Clinical trial NCT03887377: The Efficacy and Molecular Mechanism of Botulinum Toxin in the Reduction of Breast Reduction Mammoplasty Scar Formation
Official title: The Efficacy and Molecular Mechanism of Botulinum Toxin in the Reduction of Breast Reduction Mammoplasty Scar Formation: A Prospective, Controlled, Randomized, Double-blinded Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Scar
Hypertrophic Scar
Mammary Disorder
Keywords: macromastia
botulinum toxin
scar prevention
scar formation
Lead sponsor: Henry Ford Health System
Sponsor class: OTHER
Collaborators: name: Galderma R&D
First posted: 2019-03-25
Enrollment: 22
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Undergoing breast reduction surgery
2. Does not meet any exclusion criteria
3. Female
4. \>18 years old
5. Willing to participate in study

Exclusion Criteria:

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

Primary outcomes:
measure: Modified Patient and Observer Scar Assessment Scale v2.0 (POSAS)
timeFrame: Photos will be reviewed at the 1 week follow surgery
measure: Modified Patient and Observer Scar Assessment Scale v2.0 (POSAS)
timeFrame: 4-8 weeks following surgery
measure: Modified Patient and Observer Scar Assessment Scale v2.0 (POSAS)
timeFrame: 6 month mark following surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
Study officials:
affiliation: Henry Ford Hospital
name: David Ozog, MD
role: PRINCIPAL_INVESTIGATOR
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