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Trial registered on ANZCTR


Registration number
ACTRN12614000326695
Ethics application status
Approved
Date submitted
3/03/2014
Date registered
26/03/2014
Date last updated
18/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
An Open Label study of the drug denosumab in acute Diabetes Charcot’s Neuroarthropathy.

Scientific title
A Two Part Phase II Open Label Study on the effects of Denosumab in modifying disease activity in patients with Diabetes Mellitus and Charcot Neuropathic Osteoarthropathy.

Secondary ID [1] 283439 0
Nil
Universal Trial Number (UTN)
U1111-1149-4197
Trial acronym
2 POD-C
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus 290349 0
Charcot Neuropathic Osteoarthropathy 290350 0
Condition category
Condition code
Metabolic and Endocrine 290746 290746 0 0
Diabetes
Musculoskeletal 291675 291675 0 0
Other muscular and skeletal disorders
Neurological 291844 291844 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study aims to seek evidence that RANKL blockade using the drug Denosumab can modify disease activity in Charcot Neuropathic Osteoarthropathy. The dose of Denosumab that will be administered is the same as current TGA approved for the treatment of osteoporosis in postmenopausal women and androgen deprived men. The dose is 60 mg administered subcutaneously in a single, one off injection. Follow up will last for 12 months.
Intervention code [1] 288157 0
Treatment: Drugs
Comparator / control treatment
This is a open labelled study with no comparison.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 290746 0
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.

Timepoint [1] 290746 0
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 [1] 305156 0
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.

Timepoint [1] 305156 0
Inflammatory marker data for ESR and CRP will be captured at screening, week 2,3,5,7,9,11,14,15.

Bone turnover marker data will be captured at weeks 2,5,9.

Radiological examinations of bilateral feet (plain x-ray) will be taken at the screening visit, 6 months and 12 months.

Eligibility
Key inclusion criteria
Type 1 or Type 2 diabetes
Diabetic peripheral neuropathy
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
36 partcipants will be enrolled into this pilot study. The study is a necessary precursor to an adequately powered randomized placebo-controlled study of Denosumab in active CN, as it will establish the sample size and feasibility of such a study.

The changes in temperature and inflammatory markers will be collected.

Descriptive statistics will be calculated appropriate to the data.

Comparisons with results in the published literature will be made as appropriate.

All analyses will be done using the Statistical Package for Social Sciences (SPSS Inc., Chicago, Illinois, USA).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 1605 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 1606 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 8659 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 7480 0
2170 - Liverpool
Recruitment postcode(s) [2] 7482 0
3050 - Royal Melbourne Hospital
Recruitment postcode(s) [3] 16767 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 288157 0
Hospital
Name [1] 288157 0
South Western Sydney LHD
Liverpool Hospital
Address [1] 288157 0
Liverpool Hospital, Locked bag 7103, Liverpool, NSW 1871
Country [1] 288157 0
Australia
Primary sponsor type
Hospital
Name
South Western Sydney Local Health District
Address
South Western Sydney Local Health District
Liverpool Hospital, Locked bag 7103, Liverpool, NSW 1871
Country
Australia
Secondary sponsor category [1] 286879 0
Hospital
Name [1] 286879 0
Victoria Health
The Royal Melbourne Hospital
Address [1] 286879 0
The Royal Melbourne Hospital
4 West Grattan St, Parkville, Victoria 3050
Country [1] 286879 0
Australia
Secondary sponsor category [2] 286880 0
Hospital
Name [2] 286880 0
Queensland Health
The Prince Charles Hospital
Address [2] 286880 0
The Prince Charles Hospital,
Rode Road, Chermside,
QLD 4032
Country [2] 286880 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290073 0
South Western Sydney Local Health District Human Research ethics Committee
Ethics committee address [1] 290073 0
Ethics and Research Governance Office, SWSLHD Locked Bag 7017, LIVERPOOL BC, NSW, 1871
Ethics committee country [1] 290073 0
Australia
Date submitted for ethics approval [1] 290073 0
07/10/2013
Approval date [1] 290073 0
09/01/2014
Ethics approval number [1] 290073 0
HREC/13/LPOOL/457

Summary
Brief summary
We aim to explore if the drug ‘denosumab’ is effective at reducing bone loss in the feet/foot in participants with Diabetes Mellitus and Charcot Foot. Bone loss or Osteoponia as it is referred to medically is a recognised feature of Charcot foot. If the bone loss process can be prevented then this may stop the Charcot process in a much quicker time frame.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 43790 0
Dr Namson Lau
Address 43790 0
Liverpool Hospital
Department of Diabetes and Endocrinology
Goulburn Street
Liverpool
Locked bag 7103, Liverpool, NSW 1871
Country 43790 0
Australia
Phone 43790 0
+61 2 873 87175
Fax 43790 0
Email 43790 0
namson.lau@sydney.edu.au
Contact person for public queries
Name 43791 0
Mr Matthew Malone
Address 43791 0
Liverpool High Risk Foot Service, Clinic 112
South Western Sydney Local Health District
Liverpool Hospital, Locked bag 7103, Liverpool, NSW 1871
Country 43791 0
Australia
Phone 43791 0
+61 2 873 87175
Fax 43791 0
Email 43791 0
matthew.malone@health.nsw.gov.au
Contact person for scientific queries
Name 43792 0
Prof Hugh Dickson
Address 43792 0
Department of Ambulatory Care
Liverpool Hospital
Locked bag 7103, Liverpool, NSW 1871
Country 43792 0
Australia
Phone 43792 0
+61 2 8738 8089
Fax 43792 0
Email 43792 0
hugh.dickson@health.nsw.gov.au

No data has been provided for results reporting
Summary results
Not applicable