Sensory Restoration Surgery for Breast Reconstruction

Overseen By Gedge D Rosson, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Johns Hopkins University

Disqualifiers: Diabetic neuropathy, Thyroid disorders, Alcoholism, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

156 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have conditions like diabetic neuropathy or are taking medications that cause neuropathy, you may not be eligible to participate.

What data supports the effectiveness of the treatment DIEP Flap Neurotization for breast sensory restoration?

Research shows that neurotization techniques, which involve connecting nerves to improve sensation, lead to better and faster sensory recovery in breast reconstructions using the DIEP flap. Patients who had immediate neurotized DIEP flap reconstructions reported improved sensation and higher satisfaction compared to those with delayed reconstructions. ^{1 2 3 4 5}

Is sensory restoration surgery for breast reconstruction safe?

Research indicates that breast sensory restoration using DIEP flap neurotization is generally safe, with minimal complications reported. The procedure is described as rapid and simple, with promising results in terms of sensory return and patient satisfaction. ^{1 2 3 4 5}

How is the DIEP Flap Neurotization treatment different from other breast reconstruction treatments?

DIEP Flap Neurotization is unique because it focuses on restoring sensation to the reconstructed breast by connecting nerves, which improves sensory recovery compared to non-innervated flaps. This approach is a simple procedure with minimal risk and has shown promising results in enhancing patient satisfaction by achieving better sensory return. ^{1 2 3 4 5}

What is the purpose of this trial?

Common goals of breast reconstruction include obtaining satisfactory breast symmetry, softness, and appropriate size and shape. Advances in surgical techniques have prompted a new goal: achieving breast sensation after reconstructive surgery. This desire has led the surgical community to investigate operative techniques for achieving this goal. However, few studies have examined the effectiveness of breast sensory restoration. Sensory nerves are nerves responsible for sensation from skin. When a sensory nerve is cut, sensation is lost to the area supplied by the nerve. In the case of Breast reconstruction this involves the nerves supplying the skin overlying breast(s). 'Neurotization' refers to regeneration of the nerve after it has been cut. This means that the cut nerve is being repaired in order to restore its function. In Neurotization this repair is carried out using a new "source". In this case, the investigators want to restore function of the nerves that supply the skin overlying the breast(s). The investigators will be performing breast reconstruction using tissue from the patient's abdomen and transferring it to the chest wall to repair the mastectomy defect. Sensory function is restored by using the nerve that supplies the skin of this abdominal tissue (i.e the new "source") that is being transferred and attaching it to a nerve in the chest wall. The Avance® Nerve graft is a nerve graft material that has been produced by Axogen, Inc. The graft is made by processing donated human nerves. This graft is used during neurotization to bridge the gap and join the nerve from the abdominal tissue to the nerve in the chest wall. The use of the graft helps the body to attach these 2 nerves and improves nerve repair. When neurotization is done without the nerve graft there is a possibility that the surgeon may require extra nerve material to join the 2 nerves. Traditionally, in this case the surgeon would have to obtain a separate donor nerve from another part of the patient's body. This technique carries the risk of complications to part of the body that the separate donor nerve was obtained from - loss of sensation, infection or neuroma formation (an abnormal growth of nerve tissue that can cause pain, burning or tingling sensation, numbness). The Avance nerve graft avoids the need for the additional donor nerve and the possible complications associated with it. The Avance® Nerve Graft is currently being used in some women during breast reconstruction surgery, however the effectiveness of this procedure in improving the restoration of sensation has not been proven. Women undergoing reconstruction of one breast and at the same time using the women's own tissue as part of standard clinical care, may join.

Research Team

Gedge D Rosson, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for women over 18 who are undergoing unilateral mastectomy and breast reconstruction using their own abdominal tissue (DIEP flap). They must understand the study and consent to participate. Excluded are pregnant or lactating women, those with previous reconstructions or lumpectomy with radiation, recurrent breast cancer, and conditions like diabetic neuropathy or severe peripheral neuropathy.

Inclusion Criteria

The patient is aware of the nature of her malignancy if a malignancy has been diagnosed; understands the study purpose, requirements, and risks; and is able and willing to sign an informed consent.

I am planning to have a mastectomy and DIEP flap reconstruction at Johns Hopkins.

I will be assigned to one of two breast reconstruction methods, with or without nerve connection.

Exclusion Criteria

I do not have conditions like diabetic neuropathy, thyroid disorders, or severe nerve damage from other causes.

Pregnant or lactating women will be excluded from this study.

I have not had breast reconstruction or lumpectomy with radiation before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Treatment

Breast reconstruction using DIEP flap neurotization with or without Avance® Nerve Graft

Immediate (surgery duration)

1 visit (in-person for surgery)

Follow-up

Participants are monitored for breast sensation and quality of life improvements

24 months

Regular follow-up visits at 6, 12, 18, and 24 months

Treatment Details

Interventions

• DIEP Flap Neurotization

Trial Overview The trial tests sensory restoration in reconstructed breasts. Participants will be randomly assigned to receive DIEP flap reconstruction with neurotization using Avance® Nerve Graft (to connect nerves from abdomen to chest) or without neurotization. The goal is to see if sensation can be restored more effectively with the nerve graft.

Participant Groups

Group I: Neurotized Patients Experimental Treatment 1 Intervention

Neurotization will be performed at the time of reconstruction.

Group II: Non-Neurotized Patients Active Control 1 Intervention

No Neurotization will be performed at the time of reconstruction.

DIEP Flap Neurotization is already approved in United States, European Union for the following indications:

Approved in United States as DIEP Flap Neurotization for:

• Breast reconstruction after mastectomy
• Restoration of breast sensation

Approved in European Union as DIEP Flap Neurotization for:

• Breast reconstruction after mastectomy
• Restoration of breast sensation

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Axogen Corporation

Industry Sponsor

Trials

11

Recruited

5,600+

Findings from Research

In a study of 30 breast cancer patients undergoing DIEP flap reconstruction, significant sensory recovery was observed at 6 and 12 months post-surgery, indicating that the procedure allows for progressive return of sensation without the need for nerve repair.

The best sensory recovery occurred in the inferior lateral quadrant of the flap, suggesting that while some areas recover better than others, overall, the DIEP flap provides satisfactory sensory outcomes, allowing surgeons to potentially reduce operative time by not focusing on nerve coaptation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective computerized analyses of sensibility in breast reconstruction with non-reinnervated DIEP flap. Santanelli, F., Longo, B., Angelini, M., et al.[2022]

Neurotization techniques used during immediate DIEP flap breast reconstructions significantly improve breast sensation and sensory recovery compared to delayed reconstructions, highlighting their efficacy in enhancing patient outcomes.

The procedure is described as rapid and simple with minimal morbidity, making it a promising option for restoring breast sensation and increasing patient satisfaction after mastectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-mastectomy sensory recovery and restoration. Hamilton, KL., Kania, KE., Spiegel, AJ.[2021]

The study of 29 women who underwent breast reconstruction with DIEAP flaps showed that these flaps can spontaneously reinnervate, providing measurable sensation in 29 out of 30 flaps, despite no direct sensory nerve repair.

Pressure sensitivity was significantly better in the inferomedial part of the flap compared to other areas, suggesting that nerve ingrowth occurs from the sides of the flap, enhancing sensory recovery in specific regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spontaneous reinnervation of deep inferior epigastric artery perforator flaps after secondary breast reconstruction. Tindholdt, TT., Tønseth, KA.[2022]

In a study of 67 patients undergoing DIEP flap breast reconstruction, those who received innervated flaps showed significantly better sensory recovery in the reconstructed breast compared to those with noninnervated flaps, indicating the effectiveness of nerve coaptation.

The sensory recovery at the donor site was not negatively affected by the nerve coaptation, suggesting that this technique can enhance breast sensation without compromising the donor area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nerve Coaptation Improves the Sensory Recovery of the Breast in DIEP Flap Breast Reconstruction. Beugels, J., Bijkerk, E., Lataster, A., et al.[2021]

Patients who underwent skin-sparing mastectomies with nonburied DIEP flap reconstruction experienced significantly better inner breast region sensation at 6 months post-surgery compared to their baseline levels, indicating quicker sensory recovery.

In contrast, those with buried DIEP flaps from nipple-sparing mastectomies showed no significant improvement in sensation at 6 months, with recovery to baseline levels occurring later, around 24 months postoperatively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study Comparing Sensation in Buried Versus Nonburied Deep Inferior Epigastric Perforator Flaps. Lu Wang, M., Qin, N., Chadab, TM., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Prospective computerized analyses of sensibility in breast reconstruction with non-reinnervated DIEP flap. [2022]

2. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Post-mastectomy sensory recovery and restoration. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Spontaneous reinnervation of deep inferior epigastric artery perforator flaps after secondary breast reconstruction. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Nerve Coaptation Improves the Sensory Recovery of the Breast in DIEP Flap Breast Reconstruction. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

A Pilot Study Comparing Sensation in Buried Versus Nonburied Deep Inferior Epigastric Perforator Flaps. [2023]