The Efficacy and Molecular Mechanism of Botulinum Toxin in the Reduction of Breast Reduction Mammoplasty Scar Formation

NCT ID: NCT03887377

Last Updated: 2025-06-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-10

Study Completion Date

2024-12-30

Brief Summary

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1. Test the ability of botulinum toxin type A, when injected into the surgical incision at the time of surgery, to decrease postoperative scar scores compared to control (normal saline) in a double-blinded randomized control trial.
2. Investigate the mechanism of BTXa effects of scar formation by measuring micro RNA profiles at two time points in the healing process.

Detailed Description

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Breast reduction mammoplasty is an increasingly popular procedure in this country due to not only the perceived cosmetic benefit of the procedure but additionally the improvement in musculoskeletal pain, headaches, sleeping difficulties, breathing, depression, self-esteem, and eating disorders. Despite these benefits, outcome satisfaction the typical inverted-T scar of the Wise pattern reduction has been limited by the resulting scar formation on the breast tissue. One study demonstrated that although 86% of patients were highly satisfied with their surgery, 65% were dissatisfied with their scars, with the majority of those dissatisfied , 65%, being bothered by the horizontal component of the scar. To address cosmetic outcomes of the procedure multiple techniques have been purposed in the literature including: superior pedicle technique, vertical mammoplasty, and circum-areolar breast reduction. By selectively injecting the horizontal component of the mammoplasty scar our analysis should be independent of surgeon surgical approach if it should include a vertical incisional scar. Aesthetic results of breast mammoplasty have also been attributed to analysis of breast meridian length, modifying areolar shape and most importantly tailoring or the medial inframammary crease. Tension across the inframammary crease requires appropriate shaping in order to reduce scar hypertrophy.

Mechanical stress from wound tension has been thought to play a major role in hypertrophic scar development. Cellular and biochemical studies have demonstrated that excessive forces on tissues are tightly linked to changes in the extracellular matrix such as the induction of wound fibrosis and inhibition of fibroblast apoptosis. Recently, botulinum toxin type A has been reported as a treatment agent to counteract these effects. Although its precise mechanism is not yet completely understood, botulinum toxin type A is thought to promote apoptosis of fibroblasts derived from hypertrophic scars, leading to reduced tensile forces. In an in vivo study, human hypertrophic scars treated with botulinum toxin type A had significantly reduced fibroblast proliferation compared to a control, and had synergistic effects with intralesional steroid injections, which is a commonly used treatment but with multiple adverse effects.

Botulinum toxin type A is a potent neurotoxin used in a wide scope of clinical settings, and has been injected for cosmetic purposes for more than two decades. Its clinical use specifically for hypertrophic scars, including those of the face, has recently been demonstrated. Furthermore, a randomized double-blinded split scar study has demonstrated the safety and efficacy of botulinum toxin type A injection into thyroidectomy scars for scar prevention. Although a well-controlled and designed study, its weaknesses include the difficult applicability of the Korean population to that of the United States, the relatively small number of patients included in the trial, the injection of botulinum toxin type A post-surgery instead of at the time of surgery (as the latter is often reported in other studies and is thought to be more beneficial). This protocol is designed to test the ability of botulinum toxin type A to improve post-surgical breast scarring in a randomized, double-blinded, controlled clinical trial at Henry Ford Hospital. It expands upon previous studies that have already demonstrated its safety and good tolerance profile, and will combine the expertise of the Dermatology department and Plastic surgeons. We will study breast reduction scars, as this will allow patients to serve as their own control group.

Conditions

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Scar Hypertrophic Scar Mammary Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Each patient will serve as their own control as one breast incision will be injected with botulinum toxin type A while the other will receive placebo.
Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors
The injector, patient, and outcome assessor will be blinded to the treatment side and placebo side of injection.

Study Groups

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Breast receiving botulinum toxin

Following reconstruction one horizontal incisional wound will be selected to receive a series of botulinum toxin injections along the wound.

Injection abobotulinum toxin at time of surgery, single injection time with 30 gauge needle superficially, dosage determined by length of scar 5-15U per cm

Group Type EXPERIMENTAL

Botulinum Toxins

Intervention Type DRUG

We will be comparing botulinum toxin following breast reduction surgery to placebo injection. We will then compare photos of each breast reduction scar at set intervals following surgery.

Breast receiving placebo

The other breast will be injected with bacteriostatic normal saline in a similar fashion to the other breast. The injector will be blinded to the contents of the syringe.

Group Type PLACEBO_COMPARATOR

Normal saline

Intervention Type OTHER

Normal saline will serve as the placebo control on the contralateral breast

Interventions

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Botulinum Toxins

We will be comparing botulinum toxin following breast reduction surgery to placebo injection. We will then compare photos of each breast reduction scar at set intervals following surgery.

Intervention Type DRUG

Normal saline

Normal saline will serve as the placebo control on the contralateral breast

Intervention Type OTHER

Other Intervention Names

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Dysport BTXa abobotulinumtoxinA Placebo

Eligibility Criteria

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Inclusion Criteria

1. Undergoing breast reduction surgery

Exclusion Criteria

3. Female
4. \>18 years old
5. Willing to participate in study


1. Allergy to botulinum toxin
2. Currently pregnant or breast feeding
3. Myasthenia gravis
4. Lambert-Eaton Myasthenic Syndrome
5. Amyopathic Lateral Sclerosis
6. Previous injection of botulinum toxin in the chest area within 6 months prior to enrollment
7. History of keloid or hypertrophic scar
8. History of previous breast surgery with scar affecting inframammary skin
9. Male Sex
10. Refusal to participate in the study
11. Unable to make follow up appointments up to 6 months
12. Less than 18 years of age
13. History of radiation to the breast
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Galderma R&D

INDUSTRY

Sponsor Role collaborator

Henry Ford Health System

OTHER

Sponsor Role lead

Responsible Party

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David M. Ozog

Chair of Department of Dermatology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David Ozog, MD

Role: PRINCIPAL_INVESTIGATOR

Henry Ford Hospital

Locations

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Henry Ford Health System

Detroit, Michigan, United States

Site Status

Countries

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United States

References

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Singh KA, Losken A. Additional benefits of reduction mammaplasty: a systematic review of the literature. Plast Reconstr Surg. 2012 Mar;129(3):562-570. doi: 10.1097/PRS.0b013e31824129ee.

Reference Type RESULT
PMID: 22090252 (View on PubMed)

Sprole AM, Adepoju I, Ascherman J, Gayle LB, Grant RT, Talmor M. Horizontal or vertical? an evaluation of patient preferences for reduction mammaplasty scars. Aesthet Surg J. 2007 May-Jun;27(3):257-62. doi: 10.1016/j.asj.2007.04.007.

Reference Type RESULT
PMID: 19341651 (View on PubMed)

Saleem L, John JR. Unfavourable results following reduction mammoplasty. Indian J Plast Surg. 2013 May;46(2):401-7. doi: 10.4103/0970-0358.118620.

Reference Type RESULT
PMID: 24501476 (View on PubMed)

Hidalgo DA. Improving safety and aesthetic results in inverted T scar breast reduction. Plast Reconstr Surg. 1999 Mar;103(3):874-86; discussion 887-9.

Reference Type RESULT
PMID: 10077078 (View on PubMed)

Wolfram D, Tzankov A, Pulzl P, Piza-Katzer H. Hypertrophic scars and keloids--a review of their pathophysiology, risk factors, and therapeutic management. Dermatol Surg. 2009 Feb;35(2):171-81. doi: 10.1111/j.1524-4725.2008.34406.x.

Reference Type RESULT
PMID: 19215252 (View on PubMed)

Niland S, Cremer A, Fluck J, Eble JA, Krieg T, Sollberg S. Contraction-dependent apoptosis of normal dermal fibroblasts. J Invest Dermatol. 2001 May;116(5):686-92. doi: 10.1046/j.1523-1747.2001.01342.x.

Reference Type RESULT
PMID: 11348456 (View on PubMed)

Chen CS. Mechanotransduction - a field pulling together? J Cell Sci. 2008 Oct 15;121(Pt 20):3285-92. doi: 10.1242/jcs.023507.

Reference Type RESULT
PMID: 18843115 (View on PubMed)

Gabbiani G. The myofibroblast in wound healing and fibrocontractive diseases. J Pathol. 2003 Jul;200(4):500-3. doi: 10.1002/path.1427.

Reference Type RESULT
PMID: 12845617 (View on PubMed)

Zhibo X, Miaobo Z. Botulinum toxin type A affects cell cycle distribution of fibroblasts derived from hypertrophic scar. J Plast Reconstr Aesthet Surg. 2008 Sep;61(9):1128-9. doi: 10.1016/j.bjps.2008.05.003. Epub 2008 Jun 13. No abstract available.

Reference Type RESULT
PMID: 18555763 (View on PubMed)

Zhibo X, Miaobo Z. Potential therapeutical effects of botulinum toxin type A in keloid management. Med Hypotheses. 2008 Oct;71(4):623. doi: 10.1016/j.mehy.2008.04.018. Epub 2008 Jun 4. No abstract available.

Reference Type RESULT
PMID: 18534768 (View on PubMed)

Xiao Z, Zhang F, Lin W, Zhang M, Liu Y. Effect of botulinum toxin type A on transforming growth factor beta1 in fibroblasts derived from hypertrophic scar: a preliminary report. Aesthetic Plast Surg. 2010 Aug;34(4):424-7. doi: 10.1007/s00266-009-9423-z. Epub 2009 Oct 3.

Reference Type RESULT
PMID: 19802513 (View on PubMed)

Chen HC, Yen CI, Yang SY, Chang CJ, Yang JY, Chang SY, Chuang SS, Hsiao YC. Comparison of Steroid and Botulinum Toxin Type A Monotherapy with Combination Therapy for Treating Human Hypertrophic Scars in an Animal Model. Plast Reconstr Surg. 2017 Jul;140(1):43e-49e. doi: 10.1097/PRS.0000000000003426.

Reference Type RESULT
PMID: 28654594 (View on PubMed)

Feily A, Fallahi H, Zandian D, Kalantar H. A succinct review of botulinum toxin in dermatology; update of cosmetic and noncosmetic use. J Cosmet Dermatol. 2011 Mar;10(1):58-67. doi: 10.1111/j.1473-2165.2010.00545.x.

Reference Type RESULT
PMID: 21332916 (View on PubMed)

Jablonka EM, Sherris DA, Gassner HG. Botulinum toxin to minimize facial scarring. Facial Plast Surg. 2012 Oct;28(5):525-35. doi: 10.1055/s-0032-1325641. Epub 2012 Oct 1.

Reference Type RESULT
PMID: 23027220 (View on PubMed)

Liu RK, Li CH, Zou SJ. Reducing scar formation after lip repair by injecting botulinum toxin. Plast Reconstr Surg. 2010 May;125(5):1573-1574. doi: 10.1097/PRS.0b013e3181d51404. No abstract available.

Reference Type RESULT
PMID: 20440184 (View on PubMed)

Zhibo X, Miaobo Z. Intralesional botulinum toxin type A injection as a new treatment measure for keloids. Plast Reconstr Surg. 2009 Nov;124(5):275e-277e. doi: 10.1097/PRS.0b013e3181b98ee7. No abstract available.

Reference Type RESULT
PMID: 20009818 (View on PubMed)

Kim YS, Lee HJ, Cho SH, Lee JD, Kim HS. Early postoperative treatment of thyroidectomy scars using botulinum toxin: a split-scar, double-blind randomized controlled trial. Wound Repair Regen. 2014 Sep-Oct;22(5):605-12. doi: 10.1111/wrr.12204. Epub 2014 Aug 26.

Reference Type RESULT
PMID: 24898579 (View on PubMed)

Larrabee WF Jr. Treatment of Facial Wounds with Botulinum Toxin A Improves Cosmetic Outcome in Primates. Plast Reconstr Surg. 2000 May;105(6):1954-1955. doi: 10.1097/00006534-200005000-00006. No abstract available.

Reference Type RESULT
PMID: 11242330 (View on PubMed)

Ziade M, Domergue S, Batifol D, Jreige R, Sebbane M, Goudot P, Yachouh J. Use of botulinum toxin type A to improve treatment of facial wounds: a prospective randomised study. J Plast Reconstr Aesthet Surg. 2013 Feb;66(2):209-14. doi: 10.1016/j.bjps.2012.09.012. Epub 2012 Oct 25.

Reference Type RESULT
PMID: 23102873 (View on PubMed)

Austin E, Koo E, Jagdeo J. The Cellular Response of Keloids and Hypertrophic Scars to Botulinum Toxin A: A Comprehensive Literature Review. Dermatol Surg. 2018 Feb;44(2):149-157. doi: 10.1097/DSS.0000000000001360.

Reference Type RESULT
PMID: 29401161 (View on PubMed)

Qu L, Liu A, Zhou L, He C, Grossman PH, Moy RL, Mi QS, Ozog D. Clinical and molecular effects on mature burn scars after treatment with a fractional CO(2) laser. Lasers Surg Med. 2012 Sep;44(7):517-24. doi: 10.1002/lsm.22055. Epub 2012 Jul 31.

Reference Type RESULT
PMID: 22907286 (View on PubMed)

Other Identifiers

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12373

Identifier Type: -

Identifier Source: org_study_id

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