Longitudinal Evaluation of Direct Neurotization Technique in Breast Reconstruction With Fully Autologous Components

Официальное название

Longitudinal Evaluation of Direct Neurotization Technique in Breast Reconstruction With Fully Autologous Components: An Assessment of BREAST-Q Sensation Module, Cutaneous Pressure Threshold, Neuregulin 1 (NRG1) Expression, Nerve Fiber Cross-sectional Area, Intraepidermal Nerve Fiber Density (IENFD), and Breast Morphometry

Обзор

This clinical trial aims to evaluate whether direct neurotization using fully autologous components during autologous breast reconstruction improves postoperative breast sensation and sensory-related quality of life in women undergoing unilateral mastectomy. Direct neurotization involves coapting the recipient intercostal nerve to an autologous nerve graft placed within the flap to facilitate reinnervation. The study's primary questions are: 1. Does direct neurotization using fully autologous nerve grafts improve cutaneous sensory recovery, as assessed by Semmes-Weinstein monofilament thresholds measured at standardized breast locations? 2. Does neurotization enhance patient-reported sensory outcomes and quality of life, as assessed by the BREAST-Q Sensation Module? As secondary objectives, the study will assess whether biological predictors of nerve regeneration correlate with sensory outcomes. These include: 1. Neuregulin-1 (NRG1) expression in flap tissue biopsy; 2. Cross-sectional area of the recipient nerve fibres; 3. Breast morphometry measured at baseline and follow-up; 4. Intraepidermal nerve fibre density (IENFD) on skin biopsy. Participants will be randomly assigned to receive either: 1. Neurotized autologous breast reconstruction using fully autologous graft components, or 2. Standard (non-neurotized) autologous breast reconstruction. The study will compare these groups to determine whether neurotization accelerates or enhances the return of breast sensation over a 6-month follow-up period, with evaluations at 1 month, 3 months, and 6 months after surgery. Participants will undergo: 1. Autologous breast reconstruction with or without direct neurotization as part of their planned cancer surgery. 2. Sensory testing using Semmes-Weinstein monofilaments at baseline, 1, 3, and 6 months. 3. Completion of BREAST-Q questionnaires evaluating breast sensation, symptoms, and quality of life at each follow-up visit. 3\. Intraoperative tissue sampling for NRG1 analysis and nerve morphometry. 4. Skin biopsy (if applicable) to assess intraepidermal nerve fibre density. 5. Breast morphometry assessment using a breast morphometry measurement software tool. This study seeks to provide high-quality evidence on the effectiveness of direct neurotization using fully autologous components in restoring breast sensation and to explore biological predictors that may influence sensory recovery after autologous breast reconstruction.

Вмешательства

• Процедура Autologous Breast Reconstruction With Direct Neurotization
  The direct neurotization using fully autologous components procedures include: 1. Direct neurotization is carried out using fully autologous components, involving coaptation of the recipient nerve to an autologous nerve graft placed within the flap to facilitate reinnervation. 2. Surgical breast reconstruction is then completed using patient's own tissue
• Процедура Autologous Breast Reconstruction without Neurotization
  Breast reconstruction is performed using autologous tissue without nerve coaptation or neurotization, according to standard surgical practice.

Первичные конечные точки

• Breast Sensation assessed by using Semmes-Weinstein Monofilament testing [Срок оценки: 1, 3 and 6 months after Neurotization]
• Patient's Quality of Life assessed by using BREAST-Q® Sensation Module [Срок оценки: 1, 3 and 6 months after Neurotization]

Вторичные конечные точки (4)

• Neuregulin 1 Expression [Срок оценки: During procedure and 6 months after surgery]
• Nerve Cross-sectional Area [Срок оценки: Measured during neurotization procedure]
• Breast Morphometry [Срок оценки: Before surgery and 1, 3, 6 months after surgery]
• Intraepidermal Nerve Fibre Density (IENFD) [Срок оценки: During procedure and 6 months after surgery]

Критерии участия

Критерии включения

• Female patients aged ≥18 years.
• Patients with unilateral breast cancer who have undergone or will undergo unilateral mastectomy.
• Patients undergoing breast reconstruction.
• Patients with unilateral breast cancer regardless of adjuvant therapy status (receiving radiotherapy and/or chemotherapy or receiving no adjuvant therapy).
• Willing to comply with all scheduled examinations and tissue sampling procedures.
• Able and willing to provide written informed consent.

Критерии исключения

• History of peripheral neuropathy (e.g., diabetes mellitus with neuropathic complications).
• Bilateral mastectomy.
• Presence of skin or soft-tissue conditions of the breast that may interfere with sensory assessment.
• Active smokers (use of tobacco, vape, or other nicotine products within 14 days prior to neurotization).
• Refusal or inability to attend follow-up evaluations.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Индонезия · 1 центр

• dr. Ciptomangunkusumo National Hospital - Faculty of Medicine Universitas Indonesia — Jakarta Pusat

Публикации

• Bubberman JM, Brandts L, van Kuijk SMJ, van der Hulst RRWJ, Tuinder SMH. The efficacy of sensory nerve coaptation in DIEP flap breast reconstruction - Preliminary results of a double-blind randomized controlled trial. Breast. 2024 Apr;74:103691. doi: 10.1016/j.breast.2024.103691. Epub 2024 Feb 9. PMID 38401421
• Timar B, Popescu S, Timar R, Baderca F, Duica B, Vlad M, Levai C, Balinisteanu B, Simu M. The usefulness of quantifying intraepidermal nerve fibers density in the diagnostic of diabetic peripheral neuropathy: a cross-sectional study. Diabetol Metab Syndr. 2016 Apr 11;8:31. doi: 10.1186/s13098-016-0146-4. eCollection 2016. PMID 27069510
• Samolis A, Troupis T, Politis C, Pantazis N, Triantafyllou G, Tsakotos G, Tegos T, Lazaridis N, Natsis K, Piagkou M. Intraepidermal Nerve Fiber Density as an Indicator of Neuropathy Predisposition: A Systematic Review with Meta-Analysis. Diagnostics (Basel). 2025 May 23;15(11):1311. doi: 10.3390/diagnostics15111311. PMID 40506883
• La Padula S, Pensato R, D'Andrea F, de Gregorio L, Errico C, Rega U, Canta L, Pizza C, Roccaro G, Billon R, Dibra E, Meningaud JP, Hersant B. Assessment of Patient Satisfaction Using a New Augmented Reality Simulation Software for Breast Augmentation: A Prospective Study. J Clin Med. 2022 Jun 16;11(12):3464. doi: 10.3390/jcm11123464. PMID 35743534
• Song S, Parmeshwar N, Steiner G, Kim EA. Morphometric Analysis of Gender-affirming Breast Augmentation. Plast Reconstr Surg Glob Open. 2022 Nov 29;10(11):e4691. doi: 10.1097/GOX.0000000000004691. eCollection 2022 Nov. PMID 36467119
• Bin JM, Suminaite D, Benito-Kwiecinski SK, Kegel L, Rubio-Brotons M, Early JJ, Soong D, Livesey MR, Poole RJ, Lyons DA. Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons. Nat Commun. 2024 Feb 27;15(1):1790. doi: 10.1038/s41467-024-45908-6. PMID 38413580
• Clark IA, Mohammadi S, Callaghan MF, Maguire EA. Conduction velocity along a key white matter tract is associated with autobiographical memory recall ability. Elife. 2022 Sep 27;11:e79303. doi: 10.7554/eLife.79303. PMID 36166372
• Fricker FR, Lago N, Balarajah S, Tsantoulas C, Tanna S, Zhu N, Fageiry SK, Jenkins M, Garratt AN, Birchmeier C, Bennett DL. Axonally derived neuregulin-1 is required for remyelination and regeneration after nerve injury in adulthood. J Neurosci. 2011 Mar 2;31(9):3225-33. doi: 10.1523/JNEUROSCI.2568-10.2011. PMID 21368034

Идентификаторы

NCT: NCT07308275 · STUDINEUROTISASI

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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