Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05797259 |
| Other study ID # |
DANCN 01 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
March 10, 2019 |
| Est. completion date |
March 31, 2023 |
Study information
| Verified date |
August 2023 |
| Source |
Postgraduate Institute of Medical Education and Research |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This study's goal was to determine how denosumab 60 mg, combined with total contact casting
and restricted weightbearing status, would affect the treatment of acute CN with CKD.
METHODS Participants in the research were those who visited the outpatient foot clinic at
PGIMER, CHD in India. During the study period, 446 persons with CN were identified, 102 of
whom met the criteria for the first screening, and 78 of whom were ultimately enrolled in the
study.
Aim: To assess the clinico-radiological remission of Acute Charcot-neuroarthropathy in
patients of CKD.
Description:
Participants attending the outpatient diabetic foot facility of tertiary care hospital in
North India were assessed for active CN. An active CN of the foot was considered in the
presence of localised erythema, edoema, and a temperature differential of more than 20C
compared to a similar location on the opposite foot. Participants were diagnosed with "active
on chronic" CN if they met the requirements for active CN in the context of foot deformities
suggestive of chronic CN (rocker bottom deformity). Those with self-reported diabetes or
those who were already receiving treatment for diabetes, with an estimated glomerular
filtration rate (eGFR) <60 ml/min/m2 (CKD-EPI equation) and more than 500 mg of urine
protein/24 hours were considered as having diabetic CKD. Patients with active pedal ulcer,
inactive charcot foot, peripheral vascular disease (ankle brachial index ABI <0.9), prior
exposure to medications affecting bone metabolism particularly bisphosphonates, teriparatide,
denosumab or steroids in the past 12 months, hypocalcemia, active malignancy, CKD on dialysis
and pregnancy or lactating women were excluded. The study was conducted in accordance with
the Declaration of Helsinki and its amendments, the International Conference on Harmonization
Good Clinical Practice guidelines, and its applicable regulatory requirements. All
participants provided their signed, fully informed consent and study protocol was approved by
the institutional Ethics Committee ref INT/IEC/SPE-1664.
The foot temperature was determined by an infrared dermal thermometry [(FLIR Systems Inc,
Orlando, USA) with a pixel resolution of 4800 (80*60), thermal sensitivity of 0.15 C, and a
detection range of -20 C to 250 C] after 30 minutes of removing footwear or cast. X-ray
and/or magnetic resonance imaging (MRI) were used to confirm the diagnosis of an active CN
(3T scanner Siemens MagnetromVerio). The involved area of foot was classified anatomically
for pattern of involvement using the Sanders-Frykberg classification. Clinical information
was documented, including the duration of the symptoms, duration of diabetes, concomitant
microvascular and macrovascular complications. Comprehensive neurological testing included
vibration perception threshold (VPT>25 mV was considered abnormal) by
biothesiometer-Vibrometer-VPT1 (Diabetik Foot Care, Madras Engineering Service, India),
perception of 10-g monofilament at 5 standardised plantar locations, and ankle reflex.
Interventions:
Participants were randomly assigned in 1:2 ratio to receive either injection denosumab 60 gm
(Group A) or equal volume of normal saline (Group B) subcutaneous over abdomen as a single
dose (denosumab and normal saline were provided in similar looking syringe). The investigator
administering the treatment, radiologist and the patient were blinded to treatment
allocation. A conventional below knee, non-walking, non-removable fibreglass total contact
cast (TCC) were provided to all participants irrespective of the group allocation for
offloading.
Procedures:
Participants visited the study site initially during screening, randomization and
subsequently four weekly for the monitoring of foot temperature. During randomization visit,
blood samples were drawn for HbA1c, renal functions, calcium, phosphate and vitamin D. An
average of three temperature readings at the afflicted site of the foot were taken and
temperature difference (0C) were noted. The study drug or placebo were administered by
blinded investigator and TCC was provided. Subsequently, during 4-weekly follow up visits the
cast was removed for 30 minutes and skin temperature (mean of three readings) difference was
noted. A change of cast was performed four weekly or earlier to avoid "pistoning" effect
caused by the edema diminution until clinical remission. Patients with vitamin D deficiency
(25 (OH)D3<30 ng/ml were supplemented with weekly oral cholecalciferol 60,000 IU for 8 weeks
, then monthly till end of follow up.
A temperature difference of <2C between the afflicted foot and a similar site on the other
foot documented twice (four weeks apart) along with the absence of signs of inflammation was
considered "clinical remission" of active CN.
Following the clinical remission of active CN, the TCC shall be discontinued, and
participants received cast walkers or customised footwear. Subsequently, foot examination
shall be performed to monitor for the recurrence of CN (foot temperature assessment), the
occurrence of deformities or ulcers (clinical examination), new-onset fractures (radiological
assessment)or amputation for a minimum duration of 48 weeks following remission.
