Breast CancerPhase 3NCT01591746
Botulinum Toxin A (Botox) in Tissue Expander Breast Reconstruction
A Phase 3 study testing Botulinum Toxin Type A in people with Breast Cancer and Pain, Postoperative, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breast Cancer, Pain, Postoperative, BRCA1 Mutation
- What is being tested?
- Botulinum Toxin Type A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 131 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2012to 18 Jul 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Botulinum Toxin A in Tissue Expander Breast Reconstruction: A Double-Blinded Randomized Controlled Trial
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.
Read more
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.
Read the 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.
- Conditions
- Breast Cancer, Pain, Postoperative, BRCA1 Mutation, BRCA2 Mutation, Breast Diseases, Neoplasms
- Being tested
- Botulinum Toxin Type A, Placebo
- Keywords
- Mastectomy, Mammaplasty, Breast reconstruction, Tissue expansion, Botulinum toxins, Type A, Quality of Life, Acellular dermal matrix
- Medical subject headings
- Breast Neoplasms, Pain, Postoperative, Breast Diseases, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called BOTOX
PlaceboDrug
Also called Sodium chloride solution
5 mL 0.9% NaCl solution to mimic Botulinum Toxin Type A
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: first post-operative visit (1-2 weeks post surgery)
Secondary outcomes (4)
Initial Intraoperative Fill Volume in Milliliters (mL)
The amount of initial intraoperative fill volume in milliliters (mL) in the tissue expander at the time of surgery divided by the manufacturers recommended total tissue expander volume will be measured. Each breast will be measured separately.
Measured: Single intra-operative measurement at first surgery
Number of Tissue Expansion Visits
The total number of tissue expansion visits completed post-operatively.
Measured: up to 24 weeks post-operatively
Total Volume of Tissue Expansion
Measurement of total expansion volume in milliliters (mL).
Measured: Up to 24 weeks post-operatively
Rate of Reconstruction Failure
The rate of reconstruction failure will be measured by the number of subjects who have tissue expander removal.
Measured: 6 months after first surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2012 (estimated)
- Study startAug 2012
- Primary completion18 Jul 2017
- Study completion18 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Allergan
- Responsible party
- Principal investigator, Valerie Lemaine, Mayo Clinic
- Investigators
- Valerie Lemaine, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01591746
- Sponsor's protocol ID
- 11-001687
- Status last verified
- Sep 2019
- First submitted
- 13 Apr 2012
- Last updated
- 10 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Botulinum Toxin A in Tissue Expander Breast Reconstruction: A Double-Blinded Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT01591746
- Acronym / sponsor ID
- 11-001687
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Allergan
- Study start
- Aug 2012 (actual)
- Primary completion
- 18 Jul 2017 (actual)
- Study completion
- 18 Jul 2017 (actual)
- First posted
- 4 May 2012 (estimated)
- Results
- Posted 10 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A - Botulinum Toxin Type A | Experimental | Drug: Botulinum Toxin Type A100 Units of Botulinum toxin A diluted in 5 mL 0.9% Sodium Chloride (NaCl) in the pectoralis major muscle in each operated breast |
| Group B - Placebo | Placebo comparator | Drug: Placebo5 mL 0.9% NaCl injection to the pectoralis major muscle in each operated breast |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Botulinum Toxin Type AAlso: BOTOX | Drug | Group A - Botulinum Toxin Type A |
| PlaceboAlso: Sodium chloride solution5 mL 0.9% NaCl solution to mimic Botulinum Toxin Type A | Drug | Group B - Placebo |
Primary outcome
Change From Baseline in Average Pain Scores Using a Numeric Pain Intensity Scale
Time frame: preoperative visit, first postoperative visit (1-2 weeks post surgery)
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.
Physical Well-Being Using the BREAST-Q, Reconstruction Module
Time frame: first post-operative visit (1-2 weeks post surgery)
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.
4 secondary outcomes
Initial Intraoperative Fill Volume in Milliliters (mL)
Time frame: Single intra-operative measurement at first surgery
Number of Tissue Expansion Visits
Time frame: up to 24 weeks post-operatively
Total Volume of Tissue Expansion
Time frame: Up to 24 weeks post-operatively
Rate of Reconstruction Failure
Time frame: 6 months after first surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Valerie Lemaine, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Botulinum Toxin Type A in people with Breast Cancer and Pain, Postoperative, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Average Pain Scores Using a Numeric Pain Intensity Scale (time frame: preoperative visit, first postoperative visit (1-2 weeks post surgery)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2019.