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

NCT03887377 | Completed Phase 2 FDA Drug

• 1 other identifier: 12373
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

1. 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. 2.Investigate the mechanism of BTXa effects of scar formation by measuring micro RNA profiles at two time points in the healing process.

Conditions

Scar; Hypertrophic Scar; Mammary Disorder

Keywords

macromastia; botulinum toxin; scar prevention; scar formation

Outcome Measures

Primary Outcomes (3)

• Modified Patient and Observer Scar Assessment Scale v2.0 (POSAS)

  Two blinded dermatologists will make the objective clinical assessments separately using a modified POSAS Patient and Observer Scar Assessment Scale v2.0 It includes assessing the vascularity, pigmentation, thickness, relief, and surface area from a scale from 1 to 10. Pliability, which is included in the original scale, will be excluded for this study given the use of photographs for assessment. The scale also includes the patient's opinion of their own scar, which includes pain, pruritis, color, stiffness, thickness, irregularity from a scale from 1 to 10.Independent objective review of scar photos will be graded on a scale 1-10. 1 is normal skin. 10 is worst scar imaginable.

  Photos will be reviewed at the 1 week follow surgery

• Modified Patient and Observer Scar Assessment Scale v2.0 (POSAS)

  Two blinded dermatologists will make the objective clinical assessments separately using a modified POSAS Patient and Observer Scar Assessment Scale v2.0 It includes assessing the vascularity, pigmentation, thickness, relief, and surface area from a scale from 1 to 10. Pliability, which is included in the original scale, will be excluded for this study given the use of photographs for assessment. The scale also includes the patient's opinion of their own scar, which includes pain, pruritis, color, stiffness, thickness, irregularity from a scale from 1 to 10.Independent objective review of scar photos will be graded on a scale 1-10. 1 is normal skin. 10 is worst scar imaginable. These scores will be compared to the 1 week time point.

  4-8 weeks following surgery

• Modified Patient and Observer Scar Assessment Scale v2.0 (POSAS)

  Two blinded dermatologists will make the objective clinical assessments separately using a modified POSAS Patient and Observer Scar Assessment Scale v2.0 It includes assessing the vascularity, pigmentation, thickness, relief, and surface area from a scale from 1 to 10. Pliability, which is included in the original scale, will be excluded for this study given the use of photographs for assessment. The scale also includes the patient's opinion of their own scar, which includes pain, pruritis, color, stiffness, thickness, irregularity from a scale from 1 to 10.Independent objective review of scar photos will be graded on a scale 1-10. 1 is normal skin. 10 is worst scar imaginable. These scores will be compared to the 1 week and the 4-8 weeks time point.

  6 month mark following surgery

Study Arms (2)

Breast receiving botulinum toxin

EXPERIMENTAL

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

Drug: Botulinum Toxins

Breast receiving placebo

PLACEBO COMPARATOR

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.

Other: Normal saline

Interventions

Botulinum Toxins 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.

Also known as: Dysport, BTXa, abobotulinumtoxinA

Breast receiving botulinum toxin

Normal saline OTHER

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

Also known as: Placebo

Breast receiving placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Undergoing breast reduction surgery

You may not qualify if:

• Female
• \>18 years old
• Willing to participate in study
• Allergy to botulinum toxin
• Currently pregnant or breast feeding
• Myasthenia gravis
• Lambert-Eaton Myasthenic Syndrome
• Amyopathic Lateral Sclerosis
• Previous injection of botulinum toxin in the chest area within 6 months prior to enrollment
• History of keloid or hypertrophic scar
• History of previous breast surgery with scar affecting inframammary skin
• Male Sex
• Refusal to participate in the study
• Unable to make follow up appointments up to 6 months
• Less than 18 years of age

Sponsors & Collaborators

• Henry Ford Health System: lead
• Galderma R&D: collaborator

Study Sites (1)

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Related Publications (21)

• 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.

  PMID: 22090252 RESULT

• 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.

  PMID: 19341651 RESULT

• 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.

  PMID: 24501476 RESULT

• 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.

  PMID: 10077078 RESULT

• 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.

  PMID: 19215252 RESULT

• 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.

  PMID: 11348456 RESULT

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

  PMID: 18843115 RESULT

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

  PMID: 12845617 RESULT

• 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.

  PMID: 18555763 RESULT

• 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.

  PMID: 18534768 RESULT

• 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.

  PMID: 19802513 RESULT

• 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.

  PMID: 28654594 RESULT

• 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.

  PMID: 21332916 RESULT

• 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.

  PMID: 23027220 RESULT

• 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.

  PMID: 20440184 RESULT

• 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.

  PMID: 20009818 RESULT

• 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.

  PMID: 24898579 RESULT

• 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.

  PMID: 11242330 RESULT

• 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.

  PMID: 23102873 RESULT

• 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.

  PMID: 29401161 RESULT

• 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.

  PMID: 22907286 RESULT

MeSH Terms

Conditions

Cicatrix; Cicatrix, Hypertrophic; Breast Diseases; Gigantomastia

Interventions

Botulinum Toxins; abobotulinumtoxinA; Saline Solution

Condition Hierarchy (Ancestors)

Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• David Ozog, MD

  Henry Ford Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: The injector, patient, and outcome assessor will be blinded to the treatment side and placebo side of injection.
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair of Department of Dermatology

Model Details: 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.

Study Record Dates

• First Submitted: February 20, 2019
• First Posted: March 25, 2019
• Study Start: June 10, 2019
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: June 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)