SynkinesisPhase 4NCT07295288
Botox Injections in Non-Cranial Nerve VII Innervated Muscles for Facial Synkinesis
A Phase 4 study testing Botulinum Toxin Type A Injection [Botox] in people with Synkinesis, run by Vanderbilt University Medical Center.
Trial summary
Facial synkinesis is a condition that occurs following facial nerve (CN7) injury, typically secondary to Bell's palsy, trauma, surgery (e.g., acoustic neuroma resection), or malignancy. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Synkinesis
- What is being tested?
- Botulinum Toxin Type A Injection [Botox]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2026to 30 Jun 2027
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age > 18 years.
- Current diagnosis of facial synkinesis due to facial nerve paralysis/paresis.
- Scheduled to undergo BT injection for management of facial synkinesis.
- Have undergone > 3 prior BT injection sessions at VUMC for facial synkinesis.
- Able to read and understand English.
- Symptoms of neck tightness, jaw tightness, or headaches.
Who cannot join
- Cognitive impairment that would preclude the ability to provide informed consent
- Unable to read text on a written survey or computer screen
About this study
Official title: Investigating the Efficacy of Botox Injections in Non-Cranial Nerve VII Innervated Muscles for Facial Synkinesis Management
Facial synkinesis is a condition that occurs following facial nerve (CN7) injury, typically secondary to Bell's palsy, trauma, surgery (e.g., acoustic neuroma resection), or malignancy. Synkinesis is due to aberrant regeneration of the facial nerve, where axons regrow improperly and result in misdirected innervation of facial muscles. This results in involuntary, uncoordinated muscle movements, where activation of one muscle group triggers unintended contractions in others. Standard treatment of facial synkinesis involves botulinum toxin (BT) injections into muscles controlled by CN7 to reduce these unwanted movements. However, patients often anecdotally report that adding BT injections into non-CN7 innervated muscle groups, such as the masseter and temporalis muscles, improve their synkinesis symptoms. This study therefore aims to assess whether adding BT injections to non-CN7 innervated muscle groups, specifically the masseter and temporalis muscle, can improve treatment outcomes for people with facial synkinesis. This study will use a crossover design, where each participant will serve as their own control to compare treatment effects. In the first treatment arm, patients will receive only their standard BT injections into muscle groups controlled by CN7 - no other muscles will be treated. In the second treatment arm, will receive the same standard BT injections in CN7 muscles, plus additional injections into masseter and temporalis muscles. Patients will be randomized to a specific treatment arm at their first visit. At their second visit, they will be randomized to the other treatment arm, in standard crossover study design. Pre- and post-treatment surveys will be collected to assess the benefit of adding non-CN7 muscle groups.
Read the detailed description
Facial synkinesis is a debilitating condition that occurs following injury to the facial nerve (CN7). It results from misdirected nerve regrowth, leading to involuntary, often conflicting muscle movements (e.g., eye closure during smiling or neck muscle tightening). This causes functional impairments (e.g., cheek biting, eating difficulties, reduced visibility), cosmetic concerns, and increased rates of anxiety and depression. Facial synkinesis has been reported in the literature to affect up to 75% of patients with facial nerve injury.
Chemodenervation of facial muscle groups using targeted BT injections has become a mainstay treatment for facial synkinesis. Typically, BT is selectively injected into hyperfunctioning CN7-innervated muscles on the injured side to allow for relaxation and restoration of organized muscle contraction. BT may also be injected into CN7-innervated muscles on the contralateral non-affected side, to improve facial symmetry. These injections have been shown across numerous studies to be safe, improve facial symmetry, and decrease severity of synkinesis symptoms. Injections are typically preformed every 3-6 months, depending on the needs of the patient and duration of injection benefit.
While synkinesis is thought to predominantly affect CN7 innervated muscles, in our clinical experience many patients also experience painful contracture of non-CN7 innervated muscles, such as the temporalis or master muscles. We therefore routinely inject these muscle groups with BT during patients synkinesis treatments. While patients anecdotally report that injection of non-CN7 innervated muscles improve their synkinesis symptoms in our clinical practice, this has not been systematically studied in the literature. This study therefore aims to investigate whether extending BT injections to non-cranial nerve 7-innervated muscles, specifically the masseter and temporalis muscle, can enhance outcomes for facial synkinesis.
Since participants are already receiving BT as standard care, the study introduces no additional risks, focusing only on adjusting injection targets within their existing treatment. This research addresses a critical gap in managing synkinesis, where current treatments are limited, and could lead to refined protocols that enhance patient quality of life by reducing symptoms and improving facial symmetry. The potential benefits-improved function, aesthetics, and mental well-being-outweigh the minimal risks, as the intervention aligns with established, safe practices.
- Conditions
- Synkinesis
- Being tested
- Botulinum Toxin Type A Injection [Botox]
- Keywords
- botulinum toxin
- Medical subject headings
- Synkinesis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Botulinum Toxin Type A Injection [Botox]Drug
Patients will receive standard of care synkinesis treatment. Depending on the treatment arm, they will receive additional botox injections to temporalis and masseter muscle groups which will only be injected on the ipsilateral side to the facial nerve injury. Decision to include the temporalis and/or masseter muscles will be based on each patients response to screening questions regarding jaw pain/tightness or headaches.
| Study group | Role | What they receive |
|---|---|---|
| Even MRN | Other | Patients with MRNs ending in an even number will undergo their standard BT injections (CN7 muscle groups only) + non-CN7 muscle groups at their first treatment session, followed by standard BT injections alone at their second treatment session. Receives: Drug: Botulinum Toxin Type A Injection [Botox] |
| Odd MRN | Other | Patients with MRNs that end in an odd number will undergo the reverse injection process (standard BT injections alone at first treatment session, followed by standard BT injections + non-CN7 muscle groups at their second treatment session). Receives: Drug: Botulinum Toxin Type A Injection [Botox] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Synkinesis Assessment Questionnaire (SAQ)
This 9-item questionnaire assesses functional status (hyperactive and/or inappropriately active facial muscles) related to facial synkinesis and is already given at each clinic visit as a routine part of clinical practice. The survey is well validated for evaluating synkinesis symptoms in patients with facial nerve injury.
SAQ scale: 1 = seldom or not at all, 2 = occasionally, or very mildly, 3 = sometimes, or mildly, 4 = most of the time, or moderately, 5 = all the time, or severely
Measured: Pre-treatment and repeated 5 weeks post-treatment
Headache Impact Test (HIT-6)
This 6-item questionnaire seeks to understand the severity of headaches and impact on every-day quality of life. The survey is widely validated for assessing headache symptom and burden. We plan to add in 3 additional questions to this survey including 1) how often do you experience headaches (1 = never or rarely, 2 = 1-2 days a week, 3 = 3-4 days a week, 4 = nearly every day), 2) on a scale of 1-10 (10 = most severe) how severe are your headaches, and 3) I feel as if my Botox injections improved my headaches (Y/N).
HIT-6 Scale: 1 = Never 2 = Rarely 3 = Sometimes 4 = Very often 5 = Always
Measured: Pre-treatment and repeated 5 weeks post-treatment
Temporomandibular Disorder Questionnare (TMD-7)
This 7-item questionnaire assesses symptoms related to temporomandibular mandibular joint (TMJ) disorder. It asks about jaw pain, tightness, clicking and difficulty eating, among other things. We plan to add in 3 additional questions to this survey including 1) how often do you experience jaw pain/tightness (1 = never or rarely, 2 = 1-2 days a week, 3 = 3-4 days a week, 4 = nearly every day), 2) on a scale of 1-10 (10 = most severe) how severe is your jaw pain/tightness, and 3) I feel as if my Botox injections improved my jaw pain/tightness (Y/N).
TMD-7 Scale: 1 = Rarely or Never 2 = A few times a month 3 = Once or Twice a Week 4 = Nearly Every Day
Measured: Pre-treatment and repeated 5 weeks post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2025
- Study start1 Jul 2026 (estimated)
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Why it stopped: Unable to secure funding for TMJ and masseter Botox.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SynkinesisStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- The study design is a prospective crossover study. Patients who meet eligibility criteria and wish to proceed with the study will be randomized into two groups based on their MRN numbers. Patients with MRNs ending in an even number will undergo their standard BT injections (CN7 muscle groups only) + non-CN7 muscle groups at their first treatment session, followed by standard BT injections alone at their second treatment session. Patients with MRNs that end in an odd number will undergo the reverse injection process (standard BT injections alone at first treatment session, followed by standard BT injections + non-CN7 muscle groups at their second treatment session).
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Priyesh Patel, Vanderbilt University Medical Center
- Investigators
- Priyesh Patel, MD, Principal investigator, VUMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07295288
- Sponsor's protocol ID
- 251490
- Status last verified
- Nov 2026
- First submitted
- 7 Dec 2025
- Last updated
- 3 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Efficacy of Botox Injections in Non-Cranial Nerve VII Innervated Muscles for Facial Synkinesis Management
- ClinicalTrials.gov ID
- NCT07295288
- Acronym / sponsor ID
- 251490
- Conditions
- Synkinesis
- Keywords
- botulinum toxin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Unable to secure funding for TMJ and masseter Botox.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- 1 Jul 2026 (estimated)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 19 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Facial synkinesis is a condition that occurs following facial nerve (CN7) injury, typically secondary to Bell's palsy, trauma, surgery (e.g., acoustic neuroma resection), or malignancy. Synkinesis is due to aberrant regeneration of the facial nerve, where axons regrow improperly and result in misdirected innervation of facial muscles. This results in involuntary, uncoordinated muscle movements, where activation of one muscle group triggers unintended contractions in others. Standard treatment of facial synkinesis involves botulinum toxin (BT) injections into muscles controlled by CN7 to reduce these unwanted movements. However, patients often anecdotally report that adding BT injections into non-CN7 innervated muscle groups, such as the masseter and temporalis muscles, improve their synkinesis symptoms. This study therefore aims to assess whether adding BT injections to non-CN7 innervated muscle groups, specifically the masseter and temporalis muscle, can improve treatment outcomes for people with facial synkinesis. This study will use a crossover design, where each participant will serve as their own control to compare treatment effects. In the first treatment arm, patients will receive only their standard BT injections into muscle groups controlled by CN7 - no other muscles will be treated. In the second treatment arm, will receive the same standard BT injections in CN7 muscles, plus additional injections into masseter and temporalis muscles. Patients will be randomized to a specific treatment arm at their first visit. At their second visit, they will be randomized to the other treatment arm, in standard crossover study design. Pre- and post-treatment surveys will be collected to assess the benefit of adding non-CN7 muscle groups.
Detailed description
Facial synkinesis is a debilitating condition that occurs following injury to the facial nerve (CN7). It results from misdirected nerve regrowth, leading to involuntary, often conflicting muscle movements (e.g., eye closure during smiling or neck muscle tightening). This causes functional impairments (e.g., cheek biting, eating difficulties, reduced visibility), cosmetic concerns, and increased rates of anxiety and depression. Facial synkinesis has been reported in the literature to affect up to 75% of patients with facial nerve injury.
Chemodenervation of facial muscle groups using targeted BT injections has become a mainstay treatment for facial synkinesis. Typically, BT is selectively injected into hyperfunctioning CN7-innervated muscles on the injured side to allow for relaxation and restoration of organized muscle contraction. BT may also be injected into CN7-innervated muscles on the contralateral non-affected side, to improve facial symmetry. These injections have been shown across numerous studies to be safe, improve facial symmetry, and decrease severity of synkinesis symptoms. Injections are typically preformed every 3-6 months, depending on the needs of the patient and duration of injection benefit.
While synkinesis is thought to predominantly affect CN7 innervated muscles, in our clinical experience many patients also experience painful contracture of non-CN7 innervated muscles, such as the temporalis or master muscles. We therefore routinely inject these muscle groups with BT during patients synkinesis treatments. While patients anecdotally report that injection of non-CN7 innervated muscles improve their synkinesis symptoms in our clinical practice, this has not been systematically studied in the literature. This study therefore aims to investigate whether extending BT injections to non-cranial nerve 7-innervated muscles, specifically the masseter and temporalis muscle, can enhance outcomes for facial synkinesis.
Since participants are already receiving BT as standard care, the study introduces no additional risks, focusing only on adjusting injection targets within their existing treatment. This research addresses a critical gap in managing synkinesis, where current treatments are limited, and could lead to refined protocols that enhance patient quality of life by reducing symptoms and improving facial symmetry. The potential benefits-improved function, aesthetics, and mental well-being-outweigh the minimal risks, as the intervention aligns with established, safe practices.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The study design is a prospective crossover study. Patients who meet eligibility criteria and wish to proceed with the study will be randomized into two groups based on their MRN numbers. Patients with MRNs ending in an even number will undergo their standard BT injections (CN7 muscle groups only) + non-CN7 muscle groups at their first treatment session, followed by standard BT injections alone at their second treatment session. Patients with MRNs that end in an odd number will undergo the reverse injection process (standard BT injections alone at first treatment session, followed by standard BT injections + non-CN7 muscle groups at their second treatment session).
| Arm | Type | Receives |
|---|---|---|
| Even MRN | Other | Drug: Botulinum Toxin Type A Injection [Botox]Patients with MRNs ending in an even number will undergo their standard BT injections (CN7 muscle groups only) + non-CN7 muscle groups at their first treatment session, followed by standard BT injections alone at their second treatment session. |
| Odd MRN | Other | Drug: Botulinum Toxin Type A Injection [Botox]Patients with MRNs that end in an odd number will undergo the reverse injection process (standard BT injections alone at first treatment session, followed by standard BT injections + non-CN7 muscle groups at their second treatment session). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age > 18 years.
- Current diagnosis of facial synkinesis due to facial nerve paralysis/paresis.
- Scheduled to undergo BT injection for management of facial synkinesis.
- Have undergone > 3 prior BT injection sessions at VUMC for facial synkinesis.
- Able to read and understand English.
Key exclusion criteria (2 listed)
- Cognitive impairment that would preclude the ability to provide informed consent
- Unable to read text on a written survey or computer screen
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 A Injection [Botox]Patients will receive standard of care synkinesis treatment. Depending on the treatment arm, they will receive additional botox injections to temporalis and masseter muscle groups which will only be injected on the ipsilateral side to the facial nerve injury. Decision to include the temporalis and/or masseter muscles will be based on each patients response to screening questions regarding jaw pain/tightness or headaches. | Drug | Even MRN, Odd MRN |
Primary outcome
Synkinesis Assessment Questionnaire (SAQ)
Time frame: Pre-treatment and repeated 5 weeks post-treatment
This 9-item questionnaire assesses functional status (hyperactive and/or inappropriately active facial muscles) related to facial synkinesis and is already given at each clinic visit as a routine part of clinical practice. The survey is well validated for evaluating synkinesis symptoms in patients with facial nerve injury. SAQ scale: 1 = seldom or not at all, 2 = occasionally, or very mildly, 3 = sometimes, or mildly, 4 = most of the time, or moderately, 5 = all the time, or severely
Headache Impact Test (HIT-6)
Time frame: Pre-treatment and repeated 5 weeks post-treatment
This 6-item questionnaire seeks to understand the severity of headaches and impact on every-day quality of life. The survey is widely validated for assessing headache symptom and burden. We plan to add in 3 additional questions to this survey including 1) how often do you experience headaches (1 = never or rarely, 2 = 1-2 days a week, 3 = 3-4 days a week, 4 = nearly every day), 2) on a scale of 1-10 (10 = most severe) how severe are your headaches, and 3) I feel as if my Botox injections improved my headaches (Y/N). HIT-6 Scale: 1 = Never 2 = Rarely 3 = Sometimes 4 = Very often 5 = Always
Temporomandibular Disorder Questionnare (TMD-7)
Time frame: Pre-treatment and repeated 5 weeks post-treatment
This 7-item questionnaire assesses symptoms related to temporomandibular mandibular joint (TMJ) disorder. It asks about jaw pain, tightness, clicking and difficulty eating, among other things. We plan to add in 3 additional questions to this survey including 1) how often do you experience jaw pain/tightness (1 = never or rarely, 2 = 1-2 days a week, 3 = 3-4 days a week, 4 = nearly every day), 2) on a scale of 1-10 (10 = most severe) how severe is your jaw pain/tightness, and 3) I feel as if my Botox injections improved my jaw pain/tightness (Y/N). TMD-7 Scale: 1 = Rarely or Never 2 = A few times a month 3 = Once or Twice a Week 4 = Nearly Every Day
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Individual participant dataSharing planned: No
Related trials for Synkinesis
Not yet recruiting
Mindfulness in Nonflaccid Facial Paralysis
Facial Paralysis
Enrolling by invitationObservational study
Turkish Validation of the Synkinesis Assessment Questionnaire (SAQ)
Facial Paralysis, Facial Palsy
Recruiting
Evaluation of the Effectiveness of Virtual Reality Self-rehabilitation in the Treatment of Facial Paralysis and Synkinesis
Peripheral Facial Palsy, Rehabilitation
RecruitingObservational study
Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies
Congenital Fibrosis of Extraocular Muscles, Duane Retraction Syndrome
Enrolling by invitation
Motor Imagery and Mirror Therapy on Synkinesis, Facial Asymmetry, Facial Function and QoF in Bell's Palsy Patients.
Bell Palsy
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.
Priyesh Patel, MD principal investigator
VUMC
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Botulinum Toxin Type A Injection [Botox] in people with Synkinesis, run by Vanderbilt University Medical Center.
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 6 inclusion and 2 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: withdrawn, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Synkinesis Assessment Questionnaire (SAQ) (time frame: Pre-treatment and repeated 5 weeks post-treatment). The study lists 3 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 3 Nov 2026.