Clinical trial NCT05704075: Clinical and Mechanistic Study of Transverse Tibial Transport in Complex Foot Ulcers
Official title: Clinical and Mechanistic Study of Transverse Tibial Transport in Complex Foot Ulcers
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Diabetic Foot Ulcer
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2023-01-30
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.)

Primary outcomes:
measure: Wound Size
timeFrame: 0 month
measure: Wound Size
timeFrame: 1 month
measure: Wound Size
timeFrame: 3 month
measure: Wound Size
timeFrame: 6 month
measure: Wound Size
timeFrame: 12 month
Secondary outcomes:
measure: Foot Function
timeFrame: 0 month
measure: Foot Function
timeFrame: 1 month
measure: Foot Function
timeFrame: 3 month
measure: Foot Function
timeFrame: 6 month
measure: Foot Function
timeFrame: 12 month
measure: Incidence of Amputation
timeFrame: Up to 52 weeks
measure: Ankle Brachial Pressure Index
timeFrame: 0 month
measure: Ankle Brachial Pressure Index
timeFrame: 1 month
measure: Ankle Brachial Pressure Index
timeFrame: 3 month
measure: Ankle Brachial Pressure Index
timeFrame: 6 month
measure: Ankle Brachial Pressure Index
timeFrame: 12 month
measure: ELISA of angiogenic factors
timeFrame: 0 month
measure: ELISA of angiogenic factors
timeFrame: 1 month
measure: ELISA of angiogenic factors
timeFrame: 3 month
measure: ELISA of angiogenic factors
timeFrame: 6 month
measure: ELISA of angiogenic factors
timeFrame: 12 month
measure: Immunostaining of angiogenic markers
timeFrame: 0 month
measure: Immunostaining of angiogenic markers
timeFrame: 1 month
measure: Immunostaining of angiogenic markers
timeFrame: 3 month
measure: Immunostaining of angiogenic markers
timeFrame: 6 month
measure: Immunostaining of angiogenic markers
timeFrame: 12 month
measure: Semmes Weinstein monofilament test
timeFrame: 0 month
measure: Semmes Weinstein monofilament test
timeFrame: 1 month
measure: Semmes Weinstein monofilament test
timeFrame: 3 month
measure: Semmes Weinstein monofilament test
timeFrame: 6 month
measure: Semmes Weinstein monofilament test
timeFrame: 12 month
measure: Section of neurogenic markers
timeFrame: 0 month
measure: Section of neurogenic markers
timeFrame: 1 month
measure: Section of neurogenic markers
timeFrame: 3 month
measure: Section of neurogenic markers
timeFrame: 6 month
measure: Section of neurogenic markers
timeFrame: 12 month
measure: Inflammatory cell flow cytometry
timeFrame: 0 month
measure: Inflammatory cell flow cytometry
timeFrame: 1 month
measure: Inflammatory cell flow cytometry
timeFrame: 3 month
measure: Inflammatory cell flow cytometry
timeFrame: 6 month
measure: Inflammatory cell flow cytometry
timeFrame: 12 month
measure: Macrophage Immunofluorescence staining
timeFrame: 0 month
measure: Macrophage Immunofluorescence staining
timeFrame: 1 month
measure: Macrophage Immunofluorescence staining
timeFrame: 3 month
measure: Macrophage Immunofluorescence staining
timeFrame: 6 month
measure: Macrophage Immunofluorescence staining
timeFrame: 12 month
measure: Identification of regulatory cytokines for peripheral blood mesenchymal stem cells (PB-MSCs) mobilization
timeFrame: 0 month
measure: Identification of regulatory cytokines for peripheral blood mesenchymal stem cells (PB-MSCs) mobilization
timeFrame: 1 month
measure: Identification of regulatory cytokines for peripheral blood mesenchymal stem cells (PB-MSCs) mobilization
timeFrame: 3 month
measure: Identification of regulatory cytokines for peripheral blood mesenchymal stem cells (PB-MSCs) mobilization
timeFrame: 6 month
measure: Identification of regulatory cytokines for peripheral blood mesenchymal stem cells (PB-MSCs) mobilization
timeFrame: 12 month
Other outcomes:
Locations:
Study officials:
References: