CompletedPhase 2ACTRN12617000937314

Novel treatment of acute Charcot foot using the medication denosumab combined with immobilisation.

Effect of denosumab in acute Charcot neuropathic osteoarthropathy on inflammation and on bone health using calcaneal quantitative ultrasound: a phase II randomised controlled trial.


Sponsor

Garvan Institute of Medical Research

Enrollment

40 participants

Start Date

May 28, 2018

Study Type

Interventional

Conditions

Summary

Charcot foot affects patients with decreased nerve function in their feet, most often due to diabetes, and leads to significant bone deformity. The resulting deformity increases the risk of ulcers, infection and amputation. However, if detected early, this process may be prevented. Standard treatment currently involves using a cast or boot to minimise movement in the foot until inflammation resolves. We will investigate whether the addition of denosumab, a medication currently used for treating osteoporosis, reduces inflammation and bone loss in the foot. Bone loss will be monitored during treatment using a heel ultrasound machine. The potential clinical benefits may include a reduction in the length of time that a cast or boot is required, and reduction in the severity of bone deformity.


Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria5

  • Pre-existing diagnosis of diabetes mellitus
  • Ambulant
  • Willingness to provide written consent and to participate in study
  • Peripheral neuropathy confirmed with monofilament
  • Acute CN confirmed radiologically, significantly higher temperature in affected foot compared to contralateral foot (greater than 2 degrees Celsius maximal difference), and less than or equal to 3 months since symptoms onset

Exclusion Criteria13

  • Unable to provide informed consent
  • Previous or planned (within subsequent 18 months) osteotomy or surgical fixation involving the foot
  • Previous or planned (within subsequent 18 months) lower limb amputation above level of ankle
  • Non-weight bearing for greater than 2 month period during past year
  • Antiresorptive therapy during past 12 months, and/or greater than 5 year cumulative exposure
  • Pre-existing diagnosis of peripheral arterial disease, or impalpable pedal pulses
  • Heal ulceration at site of calcaneal quantitative ultrasound probe
  • Other acute foot disease: ulceration (>1A on Texas Classification) or infection
  • Vitamin D deficiency (25-hydroxyvitamin D < 50 nmol/L) if sufficiency cannot be rapidly achieved by supplementation
  • Hypocalcaemia (corrected calcium < 2.10 mmol/L)
  • Active dental infection, invasive dental procedure within preceding 3 months, planned invasive dental procedure within subsequent year, other dental contraindication to antiresorptive therapy
  • Women lactating, pregnant or of childbearing potential not using contraception
  • Life expectancy less than 2 years

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Interventions

Denosumab plus immobilisation. Denosumab 60 mg subcutaneously will be administered at baseline and then again after six months if clinical evidence of inflammation persists. The immobilisation devic

Denosumab plus immobilisation. Denosumab 60 mg subcutaneously will be administered at baseline and then again after six months if clinical evidence of inflammation persists. The immobilisation device (e.g. total contact cast, Aircast boot) will be applied by an appropriately qualified medical professional at the participant's recruitment site. Standard care and follow up of participants, including management of immobilisation, will be provided by the recruitment site. Immobilisation will be continued until resolution of acute Charcot neuropathic osteoarthropathy (CN).


Locations(8)

St Vincent's Hospital (Darlinghurst) - Darlinghurst

NSW, Australia

Blacktown Hospital - Blacktown

NSW, Australia

Nepean Hospital - Kingswood

NSW, Australia

Prince of Wales Hospital - Randwick

NSW, Australia

Royal North Shore Hospital - St Leonards

NSW, Australia

Royal Prince Alfred Hospital - Camperdown

NSW, Australia

St George Hospital - Kogarah

NSW, Australia

Westmead Hospital - Westmead

NSW, Australia

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ACTRN12617000937314