A Phase 1/2 Prospective, Randomized, Double-blind, Placebo-controlled Multi-center Clinical Trial to Determine the Safety and Efficacy of Denosumab in Improving Beta Cell Function and Glycemic Control Among Patients With Type 1 Diabetes
City of Hope Medical Center
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.
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…
Eligibility
- Age range
- 18–50 years
- Sex
- All
- Healthy volunteers
- No
Main Inclusion Criteria * Age: Females 18-50 years; males 21-50 years (minimum age based on skeletal maturity) * Diagnosis of type 1 diabetes (T1D) based on ADA Criteria: * Hyperglycemia (glycosylated hemoglobin (HbA1c) ≥ 6.5%; OR * fasting plasma glucose ≥ 126 mg/dl (7.0 mmol/L); OR * 2-hour plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test; OR * In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥ 200 mg/dl (11.1 mmol/L) * Documented history of at least one type 1 diabetes associated autoantibody * GA…
Interventions
- DrugDenosumab
Denosumab is a sterile, preservative-free, clear, colorless to pale yellow solution. Each 1 mL single-dose prefilled syringe of denosumab contains 60 mg denosumab (60 mg/mL solution), 4.7% sorbitol, 17 mM acetate, 0.01% polysorbate 20, Water for Injection (USP), and sodium hydroxide to a pH of 5.2.
- OtherPlacebo
Placebo is 1 mL of normal saline drawn up in a commercially available syringe.
Locations (3)
- University of Alabama at BirminghamBirmingham, Alabama
- City of Hope Medical CenterDuarte, California
- Indiana UniversityIndianapolis, Indiana