Denosumab for Acute Charcot foot (Charcot neuroarthropathy) in diabetes

Inclusion criteria

• {"criterion_text":"- Age 18-80 years AND Type 1 or type 2 diabetes (diagnosed diabetes for more than 3 months) AND 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 and\t 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

• {"criterion_text":"- •\tDuration of the acute Charcot foot for more than 3 months (at the screening visit). •\tExisting foot ulcer on the affected foot, unless the ulcer is very superficial, in healing and with no signs of infection and no increased surrounding skin temperature compared to the contralateral foot. •\tPrevious acute or chronic Charcot of the affected foot •\tPlanned surgery on the acute Charcot foot •\tInfection (cellulitis or osteomyelitis) of the affected foot (clinically and/or radiologically proven) •\tPrevious midfoot or proximal to mid foot amputation of the affected foot •\tHypocalcemia (Serum Calcium <2.1 mmol/L or Calcium ion < 1.12 mmol/L) •\tVitamin D deficiency (Serum 25-hydroxyvitamin D < 50 nmol/L) •\tRenal failure (serum creatinine >200 mmol/L or eGFR < 30 ml/min). •\tTreatment with Denosumab within the last 12 months. •\tHave a known hypersensitivity to Denosumab •\tHistory of osteonecrosis of the jaw. •\tPoor oral hygiene, which is defined as within 3 months of a tooth extraction, dental implants or mandibular surgery •\tPlanned mandibular surgery or dental implants within the next 12 months. •\tPrior non-traumatic vertebral fracture •\tTreatment 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) •\tActive 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 •\tHistory of inflammatory arthropathies (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, autoimmune arthropathy) •\tPre-existing medical condition judged to preclude safe participation in the study •\tCurrent treatment with cytotoxic drugs or with systemically administered glucocorticoids •\tAbuse of alcohol or drugs, or presence of any condition that in the Investigators opinion may lead to poor adherence to study protocol •\tPregnancy, 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). •\tLikely inability to comply with the visits because of planned activity •\tUse of any investigational product with the last month. •\tUse 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. •\tCancer, 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"}

Primary endpoints

• {"endpoint_text":"- Time from first injection of IP until the time point where the acute Charcot foot is clinically healed/in remission, ie. the temperature difference at the site maximum temperature on the affected Charcot foot is < 2 degrees Celsius compared to the similar site on the contra-lateral foot, measured using an infrared thermometer, and edema and redness of the skin has subsided – at two subsequent visits 4 weeks apart.","definition_or_measurement_approach":"Defined as time from first injection until clinical healing/in remission: temperature difference < 2°C compared to contra-lateral foot measured using an infrared thermometer, and edema and redness subsided, confirmed at two subsequent visits 4 weeks apart."}

Secondary endpoints

• {"endpoint_text":"- Fraction of clinical healed participants at each study visit. Fraction of healing on X-rays and MRI (or PET/CT or Scintigram) at the time of clinical healing and at the End of trial. Number of relapses (defined as need for/prescription of off- loading with cast of the Charcot foot again) ...","definition_or_measurement_approach":"Includes fraction of clinically healed participants at each visit; imaging-based fraction of healing on X-ray/MRI/PET-CT/Scintigram at clinical healing and end of trial; number of relapses defined as need for/prescription of off-loading with cast."}

Denmark

Earliest CTIS Part Ii Submission Date

24-06-2024

Latest Decision Or Authorization Date

18-03-2026

Processing Time Days

632

Number Of Sites

8

Number Of Participants

114

Primary sponsor

Full Name

Region Hovedstaden

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"code:1","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"code:1","organisation_type":"Hospital/Clinic/Other health care facility"}