Clinical trial NCT01591746: Botulinum Toxin A (Botox) in Tissue Expander Breast Reconstruction
Official title: Botulinum Toxin A in Tissue Expander Breast Reconstruction: A Double-Blinded Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Pain, Postoperative
BRCA1 Mutation
BRCA2 Mutation
Breast Diseases
Neoplasms
Keywords: Mastectomy
Mammaplasty
Breast reconstruction
Tissue expansion
Botulinum toxins, Type A
Quality of Life
Acellular dermal matrix
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Allergan
First posted: 2012-05-04
Enrollment: 131
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Each year, the number of breast cancer survivors who choose post-mastectomy breast reconstruction keeps rising. Among women who elect to pursue breast reconstruction, approximately 75% will choose prosthetic breast reconstruction. Implant-based breast reconstruction is frequently achieved in two-stages. The first stage consists of the placement of a tissue expander after mastectomy. This is followed by a period of biweekly tissue expansions that can last several months. In the second stage, the tissue expander is removed in a surgical procedure and replaced with a permanent breast implant. Tissue expansion is a well-established breast reconstruction technique characterized by high success rates and high patient satisfaction. Despite the well-recognized advantages of this successful breast reconstruction technique, the subpectoral placement of a tissue expander is associated with significant pain and discomfort in the immediate post-operative period and during the phase of tissue expansion. Pectoralis major muscle spasm is a frequently reported problem during tissue expansion. Legeby et al. recently showed that women who underwent prosthetic breast reconstruction had higher pain scores and took more analgesics that those who did not choose post-mastectomy reconstruction.

In the past 10 years, publications on the use of botulinum toxin A (BTX-A) for pain relief in a wide array of clinical conditions have increased tremendously. BTX-A is one of the neurotoxins produced by Clostridium botulinum bacteria. By reversibly inhibiting neurotransmitter release, BTX-A has both analgesic and paralytic properties. The analgesic action of BTX-A was initially thought to be related to its effects on muscular contraction. However, a recent in vitro study of embryonic rat dorsal neurons did confirm that BTX-A inhibits release of substance P, a neurotransmitter associated with pain and inflammatory reactions. The presence of analgesic properties of BTX-A is increasingly supported by several clinical observations: pain relief with BTX-A injections has been reported for migraine headaches, chronic pelvic, chronic tennis elbow, and post-operative pain control for lower limb lengthening correction, among others.

This aspect has never been studied in breast cancer survivors who elect to pursue breast reconstruction with tissue expanders. Furthermore, physical function outcomes are important to consider with BTX-A use because the link between temporary muscle paralysis and improvements in participation in daily activities is not a given.

The investigators propose to complete a double-blinded prospective randomized controlled trial of women undergoing unilateral and bilateral mastectomies with immediate placement of tissue expanders, to establish the efficacy and safety of BTX-A in alleviating pain and in improving physical well-being during the expansion period.

Detailed description: Consecutively enrolled eligible women will be randomized into one of two different treatment groups: 1) Group receiving BTX-A, and 2) Group receiving a placebo. All consenting subjects will be randomized to receive either a single injection of 100 units of BTX-A, or a placebo (saline water), during surgery in the pectoralis major muscle on the operated side once the mastectomy and the breast reconstruction have been completed. Expected duration of subject participation is 4 months.

Eligibility criteria: Inclusion Criteria:

* Women at least 18 years of age, who will undergo immediate unilateral or bilateral tissue expander breast reconstruction following therapeutic skin-sparing or nipple-sparing mastectomy
* Women at least 18 years of age, who will undergo immediate bilateral tissue expanders breast reconstruction following risk-reduction (prophylactic) skin-sparing or nipple-sparing mastectomy

Exclusion Criteria:

* Subjects who are unable to read or speak English
* Breast reconstruction using the latissimus dorsi flap combined with a tissue expander
* Documented diagnosis of chronic pain, upper limb spasticity, cervical dystonia, axillary hyperhidrosis, strabismus or blepharospasm
* Hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation
* Infection at the proposed site of injection
* Pre-existing neuromuscular disorders (including diagnosed myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis)
* Aminoglycosides intake at the time of surgery (these antibiotics can potentiate the effect of BTX-A)
* Women who are pregnant or breast feeding
* Presence of breast implants from previous breast surgery
* Reported use of Botox within 4 months prior to planned surgical date

Primary outcomes:
measure: Change From Baseline in Average Pain Scores Using a Numeric Pain Intensity Scale
timeFrame: preoperative visit, first postoperative visit (1-2 weeks post surgery)
measure: Physical Well-Being Using the BREAST-Q, Reconstruction Module
timeFrame: first post-operative visit (1-2 weeks post surgery)
Secondary outcomes:
measure: Initial Intraoperative Fill Volume in Milliliters (mL)
timeFrame: Single intra-operative measurement at first surgery
measure: Number of Tissue Expansion Visits
timeFrame: up to 24 weeks post-operatively
measure: Total Volume of Tissue Expansion
timeFrame: Up to 24 weeks post-operatively
measure: Rate of Reconstruction Failure
timeFrame: 6 months after first surgery
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Valerie Lemaine, MD
role: PRINCIPAL_INVESTIGATOR
References: