Diabetic Foot UlcerNCT05704075
Clinical and Mechanistic Study of Transverse Tibial Transport in Complex Foot Ulcers
A study testing Transverse Tibial Transport (TTT) and Conventional in people with Diabetic Foot Ulcer, run by Chinese University of Hong Kong.
Trial summary
TTT is a novel surgical technique that may potentially solve the long-standing deficit of seeking effective treatment for diabetic foot ulcers, decreasing the need for amputations and softening the socio-economic impact it brings. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Foot Ulcer
- What is being tested?
- Transverse Tibial Transport (TTT) and Conventional
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2023to 31 Jan 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults >18 years old
- Patients with a Wagner stage 4 Foot ulcer (partial foot gangrene)
- No active wound infection as confirmed by bacterial fluorescence imaging. (the Moleculight i:X, Smith and Nephew handheld device illuminates with 405nm violet light which causes bacteria to emit characteristic endogenous fluorescence signals that are visualised in real-time on the device's screen, allowing an objective measure of adequate surgical debridement)
- Biochemically confirmed diabetes with fasting plasma glucose ≥ 7.0 mmol/L, or a random plasma glucose ≥ 11.1 mmol/L or haemoglobin A1c (HbA1c) level ≥ 6.5%
- Triaged out for angioplasty/vascular bypass by the vascular surgeon
- Triaged out of reconstructive flap surgery by the microvascular surgeon
Who cannot join
- Uncontrolled sepsis
- Contraindications for applying an external fixator device in the tibia (overlying skin conditions, surgical hardware such as tibial nails, total knee prosthesis etc.)
- Severe medical comorbidities precluding safe anaesthesia (recent myocardial infarct, limited pulmonary function etc.)
- Mental or physical disability which may impair the ability to adhere to the intervention plan, e.g. severe dementia, psychosis etc.
- Recent revascularisation procedure (<12 weeks)
- Recent medication/intervention affecting cell proliferation (e.g. chemotherapy, radiotherapy etc.), radiotherapy etc.)
About this study
TTT is a novel surgical technique that may potentially solve the long-standing deficit of seeking effective treatment for diabetic foot ulcers, decreasing the need for amputations and softening the socio-economic impact it brings. This trial will be the world's first prospective RCT to verify the promising clinical studies on the clinical benefit of TTT in treating diabetic foot ulcers. In addition, blood samples from this study will allow us to study the various systemic circulating soluble factors in relation to neovascularisation, immunomodulation, and stem cell mobilisation. By taking the blood and various time points, we will better understand the complex interplay between various biomarkers. This GRF will allow us to obtain tissue samples to analyse the histological cellular changes after TTT surgery. It will provide us with more insight on how TTT works, as well as potentially helping us pinpoint the important changes and timeframes related to this intervention.
The PI, Co-Is and collaborators create a strong team of clinicians and scientists with a solid clinical and basic science track record. The team has published guidelines and surgical techniques in TTT and run several training cadaveric workshops teaching the TTT surgical technique to local orthopaedic surgeons. The team has also established a rat TTT model and published on TTT immunomodulation and neovascularisation in addition to other ongoing mechanistic experiments in animals.
This prospective multi-centre randomised controlled trial may act as the foundation for launching this cost-effective TTT surgery to regulate neovascularisation, neurogenesis, immunomodulation and mobilisation of MSCs for the treatment of various chronic conditions. Regenerative medicine is a multi-million dollar industry, and the potential use of TTT can result in a range of clinical applications not limited to DFUs.
- Conditions
- Diabetic Foot Ulcer
- Being tested
- Transverse Tibial Transport (TTT), Conventional
- Medical subject headings
- Diabetic Foot
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transverse Tibial Transport (TTT)Procedure or surgery
Transverse tibial transport is a novel adaptation of concepts used in distraction histogenesis. The most common use of this surgical principle is in bone lengthening surgery, which is a well-established surgical procedure by applying an external fixator to the bone, creating a corticotomy, and gradually lengthening the bone at the optimal rate of 0.5mm/12hrs. The biological mechanisms of distraction histogenesis involve activating signalling pathways such as cytokines Interleukin 1 and Interleukin 6, pro-inflammatory markers TNF alpha, pro-osteogenic TGF-beta, BMPs and pro-angiogenic factors VEGF and angiopoietin . TTT utilises the concept of distraction histiogenesis, but distraction is performed in the transverse plane instead of a longitudinal distraction. In addition, the period of distraction is coupled with a corresponding compression period and ultimately results in no net change in limb length.
ConventionalProcedure or surgery
Dressing + Negative Pressure Wound Therapy
| Study group | Role | What they receive |
|---|---|---|
| Control Group | Other | Conventional Treatment: Dressing + Negative Pressure Wound Therapy Receives: Procedure: Conventional |
| TTT Group | Experimental | Dressing + Negative Pressure Wound Therapy + Transverse Tibial Transport Receives: Procedure: Transverse Tibial Transport (TTT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Wound Size
Wound size will be measured using digital photography with standardised marker dots.
Measured: 0 month
Wound Size
Wound size will be measured using digital photography with standardised marker dots.
Measured: 1 month
Wound Size
Wound size will be measured using digital photography with standardised marker dots.
Measured: 3 month
Wound Size
Wound size will be measured using digital photography with standardised marker dots.
Measured: 6 month
Wound Size
Wound size will be measured using digital photography with standardised marker dots.
Measured: 12 month
Secondary outcomes (46)
Foot Function
Foot function will be objectively measured using our validated Chinese Foot and Ankle Outcome Score or the original English version.
Measured: 0 month
Foot Function
Foot function will be objectively measured using our validated Chinese Foot and Ankle Outcome Score or the original English version.
Measured: 1 month
Foot Function
Foot function will be objectively measured using our validated Chinese Foot and Ankle Outcome Score or the original English version.
Measured: 3 month
Foot Function
Foot function will be objectively measured using our validated Chinese Foot and Ankle Outcome Score or the original English version.
Measured: 6 month
Foot Function
Foot function will be objectively measured using our validated Chinese Foot and Ankle Outcome Score or the original English version.
Measured: 12 month
Incidence of Amputation
Incidence of Amputation
Measured: Up to 52 weeks
Ankle Brachial Pressure Index
The ankle brachial pressure index (API) is a clinical measurement of peripheral vascular perfusion.
Measured: 0 month
Ankle Brachial Pressure Index
The ankle brachial pressure index (API) is a clinical measurement of peripheral vascular perfusion.
Measured: 1 month
Ankle Brachial Pressure Index
The ankle brachial pressure index (API) is a clinical measurement of peripheral vascular perfusion.
Measured: 3 month
Ankle Brachial Pressure Index
The ankle brachial pressure index (API) is a clinical measurement of peripheral vascular perfusion.
Measured: 6 month
Ankle Brachial Pressure Index
The ankle brachial pressure index (API) is a clinical measurement of peripheral vascular perfusion.
Measured: 12 month
ELISA of angiogenic factors
10ml peripheral blood samples will be collected at multiple time points and human serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) will be analysed with an ELISA kit was processed according to its protocol.
Measured: 0 month
ELISA of angiogenic factors
10ml peripheral blood samples will be collected at multiple time points and human serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) will be analysed with an ELISA kit was processed according to its protocol.
Measured: 1 month
ELISA of angiogenic factors
10ml peripheral blood samples will be collected at multiple time points and human serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) will be analysed with an ELISA kit was processed according to its protocol.
Measured: 3 month
ELISA of angiogenic factors
10ml peripheral blood samples will be collected at multiple time points and human serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) will be analysed with an ELISA kit was processed according to its protocol.
Measured: 6 month
ELISA of angiogenic factors
10ml peripheral blood samples will be collected at multiple time points and human serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) will be analysed with an ELISA kit was processed according to its protocol.
Measured: 12 month
Immunostaining of angiogenic markers
3mm punch biopsy (RazorMed) will be obtained from the wound edge at multiple timepoints. The samples will be processed for paraffin embedding and 7μm serial thin sections will be cut. Markers for angiogenesis (CD31, alpha-SMA) and cell proliferation (Ki-67) antibodies will be used for immunostaining on the paraffin section according to the previously published protocol. The positively stained cell numbers in the DFU zone in each patient will be quantified using imaging software according to published protocol. The paired T test will be adopted to compare the difference of MSCs proportion, angiogenesis, and cell proliferation in each patient by SPSS 18.0 software for windows (SPSS, Chicago, IL, USA). Nonparametric test will be used for comparison of mean values with p<0.05 considered as statistically significant.
Measured: 0 month
Immunostaining of angiogenic markers
3mm punch biopsy (RazorMed) will be obtained from the wound edge at multiple timepoints. The samples will be processed for paraffin embedding and 7μm serial thin sections will be cut. Markers for angiogenesis (CD31, alpha-SMA) and cell proliferation (Ki-67) antibodies will be used for immunostaining on the paraffin section according to the previously published protocol. The positively stained cell numbers in the DFU zone in each patient will be quantified using imaging software according to published protocol. The paired T test will be adopted to compare the difference of MSCs proportion, angiogenesis, and cell proliferation in each patient by SPSS 18.0 software for windows (SPSS, Chicago, IL, USA). Nonparametric test will be used for comparison of mean values with p<0.05 considered as statistically significant.
Measured: 1 month
Immunostaining of angiogenic markers
3mm punch biopsy (RazorMed) will be obtained from the wound edge at multiple timepoints. The samples will be processed for paraffin embedding and 7μm serial thin sections will be cut. Markers for angiogenesis (CD31, alpha-SMA) and cell proliferation (Ki-67) antibodies will be used for immunostaining on the paraffin section according to the previously published protocol. The positively stained cell numbers in the DFU zone in each patient will be quantified using imaging software according to published protocol. The paired T test will be adopted to compare the difference of MSCs proportion, angiogenesis, and cell proliferation in each patient by SPSS 18.0 software for windows (SPSS, Chicago, IL, USA). Nonparametric test will be used for comparison of mean values with p<0.05 considered as statistically significant.
Measured: 3 month
Immunostaining of angiogenic markers
3mm punch biopsy (RazorMed) will be obtained from the wound edge at multiple timepoints. The samples will be processed for paraffin embedding and 7μm serial thin sections will be cut. Markers for angiogenesis (CD31, alpha-SMA) and cell proliferation (Ki-67) antibodies will be used for immunostaining on the paraffin section according to the previously published protocol. The positively stained cell numbers in the DFU zone in each patient will be quantified using imaging software according to published protocol. The paired T test will be adopted to compare the difference of MSCs proportion, angiogenesis, and cell proliferation in each patient by SPSS 18.0 software for windows (SPSS, Chicago, IL, USA). Nonparametric test will be used for comparison of mean values with p<0.05 considered as statistically significant.
Measured: 6 month
Immunostaining of angiogenic markers
3mm punch biopsy (RazorMed) will be obtained from the wound edge at multiple timepoints. The samples will be processed for paraffin embedding and 7μm serial thin sections will be cut. Markers for angiogenesis (CD31, alpha-SMA) and cell proliferation (Ki-67) antibodies will be used for immunostaining on the paraffin section according to the previously published protocol. The positively stained cell numbers in the DFU zone in each patient will be quantified using imaging software according to published protocol. The paired T test will be adopted to compare the difference of MSCs proportion, angiogenesis, and cell proliferation in each patient by SPSS 18.0 software for windows (SPSS, Chicago, IL, USA). Nonparametric test will be used for comparison of mean values with p<0.05 considered as statistically significant.
Measured: 12 month
Semmes Weinstein monofilament test
a monofilament sized 0.57, with a buckling force of 10gm, is the clinically accepted cutoff for the presence or absence of protective sensation. Measurements will be standardised to 3 sites; the 1st metatarsal, 3rd metatarsal and 5th metatarsal.
Measured: 0 month
Semmes Weinstein monofilament test
a monofilament sized 0.57, with a buckling force of 10gm, is the clinically accepted cutoff for the presence or absence of protective sensation. Measurements will be standardised to 3 sites; the 1st metatarsal, 3rd metatarsal and 5th metatarsal.
Measured: 1 month
Semmes Weinstein monofilament test
a monofilament sized 0.57, with a buckling force of 10gm, is the clinically accepted cutoff for the presence or absence of protective sensation. Measurements will be standardised to 3 sites; the 1st metatarsal, 3rd metatarsal and 5th metatarsal.
Measured: 3 month
Semmes Weinstein monofilament test
a monofilament sized 0.57, with a buckling force of 10gm, is the clinically accepted cutoff for the presence or absence of protective sensation. Measurements will be standardised to 3 sites; the 1st metatarsal, 3rd metatarsal and 5th metatarsal.
Measured: 6 month
Semmes Weinstein monofilament test
a monofilament sized 0.57, with a buckling force of 10gm, is the clinically accepted cutoff for the presence or absence of protective sensation. Measurements will be standardised to 3 sites; the 1st metatarsal, 3rd metatarsal and 5th metatarsal.
Measured: 12 month
Section of neurogenic markers
3mm punch biopsy (RazorMed) will be obtained from the wound edge at multiple timepoints. The samples will be processed for paraffin embedding and 7μm serial thin sections will be cut. The samples will be dewaxed and rehydrated. After antigen recovery (by Citrate Antigen Retrieval solution, ~30min, 65℃) and Permeabilization (by Triton™ X-100), markers for axon (beta-tubulin 3) (38) will be incubated overnight and corresponding secondary antibody will be incubated for 1 hours. The positively stained area in the DFU zone in each patient will be quantified using imaging software according to published protocol. The paired T test will be adopted to compare the difference of axon area in each patient by SPSS 18.0 software for windows (SPSS, Chicago, IL, USA). Nonparametric test will be used for comparison of mean values with p<0.05 considered as statistically significant.
Measured: 0 month
Section of neurogenic markers
3mm punch biopsy (RazorMed) will be obtained from the wound edge at multiple timepoints. The samples will be processed for paraffin embedding and 7μm serial thin sections will be cut. The samples will be dewaxed and rehydrated. After antigen recovery (by Citrate Antigen Retrieval solution, ~30min, 65℃) and Permeabilization (by Triton™ X-100), markers for axon (beta-tubulin 3) (38) will be incubated overnight and corresponding secondary antibody will be incubated for 1 hours. The positively stained area in the DFU zone in each patient will be quantified using imaging software according to published protocol. The paired T test will be adopted to compare the difference of axon area in each patient by SPSS 18.0 software for windows (SPSS, Chicago, IL, USA). Nonparametric test will be used for comparison of mean values with p<0.05 considered as statistically significant.
Measured: 1 month
Section of neurogenic markers
3mm punch biopsy (RazorMed) will be obtained from the wound edge at multiple timepoints. The samples will be processed for paraffin embedding and 7μm serial thin sections will be cut. The samples will be dewaxed and rehydrated. After antigen recovery (by Citrate Antigen Retrieval solution, ~30min, 65℃) and Permeabilization (by Triton™ X-100), markers for axon (beta-tubulin 3) (38) will be incubated overnight and corresponding secondary antibody will be incubated for 1 hours. The positively stained area in the DFU zone in each patient will be quantified using imaging software according to published protocol. The paired T test will be adopted to compare the difference of axon area in each patient by SPSS 18.0 software for windows (SPSS, Chicago, IL, USA). Nonparametric test will be used for comparison of mean values with p<0.05 considered as statistically significant.
Measured: 3 month
Section of neurogenic markers
3mm punch biopsy (RazorMed) will be obtained from the wound edge at multiple timepoints. The samples will be processed for paraffin embedding and 7μm serial thin sections will be cut. The samples will be dewaxed and rehydrated. After antigen recovery (by Citrate Antigen Retrieval solution, ~30min, 65℃) and Permeabilization (by Triton™ X-100), markers for axon (beta-tubulin 3) (38) will be incubated overnight and corresponding secondary antibody will be incubated for 1 hours. The positively stained area in the DFU zone in each patient will be quantified using imaging software according to published protocol. The paired T test will be adopted to compare the difference of axon area in each patient by SPSS 18.0 software for windows (SPSS, Chicago, IL, USA). Nonparametric test will be used for comparison of mean values with p<0.05 considered as statistically significant.
Measured: 6 month
Section of neurogenic markers
3mm punch biopsy (RazorMed) will be obtained from the wound edge at multiple timepoints. The samples will be processed for paraffin embedding and 7μm serial thin sections will be cut. The samples will be dewaxed and rehydrated. After antigen recovery (by Citrate Antigen Retrieval solution, ~30min, 65℃) and Permeabilization (by Triton™ X-100), markers for axon (beta-tubulin 3) (38) will be incubated overnight and corresponding secondary antibody will be incubated for 1 hours. The positively stained area in the DFU zone in each patient will be quantified using imaging software according to published protocol. The paired T test will be adopted to compare the difference of axon area in each patient by SPSS 18.0 software for windows (SPSS, Chicago, IL, USA). Nonparametric test will be used for comparison of mean values with p<0.05 considered as statistically significant.
Measured: 12 month
Inflammatory cell flow cytometry
10ml of peripheral blood will be obtained. Mononuclear cells will be collected by isolation of Ficoll-Paque density gradient centrifugation. The populations of classical and non-classical monocytes will be analyzed by flow cytometry and identified from proportions of CD172a+ and CD43+ cells.
Measured: 0 month
Inflammatory cell flow cytometry
10ml of peripheral blood will be obtained. Mononuclear cells will be collected by isolation of Ficoll-Paque density gradient centrifugation. The populations of classical and non-classical monocytes will be analyzed by flow cytometry and identified from proportions of CD172a+ and CD43+ cells.
Measured: 1 month
Inflammatory cell flow cytometry
10ml of peripheral blood will be obtained. Mononuclear cells will be collected by isolation of Ficoll-Paque density gradient centrifugation. The populations of classical and non-classical monocytes will be analyzed by flow cytometry and identified from proportions of CD172a+ and CD43+ cells.
Measured: 3 month
Inflammatory cell flow cytometry
10ml of peripheral blood will be obtained. Mononuclear cells will be collected by isolation of Ficoll-Paque density gradient centrifugation. The populations of classical and non-classical monocytes will be analyzed by flow cytometry and identified from proportions of CD172a+ and CD43+ cells.
Measured: 6 month
Inflammatory cell flow cytometry
10ml of peripheral blood will be obtained. Mononuclear cells will be collected by isolation of Ficoll-Paque density gradient centrifugation. The populations of classical and non-classical monocytes will be analyzed by flow cytometry and identified from proportions of CD172a+ and CD43+ cells.
Measured: 12 month
Macrophage Immunofluorescence staining
A 3mm punch biopsy (RazorMed) will be obtained and prepared for paraffin sections. The populations and localisations of both monocytes (classical and non-classical phenotypes) and macrophages (M1 and M2 phenotype) in the skin wound site will be determined by immunofluorescence staining with specific antibodies to CD68 (general marker for macrophage), anti-iNOS (M1 macrophage), CD206 (M2 macrophage) [32] CD172a (general marker for monocyte) and CD43 (non-classical monocyte specific marker).
Measured: 0 month
Macrophage Immunofluorescence staining
A 3mm punch biopsy (RazorMed) will be obtained and prepared for paraffin sections. The populations and localisations of both monocytes (classical and non-classical phenotypes) and macrophages (M1 and M2 phenotype) in the skin wound site will be determined by immunofluorescence staining with specific antibodies to CD68 (general marker for macrophage), anti-iNOS (M1 macrophage), CD206 (M2 macrophage) [32] CD172a (general marker for monocyte) and CD43 (non-classical monocyte specific marker).
Measured: 1 month
Macrophage Immunofluorescence staining
A 3mm punch biopsy (RazorMed) will be obtained and prepared for paraffin sections. The populations and localisations of both monocytes (classical and non-classical phenotypes) and macrophages (M1 and M2 phenotype) in the skin wound site will be determined by immunofluorescence staining with specific antibodies to CD68 (general marker for macrophage), anti-iNOS (M1 macrophage), CD206 (M2 macrophage) [32] CD172a (general marker for monocyte) and CD43 (non-classical monocyte specific marker).
Measured: 3 month
Macrophage Immunofluorescence staining
A 3mm punch biopsy (RazorMed) will be obtained and prepared for paraffin sections. The populations and localisations of both monocytes (classical and non-classical phenotypes) and macrophages (M1 and M2 phenotype) in the skin wound site will be determined by immunofluorescence staining with specific antibodies to CD68 (general marker for macrophage), anti-iNOS (M1 macrophage), CD206 (M2 macrophage) [32] CD172a (general marker for monocyte) and CD43 (non-classical monocyte specific marker).
Measured: 6 month
Macrophage Immunofluorescence staining
A 3mm punch biopsy (RazorMed) will be obtained and prepared for paraffin sections. The populations and localisations of both monocytes (classical and non-classical phenotypes) and macrophages (M1 and M2 phenotype) in the skin wound site will be determined by immunofluorescence staining with specific antibodies to CD68 (general marker for macrophage), anti-iNOS (M1 macrophage), CD206 (M2 macrophage) [32] CD172a (general marker for monocyte) and CD43 (non-classical monocyte specific marker).
Measured: 12 month
Identification of regulatory cytokines for peripheral blood mesenchymal stem cells (PB-MSCs) mobilization
10ml of peripheral blood will be collected at multiple timepoints. Each peripheral blood samples will be collected using tubes containing K2-EDTA. Blood samples will be centrifuged at 1800g for 6 min at 4 °C to get plasma and apportioned into 1 mL aliquots and stored at -80 °C. Differential protein expression will be determined by 8-plex isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics analysis.
Measured: 0 month
Identification of regulatory cytokines for peripheral blood mesenchymal stem cells (PB-MSCs) mobilization
10ml of peripheral blood will be collected at multiple timepoints. Each peripheral blood samples will be collected using tubes containing K2-EDTA. Blood samples will be centrifuged at 1800g for 6 min at 4 °C to get plasma and apportioned into 1 mL aliquots and stored at -80 °C. Differential protein expression will be determined by 8-plex isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics analysis.
Measured: 1 month
Identification of regulatory cytokines for peripheral blood mesenchymal stem cells (PB-MSCs) mobilization
10ml of peripheral blood will be collected at multiple timepoints. Each peripheral blood samples will be collected using tubes containing K2-EDTA. Blood samples will be centrifuged at 1800g for 6 min at 4 °C to get plasma and apportioned into 1 mL aliquots and stored at -80 °C. Differential protein expression will be determined by 8-plex isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics analysis.
Measured: 3 month
Identification of regulatory cytokines for peripheral blood mesenchymal stem cells (PB-MSCs) mobilization
10ml of peripheral blood will be collected at multiple timepoints. Each peripheral blood samples will be collected using tubes containing K2-EDTA. Blood samples will be centrifuged at 1800g for 6 min at 4 °C to get plasma and apportioned into 1 mL aliquots and stored at -80 °C. Differential protein expression will be determined by 8-plex isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics analysis.
Measured: 6 month
Identification of regulatory cytokines for peripheral blood mesenchymal stem cells (PB-MSCs) mobilization
10ml of peripheral blood will be collected at multiple timepoints. Each peripheral blood samples will be collected using tubes containing K2-EDTA. Blood samples will be centrifuged at 1800g for 6 min at 4 °C to get plasma and apportioned into 1 mL aliquots and stored at -80 °C. Differential protein expression will be determined by 8-plex isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics analysis.
Measured: 12 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2023
- Study start1 Dec 2023 (estimated)
- Primary completion31 Jan 2026 (estimated)
- Study completion31 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Foot UlcerStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Samuel KK Ling, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05704075
- Sponsor's protocol ID
- TTTFootUlcers
- Status last verified
- Jan 2023
- First submitted
- 13 Oct 2022
- Last updated
- 30 Jan 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical and Mechanistic Study of Transverse Tibial Transport in Complex Foot Ulcers
- ClinicalTrials.gov ID
- NCT05704075
- Acronym / sponsor ID
- TTTFootUlcers
- Conditions
- Diabetic Foot Ulcer
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- 1 Dec 2023 (estimated)
- Primary completion
- 31 Jan 2026 (estimated)
- Study completion
- 31 Jan 2026 (estimated)
- First posted
- 30 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
TTT is a novel surgical technique that may potentially solve the long-standing deficit of seeking effective treatment for diabetic foot ulcers, decreasing the need for amputations and softening the socio-economic impact it brings. This trial will be the world's first prospective RCT to verify the promising clinical studies on the clinical benefit of TTT in treating diabetic foot ulcers. In addition, blood samples from this study will allow us to study the various systemic circulating soluble factors in relation to neovascularisation, immunomodulation, and stem cell mobilisation. By taking the blood and various time points, we will better understand the complex interplay between various biomarkers. This GRF will allow us to obtain tissue samples to analyse the histological cellular changes after TTT surgery. It will provide us with more insight on how TTT works, as well as potentially helping us pinpoint the important changes and timeframes related to this intervention.
The PI, Co-Is and collaborators create a strong team of clinicians and scientists with a solid clinical and basic science track record. The team has published guidelines and surgical techniques in TTT and run several training cadaveric workshops teaching the TTT surgical technique to local orthopaedic surgeons. The team has also established a rat TTT model and published on TTT immunomodulation and neovascularisation in addition to other ongoing mechanistic experiments in animals.
This prospective multi-centre randomised controlled trial may act as the foundation for launching this cost-effective TTT surgery to regulate neovascularisation, neurogenesis, immunomodulation and mobilisation of MSCs for the treatment of various chronic conditions. Regenerative medicine is a multi-million dollar industry, and the potential use of TTT can result in a range of clinical applications not limited to DFUs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Group | Other | Procedure: ConventionalConventional Treatment: Dressing + Negative Pressure Wound Therapy |
| TTT Group | Experimental | Procedure: Transverse Tibial Transport (TTT)Dressing + Negative Pressure Wound Therapy + Transverse Tibial Transport |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adults >18 years old
- Patients with a Wagner stage 4 Foot ulcer (partial foot gangrene)
- No active wound infection as confirmed by bacterial fluorescence imaging. (the Moleculight i:X, Smith and Nephew handheld device illuminates with 405nm violet light which causes bacteria to emit characteristic endogenous fluorescence signals that are visualised in real-time on the device's screen, allowing an objective measure of adequate surgical debridement)
- Biochemically confirmed diabetes with fasting plasma glucose ≥ 7.0 mmol/L, or a random plasma glucose ≥ 11.1 mmol/L or haemoglobin A1c (HbA1c) level ≥ 6.5%
- Triaged out for angioplasty/vascular bypass by the vascular surgeon
Key exclusion criteria (6 listed)
- Uncontrolled sepsis
- Contraindications for applying an external fixator device in the tibia (overlying skin conditions, surgical hardware such as tibial nails, total knee prosthesis etc.)
- Severe medical comorbidities precluding safe anaesthesia (recent myocardial infarct, limited pulmonary function etc.)
- Mental or physical disability which may impair the ability to adhere to the intervention plan, e.g. severe dementia, psychosis etc.
- Recent revascularisation procedure (<12 weeks)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transverse Tibial Transport (TTT)Transverse tibial transport is a novel adaptation of concepts used in distraction histogenesis. The most common use of this surgical principle is in bone lengthening surgery, which is a well-established surgical procedure by applying an external fixator to the bone, creating a corticotomy, and gradually lengthening the bone at the optimal rate of 0.5mm/12hrs. The biological mechanisms of distraction histogenesis involve activating signalling pathways such as cytokines Interleukin 1 and Interleukin 6, pro-inflammatory markers TNF alpha, pro-osteogenic TGF-beta, BMPs and pro-angiogenic factors VEGF and angiopoietin . TTT utilises the concept of distraction histiogenesis, but distraction is performed in the transverse plane instead of a longitudinal distraction. In addition, the period of distraction is coupled with a corresponding compression period and ultimately results in no net change in limb length. | Procedure or surgery | TTT Group |
| ConventionalDressing + Negative Pressure Wound Therapy | Procedure or surgery | Control Group |
Primary outcome
Wound Size
Time frame: 0 month
Wound size will be measured using digital photography with standardised marker dots.
Wound Size
Time frame: 1 month
Wound size will be measured using digital photography with standardised marker dots.
Wound Size
Time frame: 3 month
Wound size will be measured using digital photography with standardised marker dots.
Wound Size
Time frame: 6 month
Wound size will be measured using digital photography with standardised marker dots.
Wound Size
Time frame: 12 month
Wound size will be measured using digital photography with standardised marker dots.
46 secondary outcomes
Foot Function
Time frame: 0 month
Foot Function
Time frame: 1 month
Foot Function
Time frame: 3 month
Foot Function
Time frame: 6 month
Foot Function
Time frame: 12 month
Incidence of Amputation
Time frame: Up to 52 weeks
Ankle Brachial Pressure Index
Time frame: 0 month
Ankle Brachial Pressure Index
Time frame: 1 month
Ankle Brachial Pressure Index
Time frame: 3 month
Ankle Brachial Pressure Index
Time frame: 6 month
Ankle Brachial Pressure Index
Time frame: 12 month
ELISA of angiogenic factors
Time frame: 0 month
ELISA of angiogenic factors
Time frame: 1 month
ELISA of angiogenic factors
Time frame: 3 month
ELISA of angiogenic factors
Time frame: 6 month
ELISA of angiogenic factors
Time frame: 12 month
Immunostaining of angiogenic markers
Time frame: 0 month
Immunostaining of angiogenic markers
Time frame: 1 month
Immunostaining of angiogenic markers
Time frame: 3 month
Immunostaining of angiogenic markers
Time frame: 6 month
Immunostaining of angiogenic markers
Time frame: 12 month
Semmes Weinstein monofilament test
Time frame: 0 month
Semmes Weinstein monofilament test
Time frame: 1 month
Semmes Weinstein monofilament test
Time frame: 3 month
Semmes Weinstein monofilament test
Time frame: 6 month
Semmes Weinstein monofilament test
Time frame: 12 month
Section of neurogenic markers
Time frame: 0 month
Section of neurogenic markers
Time frame: 1 month
Section of neurogenic markers
Time frame: 3 month
Section of neurogenic markers
Time frame: 6 month
Section of neurogenic markers
Time frame: 12 month
Inflammatory cell flow cytometry
Time frame: 0 month
Inflammatory cell flow cytometry
Time frame: 1 month
Inflammatory cell flow cytometry
Time frame: 3 month
Inflammatory cell flow cytometry
Time frame: 6 month
Inflammatory cell flow cytometry
Time frame: 12 month
Macrophage Immunofluorescence staining
Time frame: 0 month
Macrophage Immunofluorescence staining
Time frame: 1 month
Macrophage Immunofluorescence staining
Time frame: 3 month
Macrophage Immunofluorescence staining
Time frame: 6 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2023.
Related trials for Diabetic Foot Ulcer
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
Active, not recruiting
Wearable Insoles for Recurrent Diabetic Ulcer Prevention
Diabetes, Peripheral Neuropathy
Active, not recruiting
Evaluation of Personalized Nutritional Intervention on Wound Healing of Cutaneous Ulcers in Diabetics
Foot, Diabetic
Not yet recruiting
Efficacy Evaluation of Turmeric-Derived Nanoparticle Hydrogel for the Treatment of Diabetic Foot Ulcer Wounds
Diabete Mellitus
Not yet recruiting
Better Care Closer to Home: Enhancing Primary and Community Care
Diabetic Foot Disease, Recurrence
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Transverse Tibial Transport (TTT) and Conventional in people with Diabetic Foot Ulcer, run by Chinese University of Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Wound Size (time frame: 0 month). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2023.