ClinicalTrials.gg
Not yet recruitingNCT07308275Updated Dec 29, 2025

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

An interventional study of Autologous Breast Reconstruction With Direct Neurotization and Autologous Breast Reconstruction without Neurotization in Breast Reconstruction After Mastectomy, Neurotization and Mastectomy and Breast Reconstruction, sponsored by Fakultas Kedokteran Universitas Indonesia. Not yet recruiting at 1 site in Indonesia. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-12-29.

Sponsored by Fakultas Kedokteran Universitas Indonesia · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
28
Allocation
Randomized
Ages
18 Years and older
Sex
Female
01

Study 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. 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.

02

Conditions studied

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

Keywords

  • breast neurotization
  • mastectomy
  • breast sensory
  • quality of life
03

In context

Lead sponsor

Fakultas Kedokteran Universitas Indonesia is the lead sponsor of 36 studies on the registry; 6 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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 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 .

Exclusion criteria

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.
Terms in these criteria, in plain language(2)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Adjuvant and neoadjuvant

Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Outcomes assessor)
Enrollment
28 participants (estimated)

Study arms

  • 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

  • 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

Interventions

  • ProcedureAutologous 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

  • ProcedureAutologous Breast Reconstruction without Neurotization

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

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 1, 3 and 6 months after Neurotization

  2. 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.

    Time frame: 1, 3 and 6 months after Neurotization

Secondary outcomes

  1. Neuregulin 1 Expression

    NRG1 expression quantified by ELISA from flap tissue

    Time frame: During procedure and 6 months after surgery

  2. Nerve Cross-sectional Area

    Nerve cross-sectional area measured via histomorphometry/histopathology using the recipient nerve of the direct neurotization method

    Time frame: Measured during neurotization procedure

  3. Breast Morphometry

    Breast morphometry assessed using a validated AR/3D application

    Time frame: Before surgery and 1, 3, 6 months after surgery

  4. Intraepidermal Nerve Fibre Density (IENFD)

    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

    Time frame: During procedure and 6 months after surgery

07

Study locations

1 site
  • dr. Ciptomangunkusumo National Hospital - Faculty of Medicine Universitas Indonesia
    Jakarta Pusat, Jakarta Special Capital Region 10430, Indonesia
    • Ayu PB Sarena, MD, MPH · Contactayusarena16@gmail.com · +6285121316121
    • Mohamad Rachadian Ramadan, MD, MRBS · Principal investigator
08

References and documents

Publications

  • 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. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 21368034 ↗
  • 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. PubMed 23222914 ↗
  • 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. PubMed 21551718 ↗
  • 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. PubMed 31577663 ↗
  • 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. PubMed 35749737 ↗
  • 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. PubMed 40264905 ↗
  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PubMed 33538338 ↗
  • 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. PubMed 35872020 ↗
  • 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
  • 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. PubMed 40072353 ↗
  • 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. PubMed 40330161 ↗

Individual participant data

Plan to share: No — 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.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Start is estimated for Dec 2025; primary completion for Feb 2027, 14 months later.

How these figures are worked out, and which studies are left out of them.

Registered
Dec 15, 2025
First posted
Dec 29, 2025
StartEst.
Dec 15, 2025
Primary completionEst.
Feb 15, 2027
CompletionEst.
Apr 15, 2027
Last update
Dec 29, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Dec 29, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07308275
Lead sponsor
Fakultas Kedokteran Universitas Indonesia
Responsible party
Mohamad Rachadian Ramadan (dr. Mohamad Rachadian Ramadan, B.Med.Sc, Sp.B.P.R.E, Subsp.M.O.(K), MRBS, Fakultas Kedokteran Universitas Indonesia) — Principal investigator
First posted
Dec 29, 2025
Start date
Dec 15, 2025 (estimated)
Primary completion
Feb 15, 2027 (estimated)
Completion
Apr 15, 2027 (estimated)
Last update
Dec 29, 2025

Study contacts

Mohamad Rachadian Ramadan, MD., MRBS.
Contact
rachadian@ui.ac.id
+62881082855557

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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