Denosumab for Type 1 Diabetes
NCT Number: NCT06524960
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Type 1 Diabetes
Interventions: DRUG: Denosumab|OTHER: Placebo
Sponsor: City of Hope Medical Center
Sex: ALL
Age: ADULT
Enrollment: 45
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-10-08
Completion Date: 2026-04-11
Locations: University of Alabama-Birmingham Comprehensive Cancer Center, Birmingham, Alabama, 35233, United States|City of Hope Medical Center, Duarte, California, 91010, United States|Indiana Univ Med Ctr, Indianapolis, Indiana, 46202, United States

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.

Primary Outcome Measures: Primary safety endpoint, 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., up to 12 months|Primary efficacy endpoint, 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 test, up to 12 months
Secondary Outcome Measures: Beta cell function, 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, Up to 6 months|HbA1c improvement, 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 (%) + \[4 x insulin dose (units/kg/24hr)\]., up to 12 months
Other Outcome Measures: Glucose variability, To evaluate the efficacy of denosumab on glucose variability as defined by time in target, and hypoglycemic and hyperglycemic ranges at 6 and 12 months. Glucose variability as defined by percent time in glycemic range (70-180 mg/dl and 70-140 mg/dl) and time spent in hypoglycemic and hyperglycemic ranges from continuous glucose monitoring data in denosumab group will be compared to placebo group.

Glucose variability (baseline and at 6 and 12 months)

- Continuous glucose monitoring, up to 12 months|Insulin sensitivity, To evaluate the efficacy of denosumab on insulin sensitivity as calculated by the HOMA2 formula at 12 months. Insulin sensitivity as measured by HOMA2 in denosumab group will be compared to placebo group.

Insulin sensitivity (baseline and at 12 months), up to 12 months