Treatment of acute Charcot foot in diabetes patients with Denosumab

Efficacy of Treatment With DENOsumab of an Acute CHARCOT Foot in Patients With Diabetes. A Multicenter, Double-blind, Randomized, Placebo-controlled Trial.

This study is testing if Denosumab can help people with diabetes who have acute Charcot foot feel better and recover faster compared to those who get a placebo.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 38 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Bispebjerg Hospital (Academic / other)
• Drugs / interventions: Denosumab
• Locations: 8 sites (Aalborg and 7 other locations)
• Trial ID: NCT04547348 on ClinicalTrials.gov

What this trial studies

This trial aims to evaluate the effectiveness of Denosumab in treating acute Charcot foot in patients with diabetes. Participants will be randomly assigned to receive either Denosumab or a placebo, with a follow-up period of 52 weeks to monitor clinical outcomes. The primary goal is to determine the time until full remission of Charcot foot, assessed through clinical evaluations and radiological imaging. The study will also include blood tests and sensory examinations to gather comprehensive data on patient health.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-80 with type 1 or type 2 diabetes diagnosed for more than three months and presenting with acute Charcot foot.

Not a fit: Patients with chronic Charcot foot lasting more than three months or those with existing foot ulcers may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve recovery outcomes for patients suffering from acute Charcot foot due to diabetes.

How similar studies have performed: While this approach is novel in the context of Charcot foot treatment, similar studies using Denosumab for other conditions have shown promising results.

Eligibility criteria

Inclusion Criteria:

* Age 18-80 years
* Type 1 or type 2 diabetes (diagnosed diabetes for more than 3 months)
* Diagnosed with acute Charcot foot defined as a unilateral red, swollen and warm foot, with a difference of skin temperature of more than 2 °C compared with the unaffected foot and with sign of Charcot on either x-rays of the foot, MRI, bone scintigram or PET/CT.
* Peripheral neuropathy: Previously diagnosed and/or biothesiometri: \> 25 V or lack of sensation of 10 grams monofilament on 1. toe at the acute Charcot foot.

Exclusion Criteria:

* Duration of the acute Charcot foot for more than 3 months (at the screening visit).
* Existing foot ulcer on the affected foot
* Previous acute or chronic Charcot of the affected foot
* Planned surgery on the acute Charcot foot
* Infection (cellulitis or osteomyelitis) of the affected foot (clinically and/or radiologically proven)
* Previous midfoot or proximal to mid foot amputation of the affected foot
* Hypocalcemia (Serum Calcium \<2.1 mmol/L or Calcium ion \< 1.12 mmol/L)
* Vitamin D deficiency (Serum 25-hydroxyvitamin D \< 50 nmol/L)
* Renal failure (serum creatinine \>200 mmol/L or eGFR \< 30 ml/min).
* Treatment with Denosumab within the last 12 months. • Have a known hypersensitivity to Denosumab • History of osteonecrosis of the jaw.
* Poor oral hygiene, which is defined as within 3 months of a tooth extraction, dental implants or mandibular surgery
* Planned mandibular surgery or dental implants within the next 12 months.
* Prior non-traumatic vertebral fracture
* Treatment with medication known to affect bones within the last 12 months (such as bisphosphonates, Forsteo®, calcitonin, Protelos®, selective estrogen receptor modulators, glucocorticoids and sex hormones)
* Active or chronic liver disease \*Chronic liver disease is defined as clinical history of decompensated chronic liver disease (ascites, encephalopathy or variceal bleeding) \*Acute Liver disease is defined as an INR of \> 1.5 (in the absence of the use of Warfarin) and AST and ALT \> 2 x ULN
* History of inflammatory arthropathies (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, autoimmune arthropathy)
* Pre-existing medical condition judged to preclude safe participation in the study
* Current treatment with cytotoxic drugs or with systemically administered glucocorticoids
* Abuse of alcohol or drugs, or presence of any condition that in the Investigators opinion may lead to poor adherence to study protocol
* Pregnancy, breast feeding or planning pregnancy or not using adequate contraceptive methods. The following contraceptive products are considered to be safe: Intrauterine devices or hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting injections).
* Likely inability to comply with the visits because of planned activity
* Use of any investigational product with the last month.
* Use of any drug or any other reason which in the Investigator's opinion could interfere with the outcome of the treatment of the acute Charcot foot.
* Cancer, or any clinically significant disease or disorder, except for conditions associated to the diabetes, which in the Investigator's opinion could interfere with the results of the trial

Where this trial is running

Aalborg and 7 other locations

• Steno Diabetes Center North — Aalborg, Denmark (Recruiting)
• Steno Diabetes Center Aarhus — Aarhus, Denmark (Recruiting)
• Bispebjerg Hospital — Copenhagen NV, Denmark (Recruiting)
• Steno Diabetes Center Copenhagen — Gentofte Municipality, Denmark (Recruiting)
• Nordsjællands Hospital — Hillerød, Denmark (Recruiting)
• Hvidovre hospital — Hvidovre, Denmark (Recruiting)
• Zealand University Hospital — Køge, Denmark (Recruiting)
• Steno Diabetes Center Odense — Odense, Denmark (Recruiting)

Study contacts

• Study coordinator: Ole Lander Svendsen, MD

Conditions Charcot Foot; Diabetes Mellitus