Clinical and Mechanistic Study of Transverse Tibial Transport in Complex Foot Ulcers

NCT ID: NCT05704075

Last Updated: 2023-01-30

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-01
• Study Completion Date: 2026-01-31

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.

Conditions

Diabetic Foot Ulcer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control Group

Conventional Treatment: Dressing + Negative Pressure Wound Therapy

Group Type: OTHER

Conventional

Intervention Type: PROCEDURE

Dressing + Negative Pressure Wound Therapy

TTT Group

Dressing + Negative Pressure Wound Therapy + Transverse Tibial Transport

Group Type: EXPERIMENTAL

Transverse Tibial Transport (TTT)

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: PROCEDURE

Conventional

Dressing + Negative Pressure Wound Therapy

Intervention Type: PROCEDURE

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.)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Samuel KK Ling

Clinical Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

TTTFootUlcers

Identifier Type: -

Identifier Source: org_study_id