Transverse Tibial Bone Transport (TTT) in the Management of Chronic Diabetic Lower Extremity Wounds

Official title

SMILE - TTT: Surgical MIcrovascularization of Lower Extremities for Diabetic Foot Ulcers - Transverse Tibial Transport Study

Overview

The purpose of this study is to evaluate the safety and clinical performance of transverse tibial bone transport in patients with chronic ischemic and diabetic lower extremity ulcers. This study will assess wound healing outcomes and limb preservation in a population with limited therapeutic alternatives.

Detailed description

Diabetic lower extremity ulcers are associated with impaired blood flow, delayed wound healing, high morbidity, and an increased risk of limb loss. In some patients, conventional treatments such as wound care, revascularization procedures, or adjunctive therapies are ineffective or not feasible, leaving limited options short of major amputation.

Transverse tibial bone transport (TTT) is a surgical technique that applies controlled distraction to the tibial cortex and has been reported in prior clinical studies to stimulate angiogenesis, improve local perfusion, and support wound healing in ischemic conditions.

Interventions

• Device Biodynamik XT3
  Application of XT3 system and transverse tibial bone transport procedure

Primary outcome measures

• Proportion of subjects with wound closure [Time frame: From enrollment to 18 weeks]

Secondary outcome measures (11)

• Mean PAR summarized at 8 and 18 weeks [Time frame: From enrollment to 18 weeks]
• Proportion of patients with greater than 60% PAR [Time frame: From enrollment until 18 weeks]
• Frequency of subsequent procedures [Time frame: From enrollment to 18 weeks]
• Vascular changes as measured by Ankle Brachial Index (ABI) [Time frame: From enrollment to 18 weeks, 6, 9 and 12 months]
• Improvement in Visual Analog Scale to measure pain [Time frame: From enrollment to 18 weeks]
• Frequency of wound recurrence [Time frame: Enrollment until 12 months]
• Amputation free survival [Time frame: Enrollment until 12 months]
• Vascular changes as measured by Transcutaneous Oxygen Pressure (TcPO2) [Time frame: Measured at baseline to 18 weeks and through 12 months]
• Improvement in Patient Reported Outcome Wound-QoL-17 at 16 weeks [Time frame: From enrollment to 18 weeks]
• Time to achieve wound closure [Time frame: Enrollment through 18 weeks and 12 months]
• Time to heal for surgical site [Time frame: Enrollment to 18 weeks]

Eligibility criteria

Inclusion criteria

• Adults (>=22 years).
• Chronic diabetic foot ulcer wound persisting >=12 weeks and less than 104 weeks refractory to standard wound care.
• Wound location within distal 1/3 tibia and below including foot.
• Wound stages: WiFi >= 3
• At least one patent lower extremity tibial vessel (after revascularization if needed).
• Able to provide informed consent and comply with study procedures.

Exclusion criteria

• Active systemic infection (positive blood cultures)
• Severe sepsis (2 out of 4 SIRS criteria with impact on organ dysfunction)
• Subacute lower extremity wound <12 weeks with or without standard wound cares
• Internal hardware within 10cm of possible TTT placement
• Most proximal aspect of wound within 10cm of most distal pin of possible TTT placement
• End Stage Renal Disease requiring dialysis
• Renal function values

• eGFR: <15ml/min and
• Creatinine: >6mg/dL and
• BUN: >50 mg/dL
• Wounds less than 1 cm3 or greater than 30 cm3
• Corticosteroids >10mg prednisone equivalent daily for >2 weeks
• Patients with osteomyelitis in the ipsilateral tibia at planned corticotomy site
• Cognitive or social limitations precluding consent or follow-up
• Current participation in another investigational study (drug or device)
• Immunocompromised (WBC <4) or undergoing active chemotherapy
• Hemoglobin A1c >12
• BMI <18.5 kg/m2
• Pregnant, lactating, or planning to become pregnant
• Life expectancy less than 12 months
• Severe hepatic impairment defined by patient on a transplant list, MELD > 20, Child's class C.
• A history of conditions that may impair wound healing in the opinion of the Investigator, for example, autoimmune disorders, renal failure patients on dialysis, or medications that impair the healing process.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Mayo Clinic — Jacksonville

Publications

• Nie X, Kuang X, Liu G, Zhong Z, Ding Y, Yu J, Liu J, Li S, He L, Su H, Qin W, Zhao J, Hua Q, Chen Y. Tibial cortex transverse transport facilitating healing in patients with recalcitrant non-diabetic leg ulcers. J Orthop Translat. 2020 Dec 9;27:1-7. doi: 10.1016/j.jot.2020.11.001. eCollection 2021 Mar. PMID 33344165
• Chen Y, Kuang X, Zhou J, Zhen P, Zeng Z, Lin Z, Gao W, He L, Ding Y, Liu G, Qiu S, Qin A, Lu W, Lao S, Zhao J, Hua Q. Proximal Tibial Cortex Transverse Distraction Facilitating Healing and Limb Salvage in Severe and Recalcitrant Diabetic Foot Ulcers. Clin Orthop Relat Res. 2020 Apr;478(4):836-851. doi: 10.1097/CORR.0000000000001075. PMID 31794478
• Luxon A, Syziu A, Harrison WD, Islam A, Mason L. A Systematic Review on Tibial Cortex Transverse Transport in the Treatment of Ischemic Ulcers of the Lower Limb. Foot Ankle Int. 2025 Aug;46(8):914-924. doi: 10.1177/10711007251341312. Epub 2025 Jun 26. PMID 40567177
• Chen Y, Ding X, Zhu Y, Jia Z, Qi Y, Chen M, Lu J, Kuang X, Zhou J, Su Y, Zhao Y, Lu W, Zhao J, Hua Q. Effect of tibial cortex transverse transport in patients with recalcitrant diabetic foot ulcers: A prospective multicenter cohort study. J Orthop Translat. 2022 Oct 12;36:194-204. doi: 10.1016/j.jot.2022.09.002. eCollection 2022 Sep. PMID 36263383
• Ding Y, Yu D, Huang H, Peng X, Yang S, Lin Z, Zhou P, Liang J, Zou X, Mo R, Pan K, Zheng P, Kuang X, Nie X, Hua Q. Combining Tibial Cortex Transverse Transport (TTT) and Endovascular Therapy (EVT) for Limb Salvage in Chronic Limb-Threatening Ischemia. Orthop Surg. 2024 Sep;16(9):2132-2139. doi: 10.1111/os.14222. Epub 2024 Sep 7. PMID 39243174
• Liao MM, Zhang F, Wang YK, Wang MW, Cao JR, Jin ZH, Ren YJ, Chen S. Transverse tibial bone transport promotes distraction osteogenesis and improves blood flow in the management of diabetic foot. World J Diabetes. 2026 Jan 15;17(1):111847. doi: 10.4239/wjd.v17.i1.111847. PMID 41608106
• Ou S, Xu C, Yang Y, Chen Y, Li W, Lu H, Li G, Sun H, Qi Y. Transverse Tibial Bone Transport Enhances Distraction Osteogenesis and Vascularization in the Treatment of Diabetic Foot. Orthop Surg. 2022 Sep;14(9):2170-2179. doi: 10.1111/os.13416. Epub 2022 Aug 10. PMID 35946439
• Hu XX, Xiu ZZ, Li GC, Zhang JY, Shu LJ, Chen Z, Li H, Zou QF, Zhou Q. Effectiveness of transverse tibial bone transport in treatment of diabetic foot ulcer: A systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023 Jan 4;13:1095361. doi: 10.3389/fendo.2022.1095361. eCollection 2022. PMID 36686461

Identifiers

NCT: NCT07444593 · BD-TTT-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗