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Trial registered on ANZCTR


Registration number
ACTRN12617001414303
Ethics application status
Approved
Date submitted
3/08/2017
Date registered
6/10/2017
Date last updated
6/10/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Insulin treatment for diabetic foot ulcers
Scientific title
Does intensive glycaemic control promote healing in diabetic foot ulcers? A feasibility
study
Secondary ID [1] 292578 0
Nil
Universal Trial Number (UTN)
UTN: U111111634770
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes 304244 0
Diabetic foot ulcer 304245 0
Condition category
Condition code
Metabolic and Endocrine 303597 303597 0 0
Diabetes
Skin 303824 303824 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Substudy 1 - Entry criteria and treatment acceptability.
Study design: Cross-sectional study (no follow-up). Target Feasibility Issues: 1 and 2
Accrual period: 24 weeks
Participants: All patients 18 years of age or over with diabetes and a current foot ulcer presenting at the CMH Multidisciplinary Diabetes Foot Clinic during the study period will be invited to participate.
Main entry criteria: Incident ulcer, as determined from patient history and inspection at the clinic.
Outcomes: Fulfillment of each full study entry criterion (dichotomous); DiabMedSat (diabetes medications satisfaction questionnaire) sub scores.
Assessments: For each participant consenting by signing a patient information sheet to substudy 1, a delegated member of the research team will record demographic data and study entry criteria status and patients will be invited to complete a diabetes patient satisfaction questionnaire (DiabMedSat). Their foot wound will be inspected which is a routine procedure of every patient attending the clinic. Demographic and other clinical data would already be available on electronic patient data base and patient clinical records.

Substudy 2
Study design: Single-arm prospective study; Target feasibility issues: 2 to 6
Accrual period duration: 16 weeks; Intervention and follow-up period duration: 24 weeks
Participants: Twenty adult patients with diabetes and foot ulcer attending the CMH Multidisciplinary Diabetes Foot Clinic.
Main entry criteria: All patients who have participated in Substudy 1 and meet study inclusion/exclusion criteria will be offered to participate in the Substudy 2 until the target sample size is reached. The patient information sheet for Substudy 2 will be discussed and patients given the option of taking it home to consider. They will be subsequently contacted and if willing to participate will attend visit 1 of this substudy. At this visit the informed consent of patients will be obtained by a member of the study team after further clarifying their questions as needed. Study procedures are illustrated in the schedule attached .We intend to recruit 20 patients spread over 16 weeks from commencement of the trial.
Patients recruited for substudy 2 would be assessed by the podiatrist (vascular status by toe pressure measurements, digital photographic planimetry of the ulcer/ulcers and microcirculation by laser speckled imaging technique) and then receive relevant usual treatment including ulcer debridement, organisation of proper orthotics, treatment of infection if needed etc. Except for digital photographic imaging, laser speckled imaging and completing questionnaires, the treatment consists in routine care. Visits 1-4 will be weekly, visits 5-6 fortnightly and visits 7-9 monthly. If additional visits are required for extra debridement they will be arranged as required.
Dose Adjustments : Either the diabetes nurse specialist or the medical doctor or both will comprehensively assess the patient’s glycaemic status on the basis of the patients monitoring records and either instigate insulin therapy or upgrade treatment of existing insulin therapy.
Intervention: Our proposed intervention is an 11-week intensive insulin therapy programme. Insulin will be administered in addition to oral hypoglycaemic tablet therapy consistent with International Guidelines (International Diabetes Federation; Global guideline for type 2 diabetes). Either intermediate acting insulin or long acting insulin will be started (in patients who are not on insulin) or adjusted (in patients who are already on insulin) and short acting meal time insulin will be added in relevant cases to improve glycaemic profile. All participants will be expected to perform routine home blood glucose monitoring and maintain regular telephone contact with the principal investigator and/or the diabetes nurse specialist for dose adjustment and stabilisation advice using a treat-to-target approach for insulin dose adjustment. Participants will be contacted by telephone at least twice weekly for dose adjustment advice .The treatment targets are capillary blood glucose (CBG) levels of 4-7 mmol/L before meals and <10 mmol/L after meals, no more than 2 episodes of mild hypoglycaemia per week, and HbA1c either equal to or less than <53 mmol/mol (<7.0%). Adherance to treatment regime will be assessed by reviewing blood glucose monitoring records.
Intervention code [1] 298795 0
Treatment: Drugs
Comparator / control treatment
No Control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302962 0
Substudy 1:
Estimate the proportion of foot clinic patients who satisfy potential inclusion/exclusion criteria by reviewing clinic records and screening potential patients.

Timepoint [1] 302962 0
Substudy 1 - At visit one

Primary outcome [2] 303186 0
Substudy 2:
Composite outcome: Estimate the distribution of rate of healing and time to healing of foot ulcers under an intervention of glycaemic control utilising Digital Photographic Planimetry (silhouette of incident ulcer area) . This is a three dimensional photographic assessment looking at depth, width and breadth of the wound.
Timepoint [2] 303186 0
Substudy 2 - weekly for the first four visits and fortnightly for the next 2 visits, then monthly for the next 4 visits.
Secondary outcome [1] 337576 0
Substudy 1:
Estimate satisfaction with diabetes medications in a diabetic population presenting for podiatry care by utilising a diabetes medication satisfaction questionnaire.



Timepoint [1] 337576 0
Substudy 1: At visit 1

Secondary outcome [2] 338175 0
Substudy 2:
- Estimate acceptability of intensive insulin therapy in a diabetic population presenting for podiatric care utilizing the Diabetes Medication Satisfaction Questionnaire.



Timepoint [2] 338175 0
Substudy 2:
At visits 2 through to and including visit 10
Secondary outcome [3] 338176 0
Substudy 2:
Capillary blood glucose (CBG) measured using finger prick a glucose montitoring device.
Timepoint [3] 338176 0
Visit 1 to 10 inclusive.
Secondary outcome [4] 338584 0
HbA1c - measured using finger prick to obtain blood and read in a DCA vantage machine.
Timepoint [4] 338584 0
Weeks 1,16,24
Secondary outcome [5] 339465 0
Toe pressure/ABI (ankle brachial index) to confirm peripheral arterial disease.
Timepoint [5] 339465 0
Baseline and week 24
Secondary outcome [6] 339466 0
Laser speckled imaging technique using a laser speckled device (New device designed by Auckland Biomedical engineering department), measuring micro-circulation of the foot. This new device creates a superficial perfusion index of the plantar surface and is used to assess the effect of the intervention on progression of the micro-circulatory status.
Timepoint [6] 339466 0
Visits 1 to 10 inclusive

Eligibility
Key inclusion criteria
Substudy 1: All patients 18 years of age or over with diabetes and a current foot ulcer presenting at the CMH Multidisciplinary Diabetes Foot Clinic during the study period will be invited to participate.

Substudy 2:
Proposed Inclusion Criteria for the intended full study (Feasibility Issue)
1. Male or female aged 18 to 90 years
2. Type 1 or type 2 diabetes mellitus for more than 1 year with an HbA1c >58 mmol/mol (7.5%).
3. Incident foot ulcer(s) located below the level of malleoli.
4. Able and willing to undertake home blood glucose monitoring and administer insulin up to 4 times daily under the supervision of a diabetes nurse specialist.
5. Able to provide informed consent to participate in the study.
Minimum age
18 Years
Maximum age
90 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Proposed Exclusion Criteria for the intended full study (Feasibility Issue)
1. Ulcers with clinically significant deep tissue infection.
2. Significant peripheral vascular disease under consideration for re-vascularisation.
3. Significant bony deformity which may delay wound healing.
4. Non-compliance with standard care.
5. Any other disease or condition which in the opinion of the investigator could make them unsuitable for entry.


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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Substudy 1:
Statistical analysis plan: Descriptive statistics of the reasons for potential screen failures will be produced by demographic characteristics and by categorised treatment regimen. Potential recruitment rates based on different configurations of entry criteria and their demographic profiles will be produced to inform selection of final entry criteria for the full study. Descriptive statistics of the DiabMedSat subscores and overall scores will be produced. The recruitment log of Substudy 2 will be used to estimate consent rates amongst eligible patients along with 95% confidence intervals based on a negative binomial distribution.

Substudy 2:
CBG will be used as a proxy for compliance and regressed first on the DiabMedSat items, then on the DiabMedSat sub scores, to determine areas of compliance intervention (issue 2). CBG and DiabMedSat sub scores will also be used to predict non-adherence and drop-outs, although the main result here will be the raw attrition rate from Substudy 2 (issue 3). Convergent validity for each of the competing primary outcomes will be assessed through correlation with DFS-SF, and sensitivity to HbA1c of each established through (mixed) linear or Cox (frailty) regression. Mixed/frailty models may allow the estimation of intra-participant correlation for both outcomes, dependent on the prevalence of multiple ulcers (issue 4). The outcome characteristics obtained (mean standard deviation; observed rate, observed censoring proportion) will inform a final full study size computation (issue 5). Issue 6 will be resolved through acquisition of the data and establishment of registration and data management procedures adapted to co-registered perfusion and ulcer maps.

Recruitment
Recruitment status
Completed
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 outside Australia
Country [1] 9124 0
New Zealand
State/province [1] 9124 0
Auckland

Funding & Sponsors
Funding source category [1] 297155 0
Government body
Name [1] 297155 0
Health Research Council
Address [1] 297155 0
50 Grafton Road, Grafton, Auckland 1010
Country [1] 297155 0
New Zealand
Primary sponsor type
Individual
Name
Dr Ajith Dissanayake
Address
Middlemore Hospital
100 Hospital Rd
Papatoetoe
Auckland 2025
Country
New Zealand
Secondary sponsor category [1] 296170 0
None
Name [1] 296170 0
Address [1] 296170 0
Country [1] 296170 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298322 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 298322 0
PO Box 5013
Wellington
6011
Ethics committee country [1] 298322 0
New Zealand
Date submitted for ethics approval [1] 298322 0
30/10/2014
Approval date [1] 298322 0
13/11/2014
Ethics approval number [1] 298322 0
14/NTA/195

Summary
Brief summary
The purpose of this study is to determine the feasibility of conducting a full length trial to determine the effects of intensive insulin treatment on the control of blood sugar and whether this improves healing of foot ulcers in patients with diabetes. It is expected that improved control of blood sugar will also improve healing of foot ulcers and result in reduced infection and amputation rates due to ulcers that have not healed. Blood flow through the small vessels in the foot will be measured and the rate that the ulcers shrink and heal will be recorded. The study is split into two parts, substudy 1 and substudy2.
Trial website
Trial related presentations / publications
Pending
Public notes

Contacts
Principal investigator
Name 76714 0
Dr Ajith Dissanayake
Address 76714 0
Middlemore Hospital
100 Hospital Rd
Papatoetoe 2025
Country 76714 0
New Zealand
Phone 76714 0
+64 9 2760000
Fax 76714 0
+64 9 250 3878
Email 76714 0
amdiss@middlemore.co.nz
Contact person for public queries
Name 76715 0
Dr Ajith Dissanayake
Address 76715 0
Middlemore Hospital
100 Hospital Rd
Papatoetoe 2025
Country 76715 0
New Zealand
Phone 76715 0
+64 9 2760000
Fax 76715 0
+64 9 250 3878
Email 76715 0
amdiss@middlemore.co.nz
Contact person for scientific queries
Name 76716 0
Dr Ajith Dissanayake
Address 76716 0
Middlemore Hospital
100 Hospital Rd
Papatoetoe 2025
Country 76716 0
New Zealand
Phone 76716 0
+64 9 2760000
Fax 76716 0
+64 9 250 3878
Email 76716 0
amdiss@middlemore.co.nz

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary