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

December 15, 2025 updated by: Mohamad Rachadian Ramadan, Fakultas Kedokteran Universitas Indonesia

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

28

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Mohamad Rachadian Ramadan, MD., MRBS.
  • Phone Number: +62881082855557
  • Email: rachadian@ui.ac.id

Study Locations

  • Indonesia
    • Jakarta Special Capital Region
      • Jakarta Pusat, Jakarta Special Capital Region, Indonesia, 10430
        • dr. Ciptomangunkusumo National Hospital - Faculty of Medicine Universitas Indonesia
        • Contact:
        • Principal Investigator:
          • Mohamad Rachadian Ramadan, MD, MRBS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Non-Neurotized Group
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
Breast reconstruction is performed using autologous tissue without nerve coaptation or neurotization, according to standard surgical practice.
Experimental: Neurotized Group
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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Breast Sensation assessed by using Semmes-Weinstein Monofilament testing
Time Frame: 1, 3 and 6 months after Neurotization
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
Time Frame: 1, 3 and 6 months after Neurotization
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neuregulin 1 Expression
Time Frame: During procedure and 6 months after surgery
NRG1 expression quantified by ELISA from flap tissue
During procedure and 6 months after surgery
Nerve Cross-sectional Area
Time Frame: Measured during neurotization procedure
Nerve cross-sectional area measured via histomorphometry/histopathology using the recipient nerve of the direct neurotization method
Measured during neurotization procedure
Breast Morphometry
Time Frame: Before surgery and 1, 3, 6 months after surgery
Breast morphometry assessed using a validated AR/3D application
Before surgery and 1, 3, 6 months after surgery
Intraepidermal Nerve Fibre Density (IENFD)
Time Frame: During procedure and 6 months after surgery
IENFD quantified by counting PGP9.5-positive intraepidermal fibers per mm of epidermal length. Flap skin tissue samples will be taken using 3 mm punch biopsy
During procedure and 6 months after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fakultas Kedokteran Universitas Indonesia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 15, 2025

Primary Completion (Estimated)

February 15, 2027

Study Completion (Estimated)

April 15, 2027

Study Registration Dates

First Submitted

December 15, 2025

First Submitted That Met QC Criteria

December 15, 2025

First Posted (Actual)

December 29, 2025

Study Record Updates

Last Update Posted (Actual)

December 29, 2025

Last Update Submitted That Met QC Criteria

December 15, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDINEUROTISASI

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared due to concerns regarding participant confidentiality and the potential risk of re-identification in a small surgical trial with detailed clinical and biomarker data.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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