Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000675527
Ethics application status
Approved
Date submitted
15/05/2024
Date registered
28/05/2024
Date last updated
23/06/2024
Date data sharing statement initially provided
28/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
FOOT-C: Foot Ulcer Treatment with vitamin C.
Scientific title
Efficacy of vitamin C treatment to aid the healing of foot ulcers in people with diabetes: a randomised, placebo-controlled double-blind trial
Secondary ID [1] 312149 0
None
Universal Trial Number (UTN)
U1111-1308-1050
Trial acronym
FOOT-C
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes-related foot ulcer 333795 0
Condition category
Condition code
Metabolic and Endocrine 330466 330466 0 0
Diabetes
Skin 330544 330544 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
75 males and females with a diabetes-related foot ulcer will be recruited for this multi-site study and undergo placebo or vitamin C supplementation (oral ingestion of 500 mg ascobic acid per capsule, two capsules per day for eight weeks) in a double-blind, randomised manner. Patients will be provided with 8 weeks of either vitamin C or placebo capsules in identical opaque sealed bottles and adherence will be assessed via bottle returns. All researchers involved in the assessments and clinical care staff along with the patients will be blinded to the group allocation with all participants continuing to receive usual standard of care throughout the trial. All outcome measures will be conducted at the beginning (baseline) and then at eight weeks of treatment. Outcome measures for wound healing will also be recorded at fortnightly visits to the clinic during the eight week treatment period. The trial will conclude for each patient at eight weeks or beforehand if the ulcer has 100% healed or if the patient undergoes amputation or withdraws consent.
Intervention code [1] 328583 0
Treatment: Other
Comparator / control treatment
Participants in the control group will receive placebo microcellulose capsule twice daily
Control group
Placebo

Outcomes
Primary outcome [1] 338234 0
Percentage ulcer size healing
Timepoint [1] 338234 0
Baseline and after completion of 8 weeks of treatment.
Secondary outcome [1] 435083 0
Time to 50% ulcer healing
Timepoint [1] 435083 0
Baseline and every 2 weeks during the 8-week treatment.
Secondary outcome [2] 435084 0
Rate of ulcer healing
Timepoint [2] 435084 0
Baseline and every 2 weeks during the 8-week treatment.
Secondary outcome [3] 435085 0
Time to complete ulcer healing
Timepoint [3] 435085 0
Baseline and every 2 weeks during the 8-week treatment.
Secondary outcome [4] 435086 0
Blood glucose control (Exploratory outcome)
Timepoint [4] 435086 0
Baseline and immediately after the 8-week treatment.
Secondary outcome [5] 435087 0
Blood glucose control (Exploratory outcome)
Timepoint [5] 435087 0
Baseline and immediately after the 8-week treatment.
Secondary outcome [6] 435088 0
Blood glucose control (Exploratory outcome)
Timepoint [6] 435088 0
Baseline and immediately after the 8-week treatment.
Secondary outcome [7] 435089 0
Blood pressure (Exploratory outcome)
Timepoint [7] 435089 0
Baseline and immediately after the 8 week treatment.
Secondary outcome [8] 435090 0
Vitamin C status
Timepoint [8] 435090 0
Baseline and immediately after the 8-week treatment
Secondary outcome [9] 435091 0
Small arterial function in the periphery (Exploratory outcome)
Timepoint [9] 435091 0
Baseline and immediately after the 8 week treatment.
Secondary outcome [10] 435092 0
Blood lipid profile (Exploratory outcome)
Timepoint [10] 435092 0
Baseline and immediately after the 8-week treatment
Secondary outcome [11] 435093 0
Oxidative stress (Exploratory outcome)
Timepoint [11] 435093 0
Baseline and immediately after the 8-week treatment
Secondary outcome [12] 435094 0
Symptoms and signs of scurvy (Exploratory outcome)
Timepoint [12] 435094 0
Baseline and immediately after the 8-week treatment
Secondary outcome [13] 435095 0
Diabetes Distress (Exploratory outcome)
Timepoint [13] 435095 0
Baseline and immediately after the 8-week treatment
Secondary outcome [14] 435096 0
Quality of life (Exploratory outcome)
Timepoint [14] 435096 0
Baseline and immediately after the 8-week treatment
Secondary outcome [15] 435097 0
Depression (Exploratory outcome)
Timepoint [15] 435097 0
Baseline and immediately after the 8-week treatment

Eligibility
Key inclusion criteria
Adult patients (greater than or equal to 18years old) with either type 1 or type 2 diabetes who present to the high risk foot service with a current foot ulcer will be eligible to be included into the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(i) inability to provide informed consent; (ii) already being treated with a vitamin C supplement; (iii) already proceeding to amputation following first visit; (iv) hemochromatosis; (v) people on dialysis or proceeding to dialysis following first visit; (vi) injuries arising from prolonged hospitalization or immobility (i.e. pressure sores)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer with numbered containers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
To ensure a similar distribution of wound severity between treatments at baseline, participants will be stratified by site and by ulcer size (< 1000 mm3 or >1000 mm3) in random block sizes of two and four at each site and randomly assigned to treatment using a computer-generated random number sequence by an independent researcher in a 1:1 ratio.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size calculations:
We require 75 participants to commence the study in order to ensure sufficiently high power for our key outcome measures (see details below). This level allows us to account for a 15% participant drop-out, while ensuring a high power to detect any statistical significance of the treatment.
64 participants (N=32 per treatment group) will allow for the detection of the primary outcome measure of percentage of ulcer size healing after eight weeks of treatment:
The minimal clinically important difference is considered a 50% improvement in ulcer size after 8 weeks of treatment. Since SD values have not been published for this outcome measure we assume a large effect size using a Cohen’s d = 0.80 (a= 0.05, two-tailed), with the estimated power = 90%. To inform sample size calculations for future RCTs, exploratory outcome measures will also be collected at baseline and at the end of the treatment with estimated power for the following measures being between 27-61% (HbA1c, fasting glucose, systolic blood pressure, mental health and well-being surveys). Estimated power =99% for outcome measure of 50% increase in plasma vitamin C levels after 8 weeks of treatment (mean difference = 48 umol/l, SD = 19 umol/l) (a= 0.05, two-tailed). Thus, note that all secondary outcomes not related to ulcer healing (secondary outcomes 4 - 15) are considered exploratory outcomes.

Statistical analysis:
Continuous outcomes will be compared on an intention-to-treat basis using linear regression models, adjusted for stratification variables site and baseline ulcer size, and if relevant for any outcome also adjusted for baseline level. For other secondary outcomes, such as the time to 50% healing and time to complete healing outcomes we will conduct survival analysis, including Kaplan-Meier curves and Cox proportional hazards models (adjusted for site and baseline ulcer size). Multiple imputation by chained equations will be used to handle missing outcome data. Per-protocol analysis will also be performed on all participants who are >90% capsule compliant.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2024
Actual
Date of last participant enrolment
Anticipated
1/09/2025
Actual
Date of last data collection
Anticipated
24/11/2025
Actual
Sample size
Target
75
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26540 0
Dandenong Hospital- Monash Health - Dandenong
Recruitment hospital [2] 26541 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 42580 0
3175 - Dandenong
Recruitment postcode(s) [2] 42581 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 316510 0
Charities/Societies/Foundations
Name [1] 316510 0
Diabetes Australia
Country [1] 316510 0
Australia
Primary sponsor type
University
Name
Deakin University
Address
Country
Australia
Secondary sponsor category [1] 318691 0
None
Name [1] 318691 0
Address [1] 318691 0
Country [1] 318691 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315308 0
Monash Health Human Research Ethics Committee A
Ethics committee address [1] 315308 0
Ethics committee country [1] 315308 0
Australia
Date submitted for ethics approval [1] 315308 0
24/04/2024
Approval date [1] 315308 0
03/06/2024
Ethics approval number [1] 315308 0
108162

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 134286 0
Prof Glenn D Wadley
Address 134286 0
Deakin University, School of Exercise and Nutrition Sciences, 221 Burwood Highway, Burwood, Victoria, 3125
Country 134286 0
Australia
Phone 134286 0
+61 392446018
Fax 134286 0
Email 134286 0
[email protected]
Contact person for public queries
Name 134287 0
Glenn D Wadley
Address 134287 0
Deakin University, School of Exercise and Nutrition Sciences, 221 Burwood Highway, Burwood, Victoria, 3125
Country 134287 0
Australia
Phone 134287 0
+61 392446018
Fax 134287 0
Email 134287 0
[email protected]
Contact person for scientific queries
Name 134288 0
Glenn D Wadley
Address 134288 0
Deakin University, School of Exercise and Nutrition Sciences, 221 Burwood Highway, Burwood, Victoria, 3125
Country 134288 0
Australia
Phone 134288 0
+61 392446018
Fax 134288 0
Email 134288 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.