called RANKL (Receptor Activator of Nuclear Factor Kappa-B Ligand), preventing its interaction with the RANK receptor and thereby reducing bone damage. City of Hope researchers have discovered that this same pathway affects beta cells in diabetes.
"We have found that the same RANKL/RANK pathway can destroy beta cells," explained Dr. Rupangi Vasavada, associate professor in City of Hope's Department of Translational Research & Cellular Therapeutics and co-principal investigator. "Previous studies in our lab by Nagesha Guthalu Kondegowda, Ph.D. have shown that denosumab can inhibit this detrimental pathway and improve beta cell health by protecting, increasing the number and/or improving the function of beta cells."
By preserving remaining beta cell function, researchers believe denosumab could potentially slow disease progression and improve glycemic control in patients with type 1 diabetes.
Trial Design and Patient Recruitment
The randomized, double-blind trial is currently recruiting participants at three locations: City of Hope in Los Angeles, University of Alabama at Birmingham (led by Dr. Anath Shalev), and Indiana University (led by Dr. Carmella Evans-Molina).
Eligible participants must be adults between 18 and 50 years old who were diagnosed with type 1 diabetes within the past five years and still retain some beta cell function. The study will enroll 45 participants total, with 30 receiving denosumab and 15 receiving placebo in a 2:1 ratio.
The treatment protocol consists of 60mg denosumab injections administered subcutaneously every three months for a total of four injections, with the placebo group receiving saline injections on the same schedule. Participants will be monitored for 12 months to assess safety, changes in beta cell function, and glycemic control parameters.
Funding and Institutional Support
The clinical trial receives primary funding from Breakthrough T1D (formerly JDRF), the leading global type 1 diabetes research and advocacy organization. Additional support comes from The Wanek Family Project for Type 1 Diabetes at City of Hope, an initiative dedicated to finding cures for the disease.
City of Hope brings significant institutional expertise to the trial. Founded in 1913, the organization has grown into one of the largest cancer research and treatment centers in the United States, with a distinguished history in diabetes research. Its contributions include breakthrough cancer medicines, human synthetic insulin, and monoclonal antibodies.
Implications for Diabetes Treatment
If successful, this repurposing of an established medication could represent a significant advancement in type 1 diabetes treatment. Current management primarily focuses on insulin replacement rather than addressing the underlying beta cell destruction.
A therapy that preserves or regenerates beta cells could fundamentally alter the disease trajectory, potentially reducing insulin dependence and improving long-term outcomes for patients. The approach might also have implications for other forms of diabetes where beta cell function is compromised.
The trial's results will be closely watched by the diabetes research community, as positive findings could lead to larger studies and potentially a new treatment option for the estimated 1.6 million Americans living with type 1 diabetes.
