Denosumab for Type 1 Diabetes
- Registration Number
- NCT06524960
- Lead Sponsor
- City of Hope Medical Center
- Brief Summary
Type 1 diabetes (T1D) arises from abnormal immune cell-mediated injury to beta cells that make insulin. The injured beta cells can then no longer make the needed amount of insulin to stay healthy. However, in the early stages of T1D, some beta cells are still alive and functioning. Treatment to protect the beta cells against injury at this time could slow the progress of disease. Denosumab is an approved treatment for osteoporosis (a disease that thins and weakens the bones), high blood calcium levels, bone cancer, and other bone problems in patients who have cancer. The research team has found that the bone pathway that denosumab works on to treat these bone conditions also has effects on the health of the beta cells. Lab studies suggest that denosumab may protect and/or increase the number of beta cells and improve how well they work. This study will test whether denosumab is safe and improves beta cell function and blood sugar control in people with early T1D.
- Detailed Description
This is a Phase 1/2, prospective, randomized, double-blind, placebo-controlled, multi-center clinical trial to evaluate the safety and efficacy of denosumab for improving beta cell function and glycemic control among patients with early T1D and detectable C-peptide. The efficacy of denosumab will be evaluated by changes in C-peptide level during mixed meal tolerance test and achieving a clinically meaningful HbA1c reduction at 12 months. Subjects will be followed for 12 months for adverse events and for changes in beta cell function and glycemic control parameters.
Subjects will be randomized with a 2:1 treatment to placebo ratio. The treatment group will enroll 30 subjects with the denosumab regimen of 60 mg given subcutaneously every 3 months for a total of 4 injections. The placebo arm will enroll 15 subjects and be administered with normal saline placebo given subcutaneously every 3 months for a total of 4 doses.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 45
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Denosumab Denosumab Denosumab 60 mg subcutaneous injection Placebo Placebo Normal Saline 1.0 ml subcutaneous injection
- Primary Outcome Measures
Name Time Method Primary efficacy endpoint up to 12 months To evaluate the efficacy of denosumab in improving beta cell function in T1D subjects as measured by difference of mean area under the curve (AUC) of plasma C-peptide during 2-hr mixed meal tolerance test (MMTT) at baseline and 12 months after initiation of treatment (primary efficacy endpoint). Beta cell function as determined by the change in C-peptide AUC during MMTT in denosumab group will be compared to placebo group at 12 months from baseline.
Change in Beta cell function (baseline and at 12 months)
- Mixed meal tolerance testPrimary safety endpoint up to 12 months To evaluate the safety of denosumab as assessed by the occurrence of adverse events (primary safety endpoint). Occurrence of treatment-related adverse events in denosumab group compared to placebo group during the 12 months.
Toxicity: Toxicity and adverse events (except hypoglycemia and DKA) will be recorded in the eCRFs using the NCI CTCAE v 5.0 (See Section 7.0 for specific AEs). Hypoglycemia and DKA events will be defined per Section 14.1.1.
- From treatment day through Month 12: All grade toxicities/AEs will be recorded.
Safety will be assessed at baseline and at 3, 6, 9 and 12 months.
- Secondary Outcome Measures
Name Time Method HbA1c improvement up to 12 months To evaluate the efficacy of denosumab in improving HbA1c and insulin-dose adjusted HbA1c (IDAAIC) at 12 months. Changes in HbA1c and IDAAIC in denosumab group compared to placebo group.
Glycemic Control (baseline and at 3, 6, 9 and 12 months)
* HbA1c
* IDAAIC is calculated as HbA1c (%) + \[4 x insulin dose (units/kg/24hr)\].Beta cell function Up to 6 months To evaluate the efficacy of denosumab in improving beta cell function as measured by C-peptide AUC during MMTT at 6 months. Beta cell function as determined by C-peptide AUC during MMTT in denosumab group will be compared to placebo group at 6 months.
Beta cell function (baseline and at 6 months)
- Mixed meal tolerance test
Trial Locations
- Locations (3)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
City of Hope Medical Center
🇺🇸Duarte, California, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States