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

NCT05704075 | Unknown

• 1 other identifier: TTTFootUlcers
• Study Type: interventional
• Target: 54
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (5)

• Wound Size

  Wound size will be measured using digital photography with standardised marker dots.

  0 month

• Wound Size

  Wound size will be measured using digital photography with standardised marker dots.

  1 month

• Wound Size

  Wound size will be measured using digital photography with standardised marker dots.

  3 month

• Wound Size

  Wound size will be measured using digital photography with standardised marker dots.

  6 month

• Wound Size

  Wound size will be measured using digital photography with standardised marker dots.

  12 month

Secondary Outcomes (46)

• Foot Function

  0 month

• Foot Function

  1 month

• Foot Function

  3 month

• Foot Function

  6 month

• Foot Function

  12 month

Study Arms (2)

Control Group

OTHER

Conventional Treatment: Dressing + Negative Pressure Wound Therapy

Procedure: Conventional

TTT Group

EXPERIMENTAL

Dressing + Negative Pressure Wound Therapy + Transverse Tibial Transport

Procedure: Transverse Tibial Transport (TTT)

Interventions

Transverse Tibial Transport (TTT) 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.

TTT Group

Conventional PROCEDURE

Dressing + Negative Pressure Wound Therapy

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.)

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

MeSH Terms

Conditions

Diabetic Foot

Interventions

Congresses as Topic

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Intervention Hierarchy (Ancestors)

Organizations; Health Care Economics and Organizations

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: October 13, 2022
• First Posted: January 30, 2023
• Study Start: December 1, 2023
• Primary Completion: January 31, 2026
• Study Completion: January 31, 2026
• Last Updated: January 30, 2023

Record last verified: 2023-01