An Open Label study of the drug denosumab in acute Diabetes Charcot’s Neuroarthropathy.
- Conditions
- Diabetes MellitusCharcot Neuropathic OsteoarthropathyMusculoskeletal - Other muscular and skeletal disordersMetabolic and Endocrine - DiabetesNeurological - Other neurological disorders
- Registration Number
- ACTRN12614000326695
- Lead Sponsor
- South Western Sydney Local Health District
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 36
Type 1 or Type 2 diabetes
Diabetic peripheral neuropathy
1. Pregnant women or women of child-bearing age not using contraception
2. Women who are breastfeeding
3. Peripheral vascular disease – confirmed by clinical history PLUS absence of two or more foot pulses or an ankle brachial index of <0.8 (see below)
NB: Patients with known PVD and who have undergone successful revascularization as determined by clinical history PLUS palpable pulses PLUS bi- or tri -phasic Doppler wave forms are NOT excluded.
4. Foot ulceration > Texas classification 1A
NB: A foot ulcer with Texas classification grade 1A has met inclusion criteria in previous studies of acute CN.
5. Cellulitis and/or osteomyelitis of the affected foot (clinically and/or radiologically proven)
6. Previous midfoot or proximal to mid foot amputation
7. Hypocalcaemia (Serum Calcium <2.1 mmol/L)
8. Vitamin D deficiency (Serum 25-hydroxyvitamin D <30 nmol/L)
9. History of hypoparathyroidism or pending thyroid or parathyroid surgery
10. Poor oral hygiene, which is defined as:
*Within 3 months of a tooth extraction, dental implants or mandibular surgery
*Within 6 months of planned tooth extraction, dental implants or mandibular surgery
*Presence of multiple (more than 3) dental caries
NB: Previous dental clearance and the use of a dental plate(s) are NOT contra-indication for enrollment
NB: This is because osteonecrosis of the jaw (ONJ) has been reported in patients treated with Denosumab.
11. Renal failure (serum creatinine >200 mmol/L or eGFR< 30 ml/min).
12. 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 2xULN
13. History of decompensated congestive heart failure
14. History of inflammatory arthopathies (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, autoimmune arthopathy)
15. History of inflammatory bowel disease (Crohn’s disease, Ulcerative Colits, other inflammatory colitis)
16. Any history of treatment with Denosumab within the last 12 months.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Time from the first injection at which the temperature differential at the site of maximum deformity and maximum temperature on the affected foot or ankle becomes < 2 degrees Celsius compared to the similar site on the contra-lateral foot or ankle, measured using an infrared thermometer. <br><br>[The primary endpoint of temperature difference is measured at screening, zero time (injection), one week, two weeks, four weeks, six weeks, eight weeks, ten weeks, twelve weeks, fourteen weeks, sixteen weeks, twenty weeks, twenty two weeks, six months, nine months and twelve months. ]
- Secondary Outcome Measures
Name Time Method Disease activity will be measured by the appropriate inflammatory markers (ESR, CRP TNF-alpha, IL-6), bone turn over markers (serum CTX, P1NP, urine: CTX: creatinine ratio and DPD: creatinine ratio) and evidence of stability of radiological findings on plain x-ray. <br><br>[Inflammatory marker data for ESR and CRP will be captured at screening, week 2,3,5,7,9,11,14,15.<br><br>Bone turnover marker data will be captured at weeks 2,5,9.<br><br>Radiological examinations of bilateral feet (plain x-ray) will be taken at the screening visit, 6 months and 12 months.]