Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001711101
Ethics application status
Approved
Date submitted
8/07/2019
Date registered
4/12/2019
Date last updated
4/12/2019
Date data sharing statement initially provided
4/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
An Evaluation of the association between High Density Lipoprotein (HDL) levels and functionality with the rate of wound healing in diabetic and non-diabetic patients.
Scientific title
An Evaluation of the association between High Density Lipoprotein (HDL) levels and functionality with the rate of wound healing in diabetic and non-diabetic patients.
Secondary ID [1] 298676 0
None
Universal Trial Number (UTN)
U1111-1236-6834
Trial acronym
HDL-DFW2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic foot ulcer healing 313574 0
Condition category
Condition code
Skin 312007 312007 0 0
Normal skin development and function
Metabolic and Endocrine 313718 313718 0 0
Diabetes

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This study will determine the association between circulating HDL cholesterol levels and functionality and the rate of wound closure in diabetic and non-diabetic patients.

Blood samples (20 mL) will be taken at the time of recruitment (baseline) then at 2 weeks, 6 weeks, 6 months and 12 months post-amputation (5 blood samples in total/participant). Wound biopsies (3mm2) will be collected at the time of amputation and then 4 weeks post-ampuation. Changes in wound area using a 3D camera and digital planimetry will be assessed monthly.

The total duration of observation per paticipant is 12 months.
Intervention code [1] 314945 0
Not applicable
Comparator / control treatment
We are using a healthy age-matched control group that have no wounds and are non-diabetic. A single blood sample will be taken from this cohort and HDL cholesterol levels and functionality will be assessed and compared to the diabetic and non-diabetic wound cohorts
Control group
Active

Outcomes
Primary outcome [1] 320651 0
Percentage wound closure from baseline wound area as measured using a 3D camera and digital planimetry.
Timepoint [1] 320651 0
Sixteen weeks post- minor amputation
Primary outcome [2] 322154 0
HDL cholesterol levels at the time of minor ampuation (baseline) as measured in the plasma using standard laboratory kits.
Timepoint [2] 322154 0
At the time of minor amputation (baseline)
Secondary outcome [1] 372328 0
Amputation free survival as assessed by record keeping during the follow-up visits over a 12-month period.
Timepoint [1] 372328 0
Assessed weekly for the first 6 weeks and then monthly until 6 months with a final 12 month visit post-minor amputation.
Secondary outcome [2] 377521 0
Anti-inflammatory effects of HDL as assessed ex vivo using cultured endothelial cells.
Timepoint [2] 377521 0
Assessed at the time of minor amputation (baseline), then 2 weeks, 6 weeks, 6 months and 12 months post-minor amputation.
Secondary outcome [3] 377522 0
Pro-angiogenic effects of HDL as assessed ex vivo using cultured endothelial cells.
Timepoint [3] 377522 0
Assessed at the time of minor amputation (baseline), then 2 weeks, 6 weeks, 6 months and 12 months post-minor amputation.
Secondary outcome [4] 377523 0
Wound inflammation markers (IL-1B, CCL2, TNF-alpha and IL-6) in wound biopsies using quantitative PCR.

This is an exploratory outcome.
Timepoint [4] 377523 0
At the time of minor ampuation and four weeks post- minor amputation.
Secondary outcome [5] 377524 0
Wound angiogenesis markers (VEGF, HIF-1 alpha and PDK4) in wound biopsies using quantitative PCR.

This is an exploratory outcome.
Timepoint [5] 377524 0
At the time of minor amputation and then four weeks post- minor amputation.

Eligibility
Key inclusion criteria
Consenting men and non-pregnant women. For diabetic patients: (Type I and II), HbA1c<12%, eGFR >15 mL/min/1.73m2 and not on dialysis with recent ray amputation. For non-diabetic patients: recent ulcer on the forefoot and on the dorsal side. For both diabetic and non-diabetic patients: no signs of active infection and evidence of adequate perfusion (>40 mm/Hg toe cuff pressure). Lipid drugs (e.g. statins, ezetimibe) are allowed. For healthly donor controls must be age-matched and be non-diabetic with no ulcers.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Elevated liver enzymes (>50 units AST, >56 units ALT), stroke or transient ischaemic attack within 3 months, heart failure, cancer with ongoing treatment or prognosis of <5 years, active inflammation, history of pancreatitis, DVT or pulmonary embolism, organ transplant, steroid therapy, hyperbaric treatment, dialysis, wound vacuum therapy, no history of Parkinson’s disease. Not deemed likely to require major leg amputation within 4 weeks or any obstacle to regular follow-up.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Study power: Based on an observational study that showed the incidence of lower extremity amputation is associated with low HDL-cholesterol levels, we predict that wound closure will be 25% greater in non-diabetic patients, compared to diabetic patients at 6 weeks. Sample size calculations are based on repeated measures ANOVA. A total of 54 patients (18 per group; 3 groups) will give 80% power to detect a difference in wound areas of 25% between diabetic and non-diabetic patients. Accounting for non-compliance/losses-to-follow-up of 10%, we aim to recruit 60 subjects (20/group). In the experience of Principal Investigator Prof Robert Fitridge, >90% continue clinic attendance after amputation.


Statistics
Pearson’s correlation test will be used to determine associations between HDL levels and functionality and the rate of wound healing. ANOVA will be used to compare differences in HDL functionality assessments between diabetic and non-diabetic patients with wounds as well as non-diabetic individuals without wounds.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
24/02/2020
Actual
Date of last participant enrolment
Anticipated
22/02/2021
Actual
Date of last data collection
Anticipated
1/03/2022
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 14157 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 14158 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 27127 0
5000 - Adelaide
Recruitment postcode(s) [2] 27128 0
5011 - Woodville

Funding & Sponsors
Funding source category [1] 303216 0
Charities/Societies/Foundations
Name [1] 303216 0
The Hospital Research Foundation
Country [1] 303216 0
Australia
Primary sponsor type
University
Name
The University of Adelaide
Address
North Terrace, Adelaide, South Australia, 5000
Country
Australia
Secondary sponsor category [1] 303230 0
Hospital
Name [1] 303230 0
Royal Adelaide Hospital
Address [1] 303230 0
North Terrace, Adelaide, South Australia, 5000
Country [1] 303230 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303773 0
Central Adelaide Local Health Network
Ethics committee address [1] 303773 0
Citi Centre Building 11 Hindmarsh Square Adelaide South Australia 5000

Postal address: PO Box 287 Rundle Mall Adelaide SA 5000
Ethics committee country [1] 303773 0
Australia
Date submitted for ethics approval [1] 303773 0
08/07/2019
Approval date [1] 303773 0
28/08/2019
Ethics approval number [1] 303773 0
HREC/19/CALHN/349

Summary
Brief summary
Diabetes affects nearly one million Australians. In more than 80% of diabetics who develop foot ulcers, poor wound healing results in the need for lower limb amputation. There is currently no treatment available for wound healing. This study aims to identify whether there is an association between circulating HDL cholesterol levels and the rate of wound healing in diabetic and non-diabetic patients. Over the last five years it has become evident that the functionality of the HDL particle is more predictive of disease outcome than HDL cholesterol levels. We will therefore also test HDL functionality is a series of ex vivo assays established in our laboratory. This study seeks to understand the relationship between HDL and wound healing in diabetes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94750 0
Prof Robert Fitridge
Address 94750 0
Royal Adelaide Hospital
North Terrace, Adelaide, South Australia, 5000
Country 94750 0
Australia
Phone 94750 0
+61 0439 800 583
Fax 94750 0
Email 94750 0
[email protected]
Contact person for public queries
Name 94751 0
Christina Bursill
Address 94751 0
South Australian Health and Medical Research Institute
North Terrace, South Australia, Adelaide, 5000
Country 94751 0
Australia
Phone 94751 0
+61 0409677846
Fax 94751 0
Email 94751 0
[email protected]
Contact person for scientific queries
Name 94752 0
Christina Bursill
Address 94752 0
South Australian Health and Medical Research Institute
North Terrace, Adelaide, South Australia, 5000
Country 94752 0
Australia
Phone 94752 0
+61 0409677846
Fax 94752 0
Email 94752 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Clinical data only (not personal data)
When will data be available (start and end dates)?
The data will be made available after publication of the manuscript of this work. The data will be available for a period of 15 years.
Available to whom?
To people in the medical research community who provide a methodologically sound proposal, case-by-case basis at the discretion of Primary Sponsor.
Available for what types of analyses?
Wound healing meta analyses
How or where can data be obtained?
The data will be able to be obtained through email contact with Christina Bursill ([email protected]).


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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