Denosumab for Type 1 Diabetes

July 24, 2025 updated by: City of Hope Medical Center

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
45

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Arthur Riggs Diabetes & Metabolism Research Institute at City of Hope
  • Phone Number: 1-866-44-ISLET(1-866-444-7538)
  • Email: Islets@coh.org

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama at Birmingham
        • Principal Investigator:
          • Anath Shalev, MD
        • Contact:
        • Contact:
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope Medical Center
        • Principal Investigator:
          • Fouad Kandeel, MD, PhD
        • Contact:
          • Fouad Kandeel, MD, PhD
          • Phone Number: 866-444-7538
          • Email: islets@coh.org
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University
        • Contact:
        • Principal Investigator:
          • Carmella Evans-Molina, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Denosumab
Denosumab 60 mg subcutaneous injection
Drug: Denosumab
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 Comparator: Placebo
Normal Saline 1.0 ml subcutaneous injection
Other: Placebo
Placebo is 1 mL of normal saline drawn up in a commercially available syringe.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Primary safety endpoint
Time Frame: 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.
up to 12 months
Primary efficacy endpoint
Time Frame: 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 test
up to 12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Beta cell function
Time Frame: 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
Up to 6 months
HbA1c improvement
Time Frame: 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)].
up to 12 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Glucose variability
Time Frame: up to 12 months

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
Time Frame: up to 12 months

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
City of Hope Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Rupangi Vasavada, PhD, City of Hope Medical Center
  • Principal Investigator: Fouad Kandeel, MD, PhD, City of Hope Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 3, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 11, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 11, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 24, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 24, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 29, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 28, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 24, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 23797
  • JDRF Award:3-SRA-2023-1421-M-B (Other Identifier: JDRF)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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