Botulinum Toxin A (Botox) in Tissue Expander Breast Reconstruction

NCT01591746 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 11-001687
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Average Pain Scores Using a Numeric Pain Intensity Scale

  The numeric pain intensity scale (NPIS) will be completed at the preoperative visit and again at the first postoperative visit. The NPIS is a visual analog scale (VAS) commonly used to assess clinical pain. Subjects are asked to rate their pain on a scale from 0 to 10, where 0 is no pain and 10 is the worst pain imaginable.

  preoperative visit, first postoperative visit (1-2 weeks post surgery)

• Physical Well-Being Using the BREAST-Q, Reconstruction Module

  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. The Reconstruction module Physical Well-Being scale has questions on the function and participation in activities before and after breast reconstruction. For this study, subjects were asked to answer 16 questions on how often they experienced each symptom, using score of 1 to 5, where 1 was none of the time and 5 was very often. Answers from these questions were combined to provide a total physical well-being score (for a total possible range of 16-80) for each patient at each visit. Lower scores reflected fewer symptoms and higher satisfaction where higher scores reflected more symptoms and less satisfaction.

  first post-operative visit (1-2 weeks post surgery)

Secondary Outcomes (4)

• Initial Intraoperative Fill Volume in Milliliters (mL)

  Single intra-operative measurement at first surgery

• Number of Tissue Expansion Visits

  up to 24 weeks post-operatively

• Total Volume of Tissue Expansion

  Up to 24 weeks post-operatively

• Rate of Reconstruction Failure

  6 months after first surgery

Study Arms (2)

Group A - Botulinum Toxin Type A

EXPERIMENTAL

100 Units of Botulinum toxin A diluted in 5 mL 0.9% Sodium Chloride (NaCl) in the pectoralis major muscle in each operated breast

Drug: Botulinum Toxin Type A

Group B - Placebo

PLACEBO COMPARATOR

5 mL 0.9% NaCl injection to the pectoralis major muscle in each operated breast

Drug: Placebo

Interventions

Botulinum Toxin Type A DRUG

Also known as: BOTOX

Group A - Botulinum Toxin Type A

Placebo DRUG

5 mL 0.9% NaCl solution to mimic Botulinum Toxin Type A

Also known as: Sodium chloride solution

Group B - Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• Allergan: collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Breast Neoplasms; Pain, Postoperative; Breast Diseases; Neoplasms

Interventions

Botulinum Toxins, Type A; Sodium Chloride

Condition Hierarchy (Ancestors)

Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

A practice change from patients receiving paravertebral blocks preoperatively to intraoperative field blocks with liposomal bupivacaine;data not collected on postoperative oral narcotic consumption;study designed to detect 25% decrease in pain score.

Results Point of Contact

• Title: Dr. Valerie Lemaine, MD, MPH
• Organization: Mayo Clinic

lemaine.valerie17@gmail.com

507-284-2736

Study Officials

• Valerie Lemaine, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 13, 2012
• First Posted: May 4, 2012
• Study Start: August 1, 2012
• Primary Completion: July 18, 2017
• Study Completion: July 18, 2017
• Last Updated: October 10, 2019
• Results First Posted: October 10, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)