Clinical trial NCT04794504: Investigating Temporalis and Masseter Botox Injection Before Orthognathic Surgery to Improve Postoperative Pain
Official title: Botulinum Toxin Type A Injected Into the Temporalis and Masseter Before Orthognathic Surgery to Improve Postoperative Pain
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Pain, Postoperative
Lead sponsor: Kingsway Oral & Maxillofacial Surgery
Sponsor class: OTHER
First posted: 2021-03-12
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: We will have two independent groups, one receiving botox injection, and another receiving saline injection.
Primary purpose: SUPPORTIVE_CARE

Brief summary: Jaw surgery has become a very successful way to improve the appearance and functional needs of patients. Like any surgery, jaw surgery comes with a host of possible issues that patients may experience during their recovery. Although some of the most serious complications, like infections, have reliable ways to alleviate the symptoms, patients must endure several other discomforting factors. These include postoperative pain and muscle spasms. Botox® is becoming an increasingly used intervention to treat muscle related disorders (including temporomandibular disorders and chronic myofascial pain) in the head and beck region. The investigators believe that by injecting Botox® into the muscles surrounding the surgical area, patients may experience a relief in tension-related discomfort, leading to less pain and better jaw function during recovery from surgery. Further, the side effects of Botox® are either very minimal or exceedingly rare. Ultimately, Botox® may serve as a great alleviating factor with few downsides, and represent a supplementary approach to helping mitigate postoperative pain.

Detailed description: Background and Rationale: Dentofacial deformities in the maxillofacial skeleton often require surgical intervention to correct aesthetic and functional deficiencies (Naran, Steinbacher, and Taylor, 2018). Often, patients suffer a number of postoperative complications, including postoperative pain and muscle spasms (Phillips, Blakey, and Jaskolka, 2008). While post-operative analgesics are used, regimens are often unsatisfactory in their ability to alleviate patient discomfort (Raschke et al. 2018). Botulinum toxin type A variants (BoNT-A; including Botox®) are becoming an increasingly used intervention to treat muscle-related disorders in the head and neck region, including migraines, myofascial pain, and temporomandibular joint disorders (Walker \& Dayan, 2014; Dodick et al, 2010; Mimeh, Fenech, Myers, \& Ghanem, 2019; Khalifeh et al., 2016, Machado et al., 2020). This occurs by inducing a flaccid muscle paralysis, which alleviates tension-related discomfort (Kwon et al., 2019). Thus by injecting Botox® into the muscles surrounding the surgical area preoperatively, patients may experience a relief in tension-related muscle pain and better jaw function during recovery from surgery. In addition to its great safety profile, where side effects are either very minimal or exceedingly rare, Botox® may serve as a great supplemental option to current postoperative analgesic regimens (Dressler et al., 2015, Yeh et al., 2018).

Objective: The primary objective of this study is to investigate whether preoperative injection of Botox® into the temporalis and masseter in patients undergoing bilateral sagittal split osteotomies (BSSO) will improve pain scores and spasms in the immediate 2 week, as well as 6 week, postoperative periods. Additionally, patients will be followed 5 years from the time of surgery to look for indicators of relapse, including infection and hardware failure.

Research question: Can injecting Botox® into facial muscles 2 weeks prior to orthognathic surgery result in decreased pain and muscle spasms postoperatively?

Methods: The investigators plan to do a pilot study involving patients undergoing BSSO to evaluate postoperative pain scores and muscle spasms. There is a lack of evidence investigating post-operative pain management in orthognathic surgery using Botox®, thus the studies outlined in this proposal will serve as a pilot project. However, to guide sample size determination, another study investigating incobotulinumtoxinA, one of the variants of botulinum toxin with a similar potency profile to Botox® (Scaglione, 2016), was used. This product has been used as a therapeutic treatment for temporomandibular disorders to manage myofascial pain (Patel, Lerner, and Blitzer, 2017). For these studies, based on previous experiences, a pain difference of 15% was determined to be clinically significant. Assuming a normal distribution, a continuous pain outcome, with an ⍺-level of 0.05, and a power of 80%, the investigators estimate 32 patients/group will need to be enrolled to capture this difference.

This will be a double-blinded study. The patients, principal investigators and trained observers analyzing the data will be blinded to the two groups. Half of the patients will receive BoNT-A injections (Botox® Therapeutic by Allergan, Inc), with the other half receiving 0.9% normal saline injections as a control cohort. Injections for both cohorts will be done two weeks preoperatively. Patients will be randomly designated to one of the two groups by a research assistant at Kingsway Oral and Maxillofacial surgery not named to the investigative team. Patients will be randomized into two groups using a 2:2 randomized block design. A computer-generated algorithm developed the randomization sequence which allowed for allotment of each patient into either group 1 (indicating Botox® injection) or 2 (indicating saline injection). Patients will not be informed of the group they belong to, only that they will be injected with either Botox® or saline; the surgical assistants will prepare either the Botox® injection or the 0.9% normal saline injection. The injection will be given to the surgeons performing the procedures with no knowledge of which patients will be getting which injection.

BSSO will be performed by Dr. Clayton Davis, Dr. Kevin Lung, and Dr. Matt Fay according to Kinsgway Oral and Maxillofacial Surgery clinical protocols. Patients will be asked to complete a numerical response scale (NRS) daily for 14 consecutive days, starting on postoperative day 1. Each day, the highest pain rating will be recorded as a whole number on a 0-10 scale. In the same 2 week timeframe, patients will also be asked to track any muscle spasms daily in the form of a "yes/no" question. At the 6 week follow-up appointment, patients will be asked to rate their pain at the current time on the NRS, and will be asked about further muscle spasms in the 2-6 week postoperative period in the form of a "yes/no" question. In order to track pain scores and muscle spasms, a paper questionnaire will be distributed to all patients. In addition to scoring pain daily on the NRS, patients will be asked to track: the time of the most severe pain, medications that were taken to help with the pain, pain intensity 1 hour after medication was taken, location of the pain, activities that led to onset of pain, and occurrence of muscle spasms. At the 2 week follow-up appointment, patients will bring back their paper copy of the questionnaire. Hardware failure and infection will be documented in the patient's chart, and will be viewed retrospectively study 5 years from now in the form of chart reviews of all study participants.

Eligibility criteria: Inclusion Criteria:

* All patients between the ages 18 and 65 undergoing BSSO at Kingsway Oral and Maxillofacial Surgery are eligible to participate in the study, provided they do not fit any of the exclusion criteria.

Exclusion Criteria:

-Patient with history of chronic pain conditions including, but not limited to: myofascial pain:

* TMD, internal disc derangement, and TMJ osteoarthritis
* chronic migraines/tension type headaches and cervical pain
* generalized anxiety disorder
* diagnosed neuropathic pain (neuralgias)
* Mentally incompetent individuals
* History of botulinum toxin use for cosmetic and therapeutic uses
* History of trauma or previous orthognathic surgery
* Patients with hypersensitivity to BoNT-A
* Pregnant women
* Nursing women

Primary outcomes:
measure: Investigating a role of Botox intramuscular injection in reducing postoperative pain scores in orthognathic surgery patients 2 and 6 weeks after surgery
timeFrame: Analysis of this outcome will be ongoing throughout the study duration, and will end with the final orthognathic surgery patient completing their 2 week pain assessment
Secondary outcomes:
measure: Investigating a role of Botox intramuscular injection in reducing postoperative muscle spams orthognathic surgery patients 2 weeks after surgery
timeFrame: Analysis of this outcome will be ongoing throughout the study duration, and will end with the final orthognathic surgery patient completing their 6 week pain assessment
measure: Investigating a role of Botox intramuscular injection in reducing hardware failure and rates of infection 5 years postoperatively
timeFrame: Analysis of this outcome will be ongoing throughout the study duration, and will end 5 years from the final participants day of surgery
measure: Investigating a role of Botox intramuscular injection in reducing postoperative pain scores in orthognathic surgery patients 6 weeks after surgery
timeFrame: Analysis of this outcome will be ongoing throughout the study duration, and will end with the final orthognathic surgery patient completing their 6 week pain assessment
Other outcomes:
Locations:
Study officials:
References:
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