Trial Outcomes & Findings for Higher Doses of Botulinum Toxin in the Treatment of Gummy Smile (NCT NCT05127018)

NCT ID: NCT05127018

Last Updated: 2023-04-26

Results Overview

The distance from the superior margin point of the right incisor to the lower margin of the upper lip upon maximum smile.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 33 participants
• Primary outcome timeframe: 4 weeks postinjection
• Results posted on: 2023-04-26

Participant Flow

According to the estimated sample size, 33 participants need to be included in the study, and 33 people were actually included, but this study was a prospective, self-controlled clinical study, which is two treatments for the same group of patients, so the total sample size is 33 people.

Participant milestones

Measure	The Treatment Group In this prospective self-controlled study, healthy participants with gummy smile underwent two treatment methods. First, participants were injected with the average-dose, which 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 point, with half doses administered at each point. And 8 months later All the patients underwent second injection of the higher-dose method. 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 point, with half doses administered at each point.
the Average-dose Period STARTED	33
the Average-dose Period COMPLETED	33
the Average-dose Period NOT COMPLETED	0
the Higher-dose Method Period STARTED	33
the Higher-dose Method Period COMPLETED	33
the Higher-dose Method Period NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	The Treatment Group n=33 Participants In this prospective self-controlled study, healthy participants with gummy smile underwent two treatment methods. First, participants were injected with the average-dose, which 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 point, with half doses administered at each point. And 8 months later All the patients underwent second injection of the higher-dose method. 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 point, with half doses administered at each point.
Age, Categorical <=18 years	0 Participants n=33 Participants
Age, Categorical Between 18 and 65 years	33 Participants n=33 Participants
Age, Categorical >=65 years	0 Participants n=33 Participants
Age, Continuous	31.1 years STANDARD_DEVIATION 6.6 • n=33 Participants
Sex: Female, Male Female	31 Participants n=33 Participants
Sex: Female, Male Male	2 Participants n=33 Participants
Region of Enrollment China	33 participants n=33 Participants
anterior gingival exposure	6.4 mm STANDARD_DEVIATION 1.5 • n=33 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	the First Injection(the Average-dose Method) n=33 Participants 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. injection of Botulinum type A: 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.	the Second Injection(the Higher-dose Method) n=33 Participants 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. injection of Botulinum type A: 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.
Anterior Gingival Exposure (GE) 4 Weeks Post-injection	3.6 mm Standard Deviation 1.5	3.0 mm Standard Deviation 1.5

SECONDARY outcome

Timeframe: 12 weeks postinjection

The distance from the superior margin point of the right incisor to the lower margin of the upper lip upon maximum smile.

Outcome measures

Measure	the First Injection(the Average-dose Method) n=33 Participants 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. injection of Botulinum type A: 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.	the Second Injection(the Higher-dose Method) n=33 Participants 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. injection of Botulinum type A: 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.
Anterior Gingival Exposure (GE) 12 Weeks Post-injection	5.4 mm Standard Deviation 1.6	4.9 mm Standard Deviation 1.5

SECONDARY outcome

Timeframe: 24 weeks postinjection

The distance from the superior margin point of the right incisor to the lower margin of the upper lip upon maximum smile.

Outcome measures

Measure	the First Injection(the Average-dose Method) n=33 Participants 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. injection of Botulinum type A: 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.	the Second Injection(the Higher-dose Method) n=33 Participants 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. injection of Botulinum type A: 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.
Anterior Gingival Exposure (GE) 24 Weeks Post-injection	6.3 mm Standard Deviation 1.4	5.8 mm Standard Deviation 1.2

SECONDARY outcome

Timeframe: 48 weeks postinjection

The distance from the superior margin point of the right incisor to the lower margin of the upper lip upon maximum smile.

Outcome measures

Measure	the First Injection(the Average-dose Method) n=33 Participants 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. injection of Botulinum type A: 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.	the Second Injection(the Higher-dose Method) n=33 Participants 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. injection of Botulinum type A: 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.
Anterior Gingival Exposure (GE) 48 Weeks Post-injection	7.0 mm Standard Deviation 1.4	6.5 mm Standard Deviation 1.0

Adverse Events

the First Injection（the Average-dose Method）

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

the Second Injection（the Higher-dose Method）

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	the First Injection（the Average-dose Method） n=33 participants at risk 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. injection of Botulinum type A: 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.	the Second Injection（the Higher-dose Method） n=33 participants at risk 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. injection of Botulinum type A: 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.
Skin and subcutaneous tissue disorders Slight lip ptosis	15.2% 5/33 • Number of events 5 • For follow-up of the first injection, the participants was followed up at 4, 12 weeks and 48 weeks. For the re-injection, the participants was followed up at 4, 12, 48 weeks. The intervention in this study is low-dose injection of botulinum toxin (6U/person), which is very safe, with no participants at risk for Serious Adverse Events or for All-Cause Mortality.	12.1% 4/33 • Number of events 4 • For follow-up of the first injection, the participants was followed up at 4, 12 weeks and 48 weeks. For the re-injection, the participants was followed up at 4, 12, 48 weeks. The intervention in this study is low-dose injection of botulinum toxin (6U/person), which is very safe, with no participants at risk for Serious Adverse Events or for All-Cause Mortality.

Additional Information

Xi Gong

Peking University School of Stomatology

Phone: 15201304426

Email: gongx31480528@163.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place