Denosumab for Type 1 Diabetes

Recruiting at 4 trial locations

Overseen By Arthur Riggs Diabetes & Metabolism Research Institute at City of Hope

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: City of Hope Medical Center

Must not be taking: Immunosuppressants, Anticonvulsants, Steroids, others

Disqualifiers: Vitamin D3 deficiency, Eating disorder, Obesity, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 months

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether denosumab can aid individuals with early-stage type 1 diabetes by protecting insulin-producing beta cells in the pancreas. Denosumab, already used for bone conditions, may also enhance beta cell function, potentially slowing diabetes progression. The trial compares denosumab to a placebo (a substance with no active ingredient) to assess its impact on blood sugar control. Suitable participants have had type 1 diabetes for at least one year but no more than five years and are not using any diabetes medications other than insulin. As a Phase 1, Phase 2 trial, this research aims to understand how denosumab works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you stop taking any diabetes medications other than insulin within 3 months of enrollment. If you are on other specific medications like immunosuppressants or certain bone-related drugs, you may also need to stop those.

Is there any evidence suggesting that denosumab is likely to be safe for humans?

Research has shown that denosumab is generally safe for people. It is already approved for treating conditions like osteoporosis and certain bone problems related to cancer, indicating its well-established safety for these uses. For instance, individuals with osteoporosis who take denosumab have a lower risk of developing diabetes compared to those who do not, which supports its safety profile.

This trial is in the early stages and aims to ensure that denosumab is safe for people with Type 1 Diabetes (T1D). In lab studies, denosumab showed promise in protecting the insulin-producing cells in the pancreas from damage. This trial will determine if these benefits can be safely achieved in people with T1D. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Denosumab is unique because, unlike standard treatments for Type 1 diabetes that primarily focus on insulin management, this drug targets the immune system. It works by inhibiting a protein called RANKL, which is involved in bone loss and has a role in immune system regulation. Researchers are excited about denosumab because it offers a novel approach by potentially modulating the immune response in Type 1 diabetes, which could lead to better disease management and possibly slow the progression of the condition. This new mechanism of action sets it apart from traditional insulin therapies and other existing diabetes treatments.

What evidence suggests that denosumab might be an effective treatment for type 1 diabetes?

In this trial, participants will receive either denosumab or a placebo. Research has shown that denosumab, a drug originally used for bone issues, might also help with type 1 diabetes (T1D). Studies have found that people taking denosumab have a lower risk of developing diabetes compared to those on other treatments. Lab research suggests that denosumab protects the pancreatic beta cells, which produce insulin, from harm. By safeguarding these cells, denosumab may enhance their function and slow disease progression. Early results from studies on human beta cells are also encouraging, indicating that denosumab could improve their health and performance. ^{1 2 3 4 5}

Who Is on the Research Team?

Fouad Kandeel, MD, PhD

Principal Investigator

City of Hope Medical Center

Rupangi Vasavada, PhD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with early-stage Type 1 Diabetes, where some insulin-producing beta cells are still functioning. The study aims to protect these cells and slow disease progression.

Inclusion Criteria

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

My C-peptide levels are above 0.6 ng/ml, confirmed by a test.

Exclusion Criteria

I have only used insulin for my diabetes in the last 3 months.

I haven't had any bone fractures in the last year.

History of delayed puberty unless there is radiologic evidence of skeletal maturity

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive denosumab 60 mg or placebo subcutaneously every 3 months for a total of 4 injections

12 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Denosumab

Trial Overview The trial is testing Denosumab, a drug normally used for bone-related conditions, to see if it can safeguard the remaining beta cells in Type 1 Diabetes patients and improve their blood sugar control.

How Is the Trial Designed?

Group I: Denosumab Experimental Treatment 1 Intervention

Denosumab 60 mg subcutaneous injection

Group II: Placebo Placebo Group 1 Intervention

Normal Saline 1.0 ml subcutaneous injection

Denosumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Prolia for:

• Osteoporosis in postmenopausal women
• Bone loss associated with hormone ablation therapy for prostate cancer
• Bone loss associated with hormone ablation therapy for breast cancer

Approved in United States as Prolia for:

• Treatment of postmenopausal women with osteoporosis at high risk for fracture
• Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

Approved in Canada as Prolia for:

• Treatment of osteoporosis in postmenopausal women at high risk for fracture
• Treatment to increase bone mass in men with osteoporosis at high risk for fracture

Approved in Japan as Prolia for:

• Treatment of osteoporosis in postmenopausal women
• Treatment of bone loss associated with hormone ablation therapy for prostate cancer

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

Published Research Related to This Trial

Type 1 diabetes remains a serious, life-threatening condition, but there are promising therapies that may help preserve insulin production and improve patient outcomes, particularly through combination treatments.

Immunosuppressive therapies, such as anti-CD3 and anti-CD20 monoclonal antibodies, combined with agents that protect and regenerate β-cells, like GLP-1, could potentially lead to milder disease and even a cure for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapies to Preserve β-Cell Function in Type 1 Diabetes. Ludvigsson, J.[2023]

Denosumab is effective for treating RANKL-mediated disorders in children and adolescents, but it is not always curative and may need to be combined with other treatments or surgery.

Due to potential safety concerns and limited high-level evidence, careful planning and expert oversight are essential to manage risks and define treatment goals when using denosumab in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of RANKL-mediated disorders with denosumab in children and adolescents: a global expert guidance document. Vanderniet, JA., Szymczuk, V., Högler, W., et al.[2023]

Denosumab, a medication used to prevent osteoporosis in patients with low bone mineral density, has been associated with rare cases of hepatotoxicity, including a newly reported case of immune-mediated liver injury in a 43-year-old woman after three years of treatment.

The patient's liver function tests showed significantly elevated levels of liver enzymes, indicating potential drug-induced liver injury, which was confirmed by a liver biopsy revealing chronic inflammation and interface hepatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Denosumab-Induced Immune Hepatitis. Ostrovsky, V., Malnick, S., Ish-Shalom, S., et al.[2021]

In a phase 2 trial involving 84 children and young adults with newly diagnosed type 1 diabetes, golimumab significantly improved endogenous insulin production compared to placebo, as shown by a higher 4-hour C-peptide AUC at week 52 (0.64 vs. 0.43 pmol/mL, P<0.001).

Golimumab also led to a lower requirement for exogenous insulin, with 43% of participants achieving partial remission compared to only 7% in the placebo group, indicating its potential efficacy in preserving beta-cell function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Golimumab and Beta-Cell Function in Youth with New-Onset Type 1 Diabetes. Quattrin, T., Haller, MJ., Steck, AK., et al.[2022]

In a study involving 52 patients with new-onset type 1 diabetes, two courses of teplizumab significantly reduced the decline in insulin production (C-peptide levels) over 2 years, showing a 75% improvement compared to the control group.

Common side effects of teplizumab included rash and upper respiratory infections, but the treatment was effective in preserving insulin production and reducing the need for external insulin in some patients, with specific metabolic and immunologic characteristics helping to identify those who would respond best.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders. Herold, KC., Gitelman, SE., Ehlers, MR., et al.[2021]

Inhibition of the RANKL/RANK pathway using osteoprotegerin and denosumab has been shown to protect both rodent and human β cells from cytokine-induced death, suggesting a potential mechanism for preserving insulin-producing cells in type 1 diabetes.

In vivo studies demonstrated that osteoprotegerin can reverse recent-onset type 1 diabetes in mice, leading to improved glucose control and increased β cell proliferation, indicating its therapeutic potential for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RANKL/RANK is required for cytokine-induced beta cell death; osteoprotegerin, a RANKL inhibitor, reverses rodent type 1 diabetes. Kondegowda, NG., Filipowska, J., Do, JS., et al.[2023]

A 72-year-old woman developed severe liver damage (submassive hepatic necrosis) after receiving denosumab, indicating a potential adverse drug reaction linked to immune response and cytokine induction.

The case highlights that RANKL inhibition by denosumab can lead to significant liver injury, as evidenced by elevated liver enzymes and proinflammatory cytokines, suggesting careful monitoring is needed for patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe hepatocytotoxicity linked to denosumab. Malnick, S., Maor, Y., Melzer, E., et al.[2018]

Denosumab, a monoclonal antibody that inhibits RANKL, shows consistent pharmacokinetics across a large population of 1,076 subjects, including both healthy individuals and cancer patients, indicating its effectiveness in preventing osteoclast activation and survival.

The study found that after administering denosumab, over 95% of patients achieved more than 97% RANKL occupancy, suggesting that dosage adjustments based on body weight, age, race, or tumor type are unnecessary for patients with bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic analysis of denosumab in patients with bone metastases from solid tumours. Gibiansky, L., Sutjandra, L., Doshi, S., et al.[2021]

In a 2-year study involving 1239 patients with rheumatoid arthritis, denosumab 60 mg showed a low incidence of adverse drug reactions (ADRs) at 3.0%, with hypocalcemia and osteonecrosis of the jaw being the most common issues.

Denosumab was effective in preventing the progression of bone erosion in 91.3% of patients, indicating its potential as a safe treatment option for managing rheumatoid arthritis without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of denosumab in Japanese patients with rheumatoid arthritis: a 2-year post-marketing surveillance study. Tanaka, Y., Mizutani, H., Fujii, K., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06524960

NCT06524960 | Denosumab for Type 1 Diabetes 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- ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2814873

Denosumab and the Risk of Diabetes in Patients Treated ... Compared with the comparison group, denosumab treatment was associated with a lower risk of incident diabetes (HR, 0.84; 95% CI, 0.78-0.90).

3. breakthrought1d.org breakthrought1d.org/grants/united-states/california/clinical-trial-of-denosumab-for-type-1-diabetes/

Clinical Trial of Denosumab for Type 1 Diabetes We found that Denosumab improved the health of human beta cells in culture and protected them against diabetes-related injuries, including the cytotoxicity from ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10858399/

Denosumab and the Risk of Diabetes in Patients Treated for ... Compared with the comparison group, denosumab treatment was associated with a lower risk of incident diabetes (HR, 0.84; 95% CI, 0.78-0.90).

5. thejdca.org thejdca.org/publications/report-library/archived-reports/2025-reports/denosumab-a-potential-practical-cure-for-t1d.html

Denosumab: A Potential Practical Cure for T1D? Denosumab for Type 1 Diabetes is a phase I/II trial testing whether injections of Denosumab will protect, expand, and improve beta cell function.