SmilingPhase 1/2NCT05127018
Higher Doses of Botulinum Toxin in the Treatment of Gummy Smile
A Phase 1/2 study testing injection of Botulinum type A in people with Smiling and Botulinum Toxins, Type A, run by Peking University at 1 site in China.
Trial summary
Botulinum type A (BTX-A) is an easy and efficacious treatment for gingival smile (GS). However, the necessary for higher-doses among patients are controversial. The objective was to compare the reduction of gingival exposure using two methods in patients with different dosage. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Smiling, Botulinum Toxins, Type A
- What is being tested?
- injection of Botulinum type A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteChina
- Study dates
- 20 Nov 2019to 20 Oct 2021
- Phase
- Phase 1/2
- 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 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- ≥ 3.0-mm anterior gingival exposure upon unrestricted, "full-blown" smiling
- healthy adults
Who cannot join
- contraindication of BTX-A
- previous diseases or treatments affecting the position of the gingiva or upper lips
- history of BTX-A injections to the head or neck region
- facial paralysis
- having received and/or receiving active orthodontic treatment that includes vertical dimension treatment, such as extrusion and intrusion, and presence of
- periodontal disease
- subject's refusal to participate
Trial locations and contacts
1 site in 1 country.
China1 site
Peking University School and Hospital of Stomatology
Beijing, Beijing Municipality, 100010
About this study
Official title: Dose Higher Doses of Botulinum Toxin Show Better Intensity and Duration in the Treatment of Gummy Smile
Botulinum type A (BTX-A) is an easy and efficacious treatment for gingival smile (GS). However, the necessary for higher-doses among patients are controversial. The objective was to compare the reduction of gingival exposure using two methods in patients with different dosage. In this prospective self-controlled study, healthy GS participates who had an anterior gingival exposure (GE) of more than 3 mm were enrolled and administered with 2-5 U BTX-A (total, 4-10 U) injections into 1-2 points according to the severity presented pretreatment in the Average-dose Method. And after 8 months, the Higher-doses Method was administered the same point injection of 3-10 U BTX-A (total, 6-20 U). Data were collected at baseline and 4, 12, 32 and 60 weeks of follow-up.
Read the detailed description
The smile is one of the universal facial expressions of humans. Gingival smile is characterized by gingival exposure of >3 mm upon smiling. The degree of gingival exposure can vary substantially between patients, with patients presenting gingival exposure of up to more than 10 mm. The prevalence of gingival smile is 10.57%, and it is more frequently observed in females. Although gingival smile is merely an anatomical variation, it can be considered unattractive, causing significant distress and impacting one's quality of life. Moreover, most orthodontists and dentists regard gingival smile as an important risk factor for dental treatment.
Gingival smile involves a complex interaction between the facial muscles, bone, and skin; specifically, it is related to hypermobility of the upper lip with muscle involvement and alterations in anatomical features, such as a short clinical dental crown, anterior dentoalveolar extrusion, maxillary excess, and a short upper lip. Therapies for gingival smile range from botulinum toxin injections to surgical interventions according to its etiology. Although the outcomes of surgical procedures are long-lasting, botulinum toxin type A treatment is an easy and fast outpatient procedure that requires no downtime and has high efficacy rates. Nevertheless, there are controversies around the optimal dose and injection site of botulinum toxin type A. Moreover, the efficiency of botulinum toxin type A for gingival smile varies markedly between studies, with the improvement rate of gingival exposure ranging from 62.06% to 98%. Sucupira and Abramovitz advocate the use of a low amount of botulinum toxin type A of 1.95 U per side for the treatment of gingival smile. They noted an average satisfaction level of 9.75 on a 10-point scale with this approach. They claimed that higher doses does not provide further benefit, and, in fact, could lead to lip ptosis, asymmetry, and excessive upper lip length. However, Polo disagreed with their argument, claiming 2-5 U injection of botulinum toxin type A according to the severity of gingival smile. In this regard, Garcia and Fulton showed that low-dose injection of botulinum toxin per muscle (2-5 IU) was as effective as higher doses. Though prior studies have demonstrated a correlation between higher doses of botulinum toxin and intensity and duration of muscle paralyses, no conclusion can be drawn regarding duration and intensity of doses used in the recent studies. A safe approach advocated by some authors consists of starting with low toxin doses initially, with retouching at a later stage if required. In this study, the investigators compared botulinum toxin type A efficiency using the average-dose method (2-5 U botulinum toxin type A per side determined according to the severity of anterior gingival smile) and , the higher-dose method (3-10 U botulinum toxin type A per side determined according to the severity of anterior gingival smile). The investigators aimed to assess the efficiency and duration of these approaches, as well as side effects and patients' satisfaction with treatment.
- Conditions
- Smiling, Botulinum Toxins, Type A
- Being tested
- injection of Botulinum type A
- Keywords
- gummy smile, botulinum toxin, dose
- Medical subject headings
- Smiling
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
injection of Botulinum type ADrug
Also called injection of Botulinum type A(Botox, Allergan, Irvine, CA)
The participates were allocated to two different application methods: Simplified Method for the first injection and Individualized Method 8 months later. All the patients underwent twice injection with each methods with no change of the BTX-A(Botox, Allergan, Irvine, CA) and other injection details: Lyophilized 100 U of Botox was reconstituted in 2.5 mL of 0.9% sodium chloride solution. The injections were made with a 27-gauge insulin syringe. The treatment was an outpatient procedure and all injections were performed by one of the authors (X.G.). No anesthesia was given during the procedure.
| Study group | Role | What they receive |
|---|---|---|
| the average-dose method | Active comparator | With the average-dose method, the dose was individualized according to the severity of anterior gingival exposure pretreatment. For mild gingival smile (3-5 mm), a single-site injection of 2 U botulinum toxin type A [total, 4 U] at both the right and left levator labii superioris alaeque nasi muscles) was administered. For moderate (5-7 mm) and severe (≥7 mm) gingival smile, 3 U and 5 U of botulinum toxin type A, respectively, were injected per side (total, 6 U and 10U, respectively). The injection points were located at bilateral levator labii superioris alaeque nasi muscles and at the Yonsei point26, with half doses administered at each point. Receives: Drug: injection of Botulinum type A |
| the higher-dose method | Experimental | With this method, patients were administered botulinum toxin type A after 8 months when the effect of the previous injection had vanished. The injection dose (U) per side was set as the absolute value of the preoperative anterior gingival exposure (mm). For example, if the preoperative anterior gingival exposure was 5mm, then the patient would be injected with 5 U of botulinum toxin per side (total, 10U). The injection points were located at bilateral levator labii superioris alaeque nasi muscles and at the Yonsei point26, with half doses administered at each point. Receives: Drug: injection of Botulinum type A |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anterior Gingival Exposure (GE) 4 Weeks Post-injection
The distance from the superior margin point of the right incisor to the lower margin of the upper lip upon maximum smile.
Measured: 4 weeks postinjection
Secondary outcomes (3)
Anterior Gingival Exposure (GE) 12 Weeks Post-injection
The distance from the superior margin point of the right incisor to the lower margin of the upper lip upon maximum smile.
Measured: 12 weeks postinjection
Anterior Gingival Exposure (GE) 24 Weeks Post-injection
The distance from the superior margin point of the right incisor to the lower margin of the upper lip upon maximum smile.
Measured: 24 weeks postinjection
Anterior Gingival Exposure (GE) 48 Weeks Post-injection
The distance from the superior margin point of the right incisor to the lower margin of the upper lip upon maximum smile.
Measured: 48 weeks postinjection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2021
- Study start20 Nov 2019
- Primary completion20 Aug 2020
- Study completion20 Oct 2021
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 SmilingStudies of the same condition, open and under way.
- More trials run by Peking UniversityThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Peking University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gong Xi, DDS, Peking University
- Investigators
- Xi Gong, Principal investigator, Peking University School of Stomatology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05127018
- Sponsor's protocol ID
- pkusshighdose
- Status last verified
- Apr 2023
- First submitted
- 9 Nov 2021
- Last updated
- 26 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Higher Doses of Botulinum Toxin Show Better Intensity and Duration in the Treatment of Gummy Smile
- ClinicalTrials.gov ID
- NCT05127018
- Acronym / sponsor ID
- pkusshighdose
- Conditions
- Smiling, Botulinum Toxins, Type A
- Keywords
- gummy smile, botulinum toxin, dose
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Peking UniversityUniversity, hospital or other
- Study start
- 20 Nov 2019 (actual)
- Primary completion
- 20 Aug 2020 (actual)
- Study completion
- 20 Oct 2021 (actual)
- First posted
- 19 Nov 2021 (actual)
- Results
- Posted 26 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Botulinum type A (BTX-A) is an easy and efficacious treatment for gingival smile (GS). However, the necessary for higher-doses among patients are controversial. The objective was to compare the reduction of gingival exposure using two methods in patients with different dosage. In this prospective self-controlled study, healthy GS participates who had an anterior gingival exposure (GE) of more than 3 mm were enrolled and administered with 2-5 U BTX-A (total, 4-10 U) injections into 1-2 points according to the severity presented pretreatment in the Average-dose Method. And after 8 months, the Higher-doses Method was administered the same point injection of 3-10 U BTX-A (total, 6-20 U). Data were collected at baseline and 4, 12, 32 and 60 weeks of follow-up.
Detailed description
The smile is one of the universal facial expressions of humans. Gingival smile is characterized by gingival exposure of >3 mm upon smiling. The degree of gingival exposure can vary substantially between patients, with patients presenting gingival exposure of up to more than 10 mm. The prevalence of gingival smile is 10.57%, and it is more frequently observed in females. Although gingival smile is merely an anatomical variation, it can be considered unattractive, causing significant distress and impacting one's quality of life. Moreover, most orthodontists and dentists regard gingival smile as an important risk factor for dental treatment.
Gingival smile involves a complex interaction between the facial muscles, bone, and skin; specifically, it is related to hypermobility of the upper lip with muscle involvement and alterations in anatomical features, such as a short clinical dental crown, anterior dentoalveolar extrusion, maxillary excess, and a short upper lip. Therapies for gingival smile range from botulinum toxin injections to surgical interventions according to its etiology. Although the outcomes of surgical procedures are long-lasting, botulinum toxin type A treatment is an easy and fast outpatient procedure that requires no downtime and has high efficacy rates. Nevertheless, there are controversies around the optimal dose and injection site of botulinum toxin type A. Moreover, the efficiency of botulinum toxin type A for gingival smile varies markedly between studies, with the improvement rate of gingival exposure ranging from 62.06% to 98%. Sucupira and Abramovitz advocate the use of a low amount of botulinum toxin type A of 1.95 U per side for the treatment of gingival smile. They noted an average satisfaction level of 9.75 on a 10-point scale with this approach. They claimed that higher doses does not provide further benefit, and, in fact, could lead to lip ptosis, asymmetry, and excessive upper lip length. However, Polo disagreed with their argument, claiming 2-5 U injection of botulinum toxin type A according to the severity of gingival smile. In this regard, Garcia and Fulton showed that low-dose injection of botulinum toxin per muscle (2-5 IU) was as effective as higher doses. Though prior studies have demonstrated a correlation between higher doses of botulinum toxin and intensity and duration of muscle paralyses, no conclusion can be drawn regarding duration and intensity of doses used in the recent studies. A safe approach advocated by some authors consists of starting with low toxin doses initially, with retouching at a later stage if required. In this study, the investigators compared botulinum toxin type A efficiency using the average-dose method (2-5 U botulinum toxin type A per side determined according to the severity of anterior gingival smile) and , the higher-dose method (3-10 U botulinum toxin type A per side determined according to the severity of anterior gingival smile). The investigators aimed to assess the efficiency and duration of these approaches, as well as side effects and patients' satisfaction with treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| the average-dose method | Active comparator | Drug: injection of Botulinum type AWith the average-dose method, the dose was individualized according to the severity of anterior gingival exposure pretreatment. For mild gingival smile (3-5 mm), a single-site injection of 2 U botulinum toxin type A [total, 4 U] at both the right and left levator labii superioris alaeque nasi muscles) was administered. For moderate (5-7 mm) and severe (≥7 mm) gingival smile, 3 U and 5 U of botulinum toxin type A, respectively, were injected per side (total, 6 U and 10U, respectively). The injection points were located at bilateral levator labii superioris alaeque nasi muscles and at the Yonsei point26, with half doses administered at each point. |
| the higher-dose method | Experimental | Drug: injection of Botulinum type AWith this method, patients were administered botulinum toxin type A after 8 months when the effect of the previous injection had vanished. The injection dose (U) per side was set as the absolute value of the preoperative anterior gingival exposure (mm). For example, if the preoperative anterior gingival exposure was 5mm, then the patient would be injected with 5 U of botulinum toxin per side (total, 10U). The injection points were located at bilateral levator labii superioris alaeque nasi muscles and at the Yonsei point26, with half doses administered at each point. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- ≥ 3.0-mm anterior gingival exposure upon unrestricted, "full-blown" smiling
- healthy adults
Key exclusion criteria (7 listed)
- contraindication of BTX-A
- previous diseases or treatments affecting the position of the gingiva or upper lips
- history of BTX-A injections to the head or neck region
- facial paralysis
- having received and/or receiving active orthodontic treatment that includes vertical dimension treatment, such as extrusion and intrusion, and presence of
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 |
|---|---|---|
| injection of Botulinum type AAlso: injection of Botulinum type A(Botox, Allergan, Irvine, CA)The participates were allocated to two different application methods: Simplified Method for the first injection and Individualized Method 8 months later. All the patients underwent twice injection with each methods with no change of the BTX-A(Botox, Allergan, Irvine, CA) and other injection details: Lyophilized 100 U of Botox was reconstituted in 2.5 mL of 0.9% sodium chloride solution. The injections were made with a 27-gauge insulin syringe. The treatment was an outpatient procedure and all injections were performed by one of the authors (X.G.). No anesthesia was given during the procedure. | Drug | the average-dose method, the higher-dose method |
Primary outcome
Anterior Gingival Exposure (GE) 4 Weeks Post-injection
Time frame: 4 weeks postinjection
The distance from the superior margin point of the right incisor to the lower margin of the upper lip upon maximum smile.
3 secondary outcomes
Anterior Gingival Exposure (GE) 12 Weeks Post-injection
Time frame: 12 weeks postinjection
Anterior Gingival Exposure (GE) 24 Weeks Post-injection
Time frame: 24 weeks postinjection
Anterior Gingival Exposure (GE) 48 Weeks Post-injection
Time frame: 48 weeks postinjection
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Xi Gong principal investigator
Peking University School of Stomatology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing injection of Botulinum type A in people with Smiling and Botulinum Toxins, Type A, run by Peking University at 1 site in China.
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 7 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 26 Apr 2023. 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 China. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 26 Apr 2023). 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?
Anterior Gingival Exposure (GE) 4 Weeks Post-injection (time frame: 4 weeks postinjection). 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 26 Apr 2023.