Denosumab for Type 1 Diabetes
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
45 participants
Sep 3, 2024
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria14
- 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
- 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
- GAD specific autoantibodies (GADA);
- Islet-antigen 2 specific autoantibody (IA-2A); and/or
- Zinc Transporter 8 specific autoantibody (ZNT8A)
- Time from T1D diagnosis to screening MMTT must be ≥ 12 months but ≤ 5 years
- Non-fasting C-peptide concentrations of at least 0.2 nmol/L (0.6 ng/ml) at pre-screening and confirmed during a MMTT done at screening visit.
- Serum calcium (corrected for albumin)\* within normal limits per site's local lab
- Agreement by women of childbearing potential (WOCBP) and males of childbearing potential to use a highly effective method of birth control for the course of the study through at least 5 months from the last dose of protocol therapy
Exclusion Criteria13
- History of delayed puberty unless there is radiologic evidence of skeletal maturity
- Use of other investigational agents within 3 months of enrollment
- Vitamin D3 deficiency (\< 30 ng/ml)
- History of anorexia and/or eating disorder
- BMI \> 32 kg/m2
- HbA1c \> 9.5%
- Severe hypoglycemia or diabetic ketoacidosis (DKA) within 3 months prior to screening. Subjects who had such episodes within 3-6 months prior to screening, must have written clearance from their treating physician.
- Use of any of the diabetes medications other than insulin within 3 months of enrollment (e.g., metformin, sulfonylurea, GLP-1 agonists, DPP4 inhibitors, Symlin, SGLT2-inhibitors, amylin)
- Treatment with any of the following drugs in past year: immunosuppressants, anticonvulsant therapy, adrenal or anabolic steroids, calcitonin, selective estrogen receptor modulator, sodium fluoride (other than dental treatment), teriparatide, abaloparatide, strontium or aromatase inhibitors; any history of bisphosphonate treatment.
- Bone fractures (excluding skull, facial bones, metacarpals, fingers, toes and spontaneous fractures associated with severe trauma) within the past 12 months
- Disorders associated with altered skeletal structure or function (Paget's disease, chronic liver disease (liver enzymes \> twice the upper limit of normal), malignancy, hypoparathyroidism or hyperparathyroidism, acromegaly, Cushing's syndrome, hypopituitarism, chronic obstructive pulmonary disease, alcohol intake \> 3 units/day)
- Significant dental/oral disease, including prior history or current evidence of osteonecrosis/osteomyelitis of the jaw, active dental or jaw condition requiring oral surgery, non-healed dental/oral surgery, or planned invasive dental procedures for the course of the study
- Pregnancy or actively breastfeeding (within 6 months prior to screening), or planning to become pregnant with 5 months after last dose of protocol therapy
Interventions
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.
Placebo is 1 mL of normal saline drawn up in a commercially available syringe.
Locations(3)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06524960