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

NCT07308275 | Not Yet Recruiting DMC

• 1 other identifier: STUDINEUROTISASI
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 2.Does neurotization enhance patient-reported sensory outcomes and quality of life, as assessed by the BREAST-Q Sensation Module?
3. 3.Neuregulin-1 (NRG1) expression in flap tissue biopsy;
4. 4.Cross-sectional area of the recipient nerve fibres;
5. 5.Breast morphometry measured at baseline and follow-up;
6. 6.Intraepidermal nerve fibre density (IENFD) on skin biopsy.
7. 7.Neurotized autologous breast reconstruction using fully autologous graft components, or
8. 8.Standard (non-neurotized) autologous breast reconstruction.
9. 9.Autologous breast reconstruction with or without direct neurotization as part of their planned cancer surgery.
10. 10.Sensory testing using Semmes-Weinstein monofilaments at baseline, 1, 3, and 6 months.
11. 11.Completion of BREAST-Q questionnaires evaluating breast sensation, symptoms, and quality of life at each follow-up visit.

Conditions

Breast Reconstruction After Mastectomy; Neurotization; Sensory Function; Mastectomy and Breast Reconstruction; Peripheral Nerve Regeneration; Quality of Life (QOL)

Keywords

breast neurotization; mastectomy; breast sensory; quality of life

Outcome Measures

Primary Outcomes (2)

• Breast Sensation assessed by using Semmes-Weinstein Monofilament testing

  SWM thresholds at nine standardized points on the reconstructed breast will be measured using calibrated monofilaments, categorized into levels of normal touch, diminished light touch, diminished protective sensation, loss of protective sensation, and deep pressure only.

  1, 3 and 6 months after Neurotization

• Patient's Quality of Life assessed by using BREAST-Q® Sensation Module

  The patient reported outcomes will be recorded in BREAST-Q® Sensation Module to capture the sensation, breast symptoms, and quality of life impact of sensation loss.

  1, 3 and 6 months after Neurotization

Secondary Outcomes (4)

• Neuregulin 1 Expression

  During procedure and 6 months after surgery

• Nerve Cross-sectional Area

  Measured during neurotization procedure

• Breast Morphometry

  Before surgery and 1, 3, 6 months after surgery

• Intraepidermal Nerve Fibre Density (IENFD)

  During procedure and 6 months after surgery

Study Arms (2)

Non-Neurotized Group

ACTIVE COMPARATOR

Participants assigned to this arm are women undergoing mastectomy who are eligible for standard autologous breast reconstruction without neurotization.

Procedure: Autologous Breast Reconstruction without Neurotization

Neurotized Group

EXPERIMENTAL

Participants assigned to this arm are women undergoing mastectomy who are eligible for autologous breast reconstruction with planned direct neurotization using fully autologous components.

Procedure: Autologous Breast Reconstruction With Direct Neurotization

Interventions

Autologous Breast Reconstruction With Direct Neurotization PROCEDURE

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

Neurotized Group

Autologous Breast Reconstruction without Neurotization PROCEDURE

Breast reconstruction is performed using autologous tissue without nerve coaptation or neurotization, according to standard surgical practice.

Non-Neurotized Group

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fakultas Kedokteran Universitas Indonesia: lead

Study Sites (1)

dr. Ciptomangunkusumo National Hospital - Faculty of Medicine Universitas Indonesia

Jakarta Pusat, Jakarta Special Capital Region, 10430, Indonesia

Location

Related Publications (18)

• 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.

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• 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 BACKGROUND

• 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.

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• 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.

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  PMID: 21368034 BACKGROUND

• Stassart RM, Fledrich R, Velanac V, Brinkmann BG, Schwab MH, Meijer D, Sereda MW, Nave KA. A role for Schwann cell-derived neuregulin-1 in remyelination. Nat Neurosci. 2013 Jan;16(1):48-54. doi: 10.1038/nn.3281. Epub 2012 Dec 9.

  PMID: 23222914 BACKGROUND

• Dellon ES, Crone S, Mouery R, Dellon AL. Comparison of the Semmes-Weinstein monofilaments with the Pressure-Specifying Sensory Device. Restor Neurol Neurosci. 1993 Jan 1;5(5):323-6. doi: 10.3233/RNN-1993-55602.

  PMID: 21551718 BACKGROUND

• Voineskos SH, Klassen AF, Cano SJ, Pusic AL, Gibbons CJ. Giving Meaning to Differences in BREAST-Q Scores: Minimal Important Difference for Breast Reconstruction Patients. Plast Reconstr Surg. 2020 Jan;145(1):11e-20e. doi: 10.1097/PRS.0000000000006317.

  PMID: 31577663 BACKGROUND

• Gallo L, Chu JJ, Shamsunder MG, Hatchell A, Patel AR, Godwin K, Hernandez M, Pusic AL, Nelson JA, Voineskos SH. Best Practices for BREAST-Q Research: A Systematic Review of Study Methodology. Plast Reconstr Surg. 2022 Sep 1;150(3):526e-535e. doi: 10.1097/PRS.0000000000009401. Epub 2022 Jun 24.

  PMID: 35749737 BACKGROUND

• Ramadan MR, Rifai DA, Atmodiwirjo P, Panigoro SS, Mukarramah DA, Sobri FB, Jurisman A, Djohan R. Indonesian Translation and Cultural Adaptation of the BREAST-Q Reconstruction Module. Plast Reconstr Surg Glob Open. 2025 Apr 21;13(4):e6705. doi: 10.1097/GOX.0000000000006705. eCollection 2025 Apr.

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• Shiah E, Laikhter E, Comer CD, Manstein SM, Bustos VP, Bain PA, Lee BT, Lin SJ. Neurotization in Innervated Breast Reconstruction: A Systematic Review of Techniques and Outcomes. J Plast Reconstr Aesthet Surg. 2022 Sep;75(9):2890-2913. doi: 10.1016/j.bjps.2022.06.006. Epub 2022 Jun 17.

  PMID: 35872020 BACKGROUND

• Tecce MG, Desai AA, Christopher A, Cunning J, Rios-Diaz AJ, Morris MP, et al. 6. Breast Flap Neurotization After Autologous Free Flap Breast Reconstruction: A Prospective Trial. In: PRS Global Open [Internet]. 2022. Available from: http://journals.lww.com/prsgo

  BACKGROUND

• Shyu S, Chang TN, Lu JC, Chen CF, Cheong DC, Kao SW, Kuo WL, Huang JJ. Breast neurotization along with breast reconstruction after nipple sparing mastectomy enhances quality of life and reduces denervation symptoms in patient-reported outcome: a prospective cohort study. Int J Surg. 2025 May 1;111(5):3235-3247. doi: 10.1097/JS9.0000000000002331.

  PMID: 40072353 BACKGROUND

• Jagasia PM, Bagdady K, Jordan SW, Howard MA, Fracol ME. Meta-analysis of Objective Sensory Outcomes From 764 Breasts Shows Superior Sensation of Autologous Reconstruction With Neurotization. Plast Reconstr Surg Glob Open. 2025 May 6;13(5):e6751. doi: 10.1097/GOX.0000000000006751. eCollection 2025 May.

  PMID: 40330161 BACKGROUND

MeSH Terms

Interventions

Nerve Transfer

Intervention Hierarchy (Ancestors)

Neurosurgical Procedures; Surgical Procedures, Operative

Central Study Contacts

Mohamad Rachadian Ramadan, MD., MRBS.

CONTACT

+62881082855557; rachadian@ui.ac.id

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: dr. Mohamad Rachadian Ramadan, B.Med.Sc, Sp.B.P.R.E, Subsp.M.O.(K), MRBS

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: December 29, 2025
• Study Start: December 15, 2025
• Primary Completion (Estimated): February 15, 2027
• Study Completion (Estimated): April 15, 2027
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)