Effects of a single denosumab injection on reduction of total contact cast treatment and consolidation of bonefractures caused by acute Charcotfoot in patients with diabetes mellitus (CHARCOT study)

Previous research has shown 0.1-5% of all subjects with diabetes mellitus and
concomitant neuropathy develop a Charcot foot , which is a sterile inflammation
driving increased osteoclastic actictivity within the bones in the foot. This
results in spontaneous and painful fractures of these bones with subsequent
deformation of the foot and increased risk of ulcer formation and lower leg
amputation. Besides long term treatment with total contact casts (TCC) boot of
the affected leg, no treatment is available despite the fact that Charcot foot
is associated with increased morbidity and reduced quality of life (not able to
work or drive a car and limitied movement due to total contact cast). Although
the pathophysiology is largely unknown, a study using bonebiopsies showed
increased production of RANKL in the affected bones of the Charcot foot. In the
last few years, a subcutaneously injectable RANKL antibody (denosumab) was
registered for the treatment of osteoporosis. We therefore would like to
investigate whether denosumab compared to saline placebo has a beneficial
effects on bonefracture healing and preventing deformation of the foot in
patients with Charcot foot.

This study has been transitioned to CTIS with ID 2024-518637-28-00 check the CTIS register for the current data.

Does single subcutaneous injection with denosumab or placebo (NACL 0.9%)
induces a shorter Total contact cast treatment duration and faster bonefracture
healing (days) and does it prevent deformation of the foot in patients with
Charcot foot

single center randomized dubbel blinded placebo controlled study

one 1ml of either denosumab 60mg or 1 ml NACL 0.9% subcutaneous injection

Patients will receive one injection with an already registered studydrug
(denosumab) or placebo (NACL 0.9%), which can induce temporary discomfort
(bruises and muscle aches) . The only side effects known to date of denosumab
are itching after injection and temporary gastrointestinal side effects (often)
and very rarely osteonecrosis of the jaw upon dental treatment (molar
extraction). Subjects are therefore advised not to participate if they have
molar extraction planned and cannot undergo this treatment in first year after
treatment. Nevertheless the overall risk of this studydrug is low. After
injection, patient will be treated according to standard clinical care protocol
including daily intake of caclichew tablets (for optimalisation of Calcium and
vitamin D) as well as the same routine visits (weekly TCC changes and monthly
clinic vists including temperature and foot volume measurements and (standing)
x-ray of the affected foot until consolidation of the bonefractures is
observed). Two extra visits to AMC are requested for 1) for informed consent by
PI and baseline bloodsample + injection and 2) bloodsample at end of study.