Using denosumab to improve beta cell function in 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

This study is testing if a medication called denosumab can help improve insulin production and blood sugar control in people with early type 1 diabetes.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: City of Hope Medical Center (other)
• Drugs / interventions: Denosumab
• Locations: 3 sites (Birmingham, Alabama and 2 other locations)
• Trial ID: NCT06524960 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of denosumab, a medication typically used for osteoporosis, in improving beta cell function and glycemic control in individuals with early type 1 diabetes (T1D). The study is a Phase 1/2, randomized, double-blind, placebo-controlled trial involving multiple centers. Participants will receive either denosumab or a placebo over a 12-month period, with assessments of beta cell function and blood sugar control through C-peptide levels and HbA1c measurements. The goal is to determine if denosumab can protect beta cells from immune-mediated injury and enhance insulin production.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-50 with early-stage type 1 diabetes and detectable C-peptide levels.

Not a fit: Patients with advanced type 1 diabetes or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could slow the progression of type 1 diabetes and improve blood sugar control for patients.

How similar studies have performed: While the use of denosumab for type 1 diabetes is a novel approach, previous studies have shown promise in protecting beta cells through various mechanisms.

Eligibility criteria

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

  * 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

Main Exclusion Criteria

* 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

Where this trial is running

Birmingham, Alabama and 2 other locations

• University of Alabama at Birmingham — Birmingham, Alabama, United States (RECRUITING)
• City of Hope Medical Center — Duarte, California, United States (RECRUITING)
• Indiana University — Indianapolis, Indiana, United States (RECRUITING)

Study contacts

• Principal investigator: Fouad Kandeel, MD, PhD — City of Hope Medical Center
• Study coordinator: Arthur Riggs Diabetes & Metabolism Research Institute at City of Hope

Conditions: Type 1 Diabetes, Type 1 diabetes, denosumab, HbA1c, beta cell function