Clinical trial NCT06930378: Improvement in Breast Skin Sensibility After Breast Reconstruction: a Comparison of 3 Surgical Techniques
Official title: Sensory Restoration in DIEP Free Flaps for Post-Mastectomy Breast Reconstruction After Breast Cancer: Comparing Non-sensitized Standard Technique to Direct Nerve Suture and to Autograft: A Three-arm, Randomized, Double-blinded Superiority Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer Surgery
Reconstruction Breast Surgery
Sensitization
DIEP Flap Breast Reconstruction
Keywords: free flap
breast reconstruction
autologous-based reconstruction
neurotization
sensory recovery
post-mastectomy sensation
autologous breast reconstruction
DIEP flap
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2025-04-16
Enrollment: 63
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Three-arm, Randomised, Double-blinded Superiority Trial
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if nerve sutures in free flap breast reconstruction can optimize sensibility in the reconstructed breast in patients opting for DIEP flap breast reconstruction due to breast cancer or genetic conditions. Affected women 18 to 80 years old can be included. The main question is:

If a nerve suture was carried out, can pressure be felt better on the reconstructed breast after 12 months? If a nerve suture was carried out, will better sensibility and quality of life be felt and perceived (questionnaire) at 12 and 24 months after the initial operation ? Researchers will compare two different nerve suture techniques and no nerve suture to one another to see if and which nerve suture optimizes sensibility.

Participants will have regular visits and follow-up controls, during which

* their sensibility will be tested multimodally,
* they will fill out questionnaires
* skin biopsies will be taken.

Detailed description: Breast reconstruction with autologous tissue is one of the most important methods: The DIEP (deep inferior epigastric artery perforator) flap is today's workhorse in autologous reconstruction. Routinely, the arteries and veins of the donor- and recipient sites are connected, but not the nerves. The sensory recovery is an undervalued aspect despite the disadvantages of insensate flaps. Connection of the abdominal flap skin's nerves to the breast region's nerves allows sensitized reconstruction. The research project aims to make sensitized flap-based breast reconstruction the standard method by proving its superiority, using the sensory testing with Semmes-Weinstein-Monofilament (pressure threshold) as the primary outcome measured before surgery and 12 months post-surgery. Therefore, patients will be randomized in three groups:

1. sensitization with direct nerve suture or
2. autograft or
3. no sensitization. Moreover, no previous studies have analyzed the potential changes in flap skin with proteomics, thus justifying our secondary objective.

The hypothesis is that flaps with nerve suture(s) have better sensibility. The main outcome will be the sensory testing (pressure threshold). As secondary outcomes the questionnaire will show the patients' quality of life, and the proteomic analysis, should, according to our hypothesis, show that quantity and expression of the proteins of flap skin with nerve suture are closer to normal skin than without nerve suture.

Eligibility criteria: A) Pilot study

Inclusion criteria:

* 18-80 years old
* having received DIEP flap breast reconstruction with a flap not completely buried
* having given written informed consent for participating in the study

Exclusion criteria:

* postoperative radiotherapy on the flap
* neurological conditions as diabetic neuropathy, alcoholism or any other severe underlying peripheral neuropathy including chemotherapy-induced neuropathy or neuropathy induced by other medications
* active smoking
* language barrier
* pregnancy or lactating women

B) Main study

Inclusion Criteria:

* 18 to 80 years old
* having given written informed consent for participating in the study
* receiving immediate or delayed unilateral DIEP breast reconstruction with a DIEP flap which will not be completely buried

Exclusion Criteria:

* autologous reconstruction where the flap is completely buried
* patients in need of both-sided reconstruction (double DIEP)
* postoperative radiotherapy on the flap
* neurological conditions as diabetic neuropathy, alcoholism, or any other severe underlying peripheral neuropathy including chemotherapy-induced neuropathy or neuropathy induced by other medications
* active smoking
* language barrier
* pregnancy at time of planned DIEP flap surgery and lactation

Primary outcomes:
measure: Semmes-Weinstein-Monofilament-Test
timeFrame: At 12-months-follow-up
Secondary outcomes:
measure: Change in breast sensation
timeFrame: day-1/1week/3/6/12/24 months postop
measure: Sensory recovery to DIEP flap
timeFrame: 12 months postop
measure: Change in breast sensation
timeFrame: day-1/1week/3/6/12/24 months postop
measure: Sensory recovery to DIEP flap
timeFrame: 12 months postop
measure: Change in breast sensation
timeFrame: day-1/1week/3/6/12/24 months postop
measure: Sensory recovery to DIEP flap
timeFrame: 12 months postop
measure: Change in breast sensation
timeFrame: day-1/1week/3/6/12/24 months postop
measure: Sensory recovery to DIEP flap
timeFrame: 12 months postop
measure: Change in breast sensation
timeFrame: day-1/1week/3/6/12/24 months postop
measure: Sensory recovery to DIEP flap
timeFrame: 12 months postop
measure: Change in breast sensation
timeFrame: day-1/1week/3/6/12/24 months postop
measure: Breast-specific health-related QoL
timeFrame: 12 months postop
measure: Breast-specific health-related QoL (change over time)
timeFrame: Day -1, 12 &24 months postop
measure: Operative time
timeFrame: At time of 1st operation
measure: Changes to DIEP flap skin
timeFrame: A) Pilot study Postoperatively at any time of follow-up-interventions. B) Main study At time of 1st operation and at 6-months-follow-up
measure: Sensory recovery to DIEP flap
timeFrame: 12 months postop
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: Geneva University Hospitals
Study officials:
affiliation: University Hospital, Geneva
name: Patricia E Engels, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Puonti HK, Broth TA, Soinila SO, Hallikainen HK, Jaaskelainen SK. How to Assess Sensory Recovery After Breast Reconstruction Surgery? Clin Breast Cancer. 2017 Oct;17(6):471-485. doi: 10.1016/j.clbc.2017.04.011. Epub 2017 Apr 29.
citation: Blondeel PN, Demuynck M, Mete D, Monstrey SJ, Van Landuyt K, Matton G, Vanderstraeten GG. Sensory nerve repair in perforator flaps for autologous breast reconstruction: sensational or senseless? Br J Plast Surg. 1999 Jan;52(1):37-44. doi: 10.1054/bjps.1998.3011.
citation: Spiegel AJ, Salazar-Reyes H, Izaddoost S, Khan FN. A novel method for neurotization of deep inferior epigastric perforator and superficial inferior epigastric artery flaps. Plast Reconstr Surg. 2009 Jan;123(1):29e-30e. doi: 10.1097/PRS.0b013e3181905564. No abstract available.
citation: Bijkerk E, Beugels J, van Kuijk SMJ, Lataster A, van der Hulst RRWJ, Tuinder SMH. Clinical Relevance of Sensory Nerve Coaptation in DIEP Flap Breast Reconstruction Evaluated Using the BREAST-Q. Plast Reconstr Surg. 2022 Nov 1;150(5):959e-969e. doi: 10.1097/PRS.0000000000009617. Epub 2022 Aug 22.
citation: 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.
citation: Ducic I, Yoon J, Momeni A, Ahcan U. Anatomical Considerations to Optimize Sensory Recovery in Breast Neurotization with Allograft. Plast Reconstr Surg Glob Open. 2018 Nov 7;6(11):e1985. doi: 10.1097/GOX.0000000000001985. eCollection 2018 Nov.
citation: Spiegel AJ, Menn ZK, Eldor L, Kaufman Y, Dellon AL. Breast Reinnervation: DIEP Neurotization Using the Third Anterior Intercostal Nerve. Plast Reconstr Surg Glob Open. 2013 Dec 6;1(8):e72. doi: 10.1097/GOX.0000000000000008. eCollection 2013 Nov.
citation: Beugels J, Cornelissen AJM, van Kuijk SMJ, Lataster A, Heuts EM, Piatkowski A, Spiegel AJ, van der Hulst RRWJ, Tuinder SMH. Sensory Recovery of the Breast following Innervated and Noninnervated DIEP Flap Breast Reconstruction. Plast Reconstr Surg. 2019 Aug;144(2):178e-188e. doi: 10.1097/PRS.0000000000005802.
citation: Hamilton KL, Kania KE, Spiegel AJ. Post-mastectomy sensory recovery and restoration. Gland Surg. 2021 Jan;10(1):494-497. doi: 10.21037/gs.2020.03.22.
citation: Bijkerk E, van Kuijk SMJ, Lataster A, van der Hulst RRWJ, Tuinder SMH. Breast sensibility in bilateral autologous breast reconstruction with unilateral sensory nerve coaptation. Breast Cancer Res Treat. 2020 Jun;181(3):599-610. doi: 10.1007/s10549-020-05645-y. Epub 2020 Apr 28.