Botulinum Toxin A (Botox) in Tissue Expander Breast Reconstruction

Study Description

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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 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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer; Pain, Postoperative; BRCA1 Mutation; BRCA2 Mutation; Breast Diseases; Neoplasms	Drug: Botulinum Toxin Type A; Drug: Sodium Chloride Solution	Phase 3

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	141 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Supportive Care
Official Title:	Botulinum Toxin A in Tissue Expander Breast Reconstruction: A Double-Blinded Randomized Controlled Trial
Actual Study Start Date :	August 2012
Actual Primary Completion Date :	July 18, 2017
Actual Study Completion Date :	July 18, 2017

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Group A; Botulinum Toxin A	Drug: Botulinum Toxin Type A; 100 Units of Botulinum toxin A diluted in 5 mL 0.9% Sodium Chloride in the pectoralis major muscle in each operated breast.; Other Name: BOTOX
Placebo Comparator: Group B; Placebo	Drug: Sodium Chloride Solution; 5 mL 0.9% NaCl injection to the pectoralis major muscle in each operated breast.

Outcome Measures

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Primary Outcome Measures :

1. Change from Baseline in average pain scores using a numeric pain intensity scale [ Time Frame: Pre-operative visit, first post-operative visit, subsequent plastic surgery appointments/expansion visits for a period of approximately 4 months. ]
   The numeric pain intensity scale (NPIS) will be completed at various time frames. The NPIS is a visual analog scale commonly used to assess clinical pain.
2. Change from Baseline in Physical Well-Being using the BREAST-Q Physical Well-Being scale [ Time Frame: Pre-operative visit, first post-operative visit, subsequent plastic surgery appointments/expansion visits for a period of approximately 4 months. ]
   The Physical Well-Being scale of the BREAST-Q, reconstruction module, will be used for this purpose. The BREAST-Q is a validated patient-reported outcome measure to accurately assess quality of life and patient satisfaction.

Secondary Outcome Measures :

1. Initial percent volume expansion intra-operatively [ Time Frame: Single intra-operative measurement at first surgery ]
   The amount of initial intraoperative fill volume in the tissue expander at the time of surgery divided by the manufacturers recommended total tissue expander volume will be measured.
2. Rate of tissue expansion [ Time Frame: Up to 24 weeks ]
   Measurement of expansion volume at each tissue expansion and number of tissue expansions completed.
3. Rate of reconstruction failure [ Time Frame: At 6 months after first surgery ]
   Determine the rate of tissue expander removal.
4. Incidence of side effects attributable to the injection of BTX-A at doses of 100 units and 200 units. [ Time Frame: First 30 days postoperatively ]
   All serious adverse events will be recorded and reported. Minor adverse events and unusual complications encountered during the postoperative period will be carefully recorded.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion:

1. 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.
2. 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:

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

Contacts and Locations

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Locations

United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

Investigators

Principal Investigator:	Valerie Lemaine, MD	Mayo Clinic

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Valerie Lemaine, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier:	NCT01591746 History of Changes
Other Study ID Numbers:	11-001687
First Posted:	May 4, 2012
Last Update Posted:	October 19, 2017
Last Verified:	October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Valerie Lemaine, Mayo Clinic:

Mastectomy; Mammaplasty; Breast reconstruction; Tissue expansion	Botulinum toxins, Type A; Quality of Life; Acellular dermal matrix

Additional relevant MeSH terms:

Pain, Postoperative; Breast Diseases; Pain; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Signs and Symptoms; Skin Diseases; Botulinum Toxins; Botulinum Toxins, Type A	onabotulinumtoxinA; abobotulinumtoxinA; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents