Botulinum Toxin to Improve Results in Cleft Lip Repair

Sponsor

Chang Gung Memorial Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT01429402

Collaborator

(none)

120

Enrollment

Location

Arms

157

Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Botulinum toxin type A (Botox; Allergan, Inc., Irvine, Calif) is widely used for facial rejuvenation and many other medical indications. It induces chemodenervation through its action on the presynaptic neuron, preventing release of acetylcholine, which leads to functional denervation of striated muscle for 2 to 6 months after injection. The use of botulinum toxin injection to reduce the facial scar is logical because this could reduce the tensile distracting force of the upper lip caused by the orbicularis oris muscle pull. Tollefson has demonstrate that botulinum toxin injection has decrease lip tension after primary lip repair in 3 children at 3-6 months of age The main aim of this randomized trial is to compare whether post-operative peri-surgical-injection of botulinum toxin into bilateral orbicularis oris muscles can improve scar formation for both primary and secondary cleft lip surgery.

Condition or Disease	Intervention/Treatment	Phase
Scar	Drug: Botulinum Toxin Type A Drug: Botulinum Type A Drug: Normal Saline Drug: Normal Saline	Phase 3

Detailed Description

This is a randomized controlled trial primarily designed to compare the scarring after primary and secondary cleft lip repair using post-operative botulinum toxin injection. There will be 4 main groups in this study:-

Study group I: For primary lip surgery, immediately after primary lip repair will received botulinum toxin injection (1-2U/kg, at 25U/mL) into the bilateral aberrant oriented orbicularis ocuris muscle via 4 superficial injection site (Tollefson TT 2006).
Study group II: For revision lip surgery, immediately after revision lip surgery 3 injection of 2.5U of botulinum toxin with a distance of 0.5 cm from each injection and operative wound are injected over both sides of upper lip in a adult on the operation room.
Control group I : Similar amount (in C.C.) of normal saline will be injected after primary lip surgery at 3 months of age.
Control group II: Similar amount (in C.C.) of normal saline will be injected after revision lip surgery (secondary cleft lip repair).
ELIGIBILITY 4.1 Inclusion criteria for the primary lip repair group (i) Baby born with cleft lip who will receive primary lip repair at 3 months of age (iii) Written informed consent given by parent/guardian.

4.2 Inclusion criteria for the secondary lip repair group (i) Adult > 16 years old. (ii) Moderate to severe secondary cleft lip and/or nose deformity that warrants corrective surgery.

(iii) Written informed consent given by parent/guardian/patient.

4.3 Patient numbers: 60 for primary lip repair and 60 for secondary lip repair

4.31 Sample size calculation: 10 consecutive patient selected from our OPD on march 2009. Vancouver Scar Scale means 4.6 with SD 1.264911 (rage 3-7). If the study group with improvement of 1 is clinical significant, giving power 0.8 with the same SD, the sample size calculated will be 26.

Using Terason Ultrasound (capacity of measured 1/100 cm or 1/10 mm) the scar width mean is 1.13 mm with SD .6201254. If the study group with improvement of 0.5 mm as clinical significant, giving the power of 0.8 with the same SD, the sample size calculated will be 25.

We will use 30 patients for each group.

4.41 Exclusion criteria for primary lip repair

Combined other craniofacial anomalies
Without permission of parent/guardian, without signed informed consent by parent/guardian.

4.42 Exclusion criteria for the secondary lip repair

Less than 15 years old
Mild secondary cleft lip and / or nose deformity that does not warrant corrective surgery.
Without written informed consent.
Without permission of parent/guardian, the patient signed the consent himself.
Botulinum Toxin injection 5.1 For Study group I: Injections are placed into the orbicularis oris muscle 5 mm adjacent to the scar and the vermilion border on each side of the operative wound (A total of 3 injections per side making a total of 6 injections per patient). 1-2U/kg (total dosage for baby) and 2.5 U (adult ) of botulinum toxin (Botox; allergen, Inc., Irvine, Calif) will be used for each injection. A total dosage of 15 U (for adult) will be injected into each patient.

For control group a similar amount of Normal saline will be injected.

STUDY VISITS AND ASSESSMENTS 6.1 Registration and Randomization (i) Confirmation of eligibility (ii) Information Sheet (iii) Written informed consent (iv) Registration of baby and adult into study and randomization (v) Scheduling of patient for botox injection immediately after surgery.

6.2 Follow-up Assessments 6.2.1 Vancouver scar scale (Sullivan T 1990) measures pigmentation, vascularity, pliability and scar height on the postoperative 6 month F/U.

Ultrasonography measurement of the scar (Fong SS 1997)

For both primary and secondary lip surgery, the patient will receive postoperative follow up during 1wk, 1mo, 3mo, 6mo. On the 1st week postoperative follow up, the stitches will be removed, 3M taping will be placed over the wound to reduce surface tension and minimize the scar formation. On the 6th mo follow up, a lay person will assess the scar using the Vancouver scar and a plastic surgeon will use ultrasonography to measure the scar.

The Independent T-Student test will be used to analyze the statistical significance between the two groups.

Photographic measurement of scar The scar width of the patient's picture at 6 month after surgery will be measured using photoshop CS3 extended. One ruler will be placed on the patient's lip before taken the photo. Then the scar width could be measured.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Botulinum Toxin to Improve Results in Cleft Lip Repair

Study Start Date :

Jul 1, 2000

Actual Primary Completion Date :

Aug 1, 2010

Anticipated Study Completion Date :

Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: study group I For primary lip surgery, immediately after primary lip repair will received botulinum toxin injection (1-2U/kg, at 25U/mL) into the bilateral aberrant oriented orbicularis ocuris muscle via 4 superficial injection site	Drug: Botulinum Toxin Type A 1-2U/kg, at 25U/mL, into the bilateral aberrant oriented orbicularis ocuris muscle via 4 superficial injection site; only once after surgery. No additional injection is needed Other Names: Botox ( Allergan, Inc., Irvine, Calif)
Experimental: Study Group II For revision lip surgery, immediately after revision lip surgery 3 injection of 2.5U of botulinum toxin with a distance of 0.5 cm from each injection and operative wound are injected over both sides of upper lip in a adult on the operation room.	Drug: Botulinum Type A b. Study group II: For revision lip surgery, immediately after revision lip surgery 3 injection of 2.5U of botulinum toxin with a distance of 0.5 cm from each injection and operative wound are injected over both sides of upper lip in a adult on the operation room just after surgery. (total dosage injected 15U) Other Names: Botox ( Allergan, Inc., Irvine, Calif)
Placebo Comparator: Control Group I Similar amount as group I (in C.C.) of normal saline will be injected after primary lip surgery at 3 months of age.	Drug: Normal Saline Similar amount (in C.C.) of normal saline as group I will be injected after primary lip surgery at 3 months of age. Other Names: NaCl 0.9%
Placebo Comparator: Control II Similar amount (in C.C.) as Study Group II of normal saline will be injected after revision lip surgery (secondary cleft lip repair).	Drug: Normal Saline Similar amount (in C.C.) of normal saline as study group II will be injected after revision lip surgery (secondary cleft lip repair). Other Names: NaCl 0.9%

Outcome Measures

Primary Outcome Measures

Vancouver Scar scale [6 month]
Vancouver scar scale measures pigmentation, vascularity, pliability and scar height on the postoperative 6 month F/U.

Secondary Outcome Measures

Ultrasonography scar measurement [6 month]
On the 6th mo follow up, ultrasonography to measure the scar width will be performed.
Photographic measurement [6 month]
The scar width of the patient's picture at 6 month after surgery will be measured using photoshop CS3 extended. One ruler will be placed on the patient's lip before taken the photo. Then the scar width could be measured.

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Months to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Inclusion criteria for the primary lip repair group

Baby born with cleft lip who will receive primary lip repair at 3 months of age
Written informed consent given by parent/guardian.

Inclusion criteria for the secondary lip repair group

Adult > 16 years old.
Moderate to severe secondary cleft lip and/or nose deformity that warrants corrective surgery.
Written informed consent given by parent/guardian/patient.

Exclusion Criteria:

Those patient not fit inclusion criteria

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chun Shin Chang	Taoyuan		Taiwan	333

Sponsors and Collaborators

Chang Gung Memorial Hospital

Investigators

Principal Investigator: Chun-Shin Chang, M.D., Chang Gung Memorial Hospital
Principal Investigator: Philip Kuo-Ting Chen, M.D., Chang Gung Memorial Hospital