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

Study Overview
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Brief Summary
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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. 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.

Official Title
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The Efficacy and Molecular Mechanism of Botulinum Toxin in the Reduction of Breast Reduction Mammoplasty Scar Formation: A Prospective, Controlled, Randomized, Double-blinded Study

Conditions
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Scar, Hypertrophic Scar, Mammary Disorder

Intervention / Treatment
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* Drug: Botulinum Toxins
* Other: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergoing breast reduction surgery Does not meet any exclusion criteria Female >18 years old Willing to participate in study Exclusion Criteria: 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 History of radiation to the breast

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Breast receiving botulinum toxin<br>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<br>* 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.<br>* Other names: abobotulinumtoxinA;|
| Placebo Comparator: Breast receiving placebo<br>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<br>* Normal saline will serve as the placebo control on the contralateral breast<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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botulinum toxin, scar prevention, macromastia, scar formation