Botulinum Toxin A Single Blind Split-Face Randomized Pilot Study

• Sponsor: ICLS Dermatology & Plastic Surgery (Other)
• Overall Status: Completed
• CT.gov ID: NCT02907268
• Collaborator: (none)
• Enrollment: 10
• Arms: 2
• Duration (Months): 4

Study Details

Study Description

Brief Summary

A 16-week single-blind, split-face, randomized study. Each patient served as their own control, receiving onabotulinumtoxinA and abobotulinumtoxinA randomized to either the left or right side of the face. Patients received intradermal BTXA injections at week 0 and intramuscular BTXA injections at week 2. The objective is to examine the effectiveness of intradermal botulinum toxin type A (BTXA) injection in improving skin texture and midface lift while reducing pore size and sebum production, as well as investigate the differences in effectiveness between onabotulinumtoxinA and abobotulinumtoxinA using intradermal and intramuscular injection methods.

Condition or Disease	Intervention/Treatment	Phase
Facial Rhytids	Drug: onabotulinumtoxinA; Drug: abobotulinumtoxinA	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Single Blind, Split-Face, Randomized, Pilot Study Comparing the Effects of Intradermal and Intramuscular Injection of Two Commercially Available Botulinum Toxin A Formulas to Reduce Signs of Facial Aging
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Treatment Arm A The first treatment group received onabotulinumtoxinA (Botox) on the right side of their face and abobotulinumtoxinA (Dysport) on the left side of their face. Baseline treatment at Week 0 included the intradermal injection of onabotulinumtoxinA on one side of the face and abobotulinumtoxinA on the other. Patients were treated at Week 2 with traditional intramuscular injections consisting of onabotulinumtoxinA on the same side of their face as at Week 0 and abobotulinumtoxinA on the other side. Patients were treated based on individual need, and thus the treatment volumes were not controlled or standardized.	Drug: onabotulinumtoxinA; OnabotulinumtoxinA (Botox; Allergan) was approved by the FDA in 2002. Intervention administered by study nurse. Intradermal administered in a regular 1 cm2 grid across the cheeks and forehead. Intramuscular administered as per normal practice.; Other Names: Botox ; Drug: abobotulinumtoxinA; AbobotulinumtoxinA (Dysport; Galderma) was approved by the FDA in 2009. Intervention administered by study nurse. Intradermal administered in a regular 1 cm2 grid across the cheeks and forehead. Intramuscular administered as per normal practice.; Other Names: Dysport
Active Comparator: Treatment Arm B The second treatment group received abobotulinumtoxinA (Dysport) on the right side of their face and onabotulinumtoxinA (Botox) on the left side of their face. Baseline treatment at Week 0 included the intradermal injection of onabotulinumtoxinA on one side of the face and abobotulinumtoxinA on the other. Patients were treated at Week 2 with traditional intramuscular injections consisting of onabotulinumtoxinA on the same side of their face as at Week 0 and abobotulinumtoxinA on the other side. Patients were treated based on individual need, and thus the treatment volumes were not controlled or standardized.	Drug: onabotulinumtoxinA; OnabotulinumtoxinA (Botox; Allergan) was approved by the FDA in 2002. Intervention administered by study nurse. Intradermal administered in a regular 1 cm2 grid across the cheeks and forehead. Intramuscular administered as per normal practice.; Other Names: Botox ; Drug: abobotulinumtoxinA; AbobotulinumtoxinA (Dysport; Galderma) was approved by the FDA in 2009. Intervention administered by study nurse. Intradermal administered in a regular 1 cm2 grid across the cheeks and forehead. Intramuscular administered as per normal practice.; Other Names: Dysport

Outcome Measures

Primary Outcome Measures

1. Blinded Assessment: Overall Change in Facial Wrinkles From Baseline to Week 2 as Assessed by a Numeric Rating Scale Based on Pre- and Post-treatment Photographs [Baseline and 2 weeks]

   Blinded assessments of overall change in facial wrinkles from baseline to week 2 based on pre and post treatment photographs. Measured on a 5 point scale which is a static assessment of wrinkle severity. 0=wrinkles absent (minimum), 1=shallow but visible wrinkles, 2=fine lines slight indentation, 3=clear indentation 0-1mm deep, 4=moderate indentation 1-2mm deep, 5=deep indentation >2mm deep (maximum). A higher value = a worse outcome (more severe wrinkles). Includes 9 subscales measured on the same scale described above. Subscales measure wrinkle severity in the left and right forehead region, left and right cheek region, left and right crow's feet region, left and right upper lip region, and glabellar region. All scores were computed by averaging subscale ratings.

2. Blinded Assessment: Overall Change in Facial Wrinkles From Baseline to Week 4 as Assessed by a Numeric Rating Scale Based on Pre- and Post-treatment Photographs [Baseline and 4 weeks]

   Blinded assessments of overall change in facial wrinkles from baseline to week 4 based on pre and post treatment photographs. Measured on a 5 point scale which is a static assessment of wrinkle severity. 0=wrinkles absent (minimum), 1=shallow but visible wrinkles, 2=fine lines slight indentation, 3=clear indentation 0-1mm deep, 4=moderate indentation 1-2mm deep, 5=deep indentation >2mm deep (maximum). A higher value = a worse outcome (more severe wrinkles). Includes 9 subscales measured on the same scale described above. Subscales measure wrinkle severity in the left and right forehead region, left and right cheek region, left and right crow's feet region, left and right upper lip region, and glabellar region. All scores were computed by averaging subscale ratings.

3. Blinded Assessment: Overall Change in Facial Wrinkles From Baseline to Week 16 as Assessed by a Numeric Rating Scale Based on Pre- and Post-treatment Photographs [Baseline and 16 weeks]

   Blinded assessments of overall change in facial wrinkles from baseline to week 16 based on pre and post treatment photographs. Measured on a 5 point scale which is a static assessment of wrinkle severity. 0=wrinkles absent (minimum), 1=shallow but visible wrinkles, 2=fine lines slight indentation, 3=clear indentation 0-1mm deep, 4=moderate indentation 1-2mm deep, 5=deep indentation >2mm deep (maximum). A higher value = a worse outcome (more severe wrinkles). Includes 9 subscales measured on the same scale described above. Subscales measure wrinkle severity in the left and right forehead region, left and right cheek region, left and right crow's feet region, left and right upper lip region, and glabellar region. All scores were computed by averaging subscale ratings.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Female subjects between ages of 35 to 65 years (inclusive) who exhibit static wrinkles in the following areas: glabella (forehead frowns), periorbital area (crows feet). Static wrinkles in additional areas of the face are also acceptable.

• Subject is willing to maintain the same skin care regimen throughout the study and has already maintained this skin care regime for 4 weeks prior to baseline.

• The subject is able to comply with study procedures and instructions and is committed to attend all study visits within the given timelines.

• Subject is judged to be a good candidate by study nurse upon identification of dynamic and/or static wrinkles in the areas of movement, and with a moderate amount of skin laxity.

• Subject is willing to use contraception

• A signed informed consent form by a subject able to give consent, prior to any study procedures are performed.

Exclusion Criteria:

• Sensitivity and/or contraindications to botulinum toxin A other ingredients contained in the botulinum toxin A products.

• Any medical condition, in the opinion of the investigator, that would interfere with safety or any study procedures (e.g. auto-immune disease, history of severe allergies, hypertrophic scars, immunotherapeutic treatment, inflammatory or infectious complaints at injection sites, unable to give consent)

• Treatment with botulinum toxin A injections in the neck or face within 1 year of baseline treatment

• Treatment with facial fillers less than 1 year prior to baseline

• Females of childbearing potential who are pregnant, breastfeeding or plan to get pregnant during the course of the study.

• Previous treatment with Lasers, Ultrasound Technology or Radio Frequency on the face and/or neck within 1 year prior to baseline.

• Treatment with Accutane (isotretinoin) or other oral medications for acne during 1 year prior to baseline.

• The use of anti-aging products containing retinol

• Known allergy to cow's milk protein

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• ICLS Dermatology & Plastic Surgery

Investigators

• Principal Investigator: Sheetal Sapra, MD, FRCPC, ICLS Dermatology & Plastic Surgery

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sheetal Sapra, Director of Dermatology, ICLS Dermatology & Plastic Surgery
• ClinicalTrials.gov Identifier: NCT02907268
• Other Study ID Numbers: ICLS-06-2013
• First Posted: Sep 20, 2016
• Last Update Posted: Oct 13, 2017
• Last Verified: Sep 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Sheetal Sapra, Director of Dermatology, ICLS Dermatology & Plastic Surgery: botulinum toxin type A, intradermal
• Additional relevant MeSH terms: Facies; Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Arm/Group Title	Treatment Arm A	Treatment Arm B
Arm/Group Description	The first treatment group received onabotulinumtoxinA (Botox) on the right side of their face and abobotulinumtoxinA (Dysport) on the left side of their face. Baseline treatment at Week 0 included the intradermal injection of onabotulinumtoxinA on one side of the face and abobotulinumtoxinA on the other. Patients were treated at Week 2 with traditional intramuscular injections consisting of onabotulinumtoxinA on the same side of their face as at Week 0 and abobotulinumtoxinA on the other side. Patients were treated based on individual need, and thus the treatment volumes were not controlled or standardized. onabotulinumtoxinA: OnabotulinumtoxinA (Botox; Allergan) was approved by the FDA in 2002. Intervention administered by study nurse. Administered in a regular 1 cm2 grid across the cheeks and forehead. abobotulinumtoxinA: AbobotulinumtoxinA (Dysport; Galderma) was approved by the FDA in 2009. Intervention administered by study nurse. Administered in a regular 1 cm2 grid across	The second treatment group received abobotulinumtoxinA (Dysport) on the right side of their face and onabotulinumtoxinA (Botox) on the left side of their face. Baseline treatment at Week 0 included the intradermal injection of onabotulinumtoxinA on one side of the face and abobotulinumtoxinA on the other. Patients were treated at Week 2 with traditional intramuscular injections consisting of onabotulinumtoxinA on the same side of their face as at Week 0 and abobotulinumtoxinA on the other side. Patients were treated based on individual need, and thus the treatment volumes were not controlled or standardized. onabotulinumtoxinA: OnabotulinumtoxinA (Botox; Allergan) was approved by the FDA in 2002. Intervention administered by study nurse. Administered in a regular 1 cm2 grid across the cheeks and forehead. abobotulinumtoxinA: AbobotulinumtoxinA (Dysport; Galderma) was approved by the FDA in 2009. Intervention administered by study nurse. Administered in a regular 1 cm2 grid across
Period Title: Overall Study
STARTED	5	5
COMPLETED	5	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Treatment Arm A	Treatment Arm B	Total
Arm/Group Description	The first treatment group received onabotulinumtoxinA (Botox) on the right side of their face and abobotulinumtoxinA (Dysport) on the left side of their face. Baseline treatment at Week 0 included the intradermal injection of onabotulinumtoxinA on one side of the face and abobotulinumtoxinA on the other. Patients were treated at Week 2 with traditional intramuscular injections consisting of onabotulinumtoxinA on the same side of their face as at Week 0 and abobotulinumtoxinA on the other side. Patients were treated based on individual need, and thus the treatment volumes were not controlled or standardized. OnabotulinumtoxinA was approved by the FDA in 2002. AbobotulinumtoxinA was approved by the FDA in 2009. Intervention administered by study nurse. Intradermal administered in a regular 1 cm2 grid across the cheeks and forehead. Intramuscular administered according to normal practice.	The second treatment group received abobotulinumtoxinA (Dysport) on the right side of their face and onabotulinumtoxinA (Botox) on the left side of their face. Baseline treatment at Week 0 included the intradermal injection of onabotulinumtoxinA on one side of the face and abobotulinumtoxinA on the other. Patients were treated at Week 2 with traditional intramuscular injections consisting of onabotulinumtoxinA on the same side of their face as at Week 0 and abobotulinumtoxinA on the other side. Patients were treated based on individual need, and thus the treatment volumes were not controlled or standardized. OnabotulinumtoxinA was approved by the FDA in 2002. AbobotulinumtoxinA was approved by the FDA in 2009. Intervention administered by study nurse. Intradermal administered in a regular 1 cm2 grid across the cheeks and forehead. Intramuscular administered according to normal practice.	Total of all reporting groups
Overall Participants	5	5	10
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	51.1	51.1	51.1
Sex: Female, Male (Count of Participants)
Female	5 100%	5 100%	10 100%
Male	0 0%	0 0%	0 0%
Blinded assessment of facial rhytids (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	2.5	2.8	2.7

Outcome Measures

1. Primary Outcome

Title	Blinded Assessment: Overall Change in Facial Wrinkles From Baseline to Week 2 as Assessed by a Numeric Rating Scale Based on Pre- and Post-treatment Photographs
Description	Blinded assessments of overall change in facial wrinkles from baseline to week 2 based on pre and post treatment photographs. Measured on a 5 point scale which is a static assessment of wrinkle severity. 0=wrinkles absent (minimum), 1=shallow but visible wrinkles, 2=fine lines slight indentation, 3=clear indentation 0-1mm deep, 4=moderate indentation 1-2mm deep, 5=deep indentation >2mm deep (maximum). A higher value = a worse outcome (more severe wrinkles). Includes 9 subscales measured on the same scale described above. Subscales measure wrinkle severity in the left and right forehead region, left and right cheek region, left and right crow's feet region, left and right upper lip region, and glabellar region. All scores were computed by averaging subscale ratings.
Time Frame	Baseline and 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1
Arm/Group Description	Overall change in wrinkles score. This is calculated per patient, regardless of randomization.
Measure Participants	10
Mean (Standard Deviation) [units on a scale]	-0.21 (0.39459)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1
	Comments
	Type of Statistical Test	Equivalence
	Comments	Each variable compared with the "no change" score. The "no change" score is 0 for wrinkles-related variables.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	Blinded Assessment: Overall Change in Facial Wrinkles From Baseline to Week 4 as Assessed by a Numeric Rating Scale Based on Pre- and Post-treatment Photographs
Description	Blinded assessments of overall change in facial wrinkles from baseline to week 4 based on pre and post treatment photographs. Measured on a 5 point scale which is a static assessment of wrinkle severity. 0=wrinkles absent (minimum), 1=shallow but visible wrinkles, 2=fine lines slight indentation, 3=clear indentation 0-1mm deep, 4=moderate indentation 1-2mm deep, 5=deep indentation >2mm deep (maximum). A higher value = a worse outcome (more severe wrinkles). Includes 9 subscales measured on the same scale described above. Subscales measure wrinkle severity in the left and right forehead region, left and right cheek region, left and right crow's feet region, left and right upper lip region, and glabellar region. All scores were computed by averaging subscale ratings.
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1
Arm/Group Description	Overall change in wrinkles score. This is calculated per patient, regardless of randomization.
Measure Participants	10
Mean (Standard Deviation) [units on a scale]	-0.36 (0.419042)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1
	Comments
	Type of Statistical Test	Equivalence
	Comments	Each variable compared with the "no change" score. The "no change" score is 0 for wrinkles-related variables.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Primary Outcome

Title	Blinded Assessment: Overall Change in Facial Wrinkles From Baseline to Week 16 as Assessed by a Numeric Rating Scale Based on Pre- and Post-treatment Photographs
Description	Blinded assessments of overall change in facial wrinkles from baseline to week 16 based on pre and post treatment photographs. Measured on a 5 point scale which is a static assessment of wrinkle severity. 0=wrinkles absent (minimum), 1=shallow but visible wrinkles, 2=fine lines slight indentation, 3=clear indentation 0-1mm deep, 4=moderate indentation 1-2mm deep, 5=deep indentation >2mm deep (maximum). A higher value = a worse outcome (more severe wrinkles). Includes 9 subscales measured on the same scale described above. Subscales measure wrinkle severity in the left and right forehead region, left and right cheek region, left and right crow's feet region, left and right upper lip region, and glabellar region. All scores were computed by averaging subscale ratings.
Time Frame	Baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1
Arm/Group Description	Overall change in wrinkles score. This is calculated per patient, regardless of randomization.
Measure Participants	10
Mean (Standard Deviation) [units on a scale]	-0.3889 (0.440262)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1
	Comments
	Type of Statistical Test	Equivalence
	Comments	Each variable compared with the "no change" score. The "no change" score is 0 for wrinkles-related variables.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	4 months (September 2013-January 2015)
Arm/Group Title	Treatment Arm A		Treatment Arm B
Arm/Group Description	The first treatment group received onabotulinumtoxinA (Botox) on the right side of their face and abobotulinumtoxinA (Dysport) on the left side of their face. Baseline treatment at Week 0 included the intradermal injection of onabotulinumtoxinA on one side of the face and abobotulinumtoxinA on the other. Patients were treated at Week 2 with traditional intramuscular injections consisting of onabotulinumtoxinA on the same side of their face as at Week 0 and abobotulinumtoxinA on the other side. Patients were treated based on individual need, and thus the treatment volumes were not controlled or standardized. onabotulinumtoxinA: OnabotulinumtoxinA was approved by the FDA in 2002. Intervention administered by study nurse. Administered in a regular 1 cm2 grid across the cheeks and forehead. abobotulinumtoxinA: AbobotulinumtoxinA was approved by the FDA in 2009. Intervention administered by study nurse. Administered in a regular 1 cm2 grid across the cheeks and forehead.		The second treatment group received abobotulinumtoxinA (Dysport) on the right side of their face and onabotulinumtoxinA (Botox) on the left side of their face. Baseline treatment at Week 0 included the intradermal injection of onabotulinumtoxinA on one side of the face and abobotulinumtoxinA on the other. Patients were treated at Week 2 with traditional intramuscular injections consisting of onabotulinumtoxinA on the same side of their face as at Week 0 and abobotulinumtoxinA on the other side. Patients were treated based on individual need, and thus the treatment volumes were not controlled or standardized. onabotulinumtoxinA: OnabotulinumtoxinA was approved by the FDA in 2002. Intervention administered by study nurse. Administered in a regular 1 cm2 grid across the cheeks and forehead. abobotulinumtoxinA: AbobotulinumtoxinA was approved by the FDA in 2009. Intervention administered by study nurse. Administered in a regular 1 cm2 grid across the cheeks and forehead.
All Cause Mortality
	Treatment Arm A		Treatment Arm B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Serious Adverse Events
	Treatment Arm A		Treatment Arm B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Treatment Arm A		Treatment Arm B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/5 (60%)		5/5 (100%)
Immune system disorders
Cold	0/5 (0%)	0	1/5 (20%)	1
Musculoskeletal and connective tissue disorders
Worsening inflammation at sacroiliac joint	0/5 (0%)	0	1/5 (20%)	1
Nervous system disorders
Pain during injection	0/5 (0%)	0	1/5 (20%)	1
Itchiness	1/5 (20%)	1	0/5 (0%)	0
Tension headache	0/5 (0%)	0	1/5 (20%)	1
Numbness on forehead	0/5 (0%)	0	1/5 (20%)	1
Skin and subcutaneous tissue disorders
Bruise	1/5 (20%)	1	1/5 (20%)	1
Drooping	1/5 (20%)	1	4/5 (80%)	4
Dry skin	0/5 (0%)	0	1/5 (20%)	1
Face flushed	0/5 (0%)	0	1/5 (20%)	1
Acne breakout	0/5 (0%)	0	1/5 (20%)	1
Welt on forehead	1/5 (20%)	1	1/5 (20%)	1
Stinging sensation on face	0/5 (0%)	0	1/5 (20%)	1
Left cheek looks more full	1/5 (20%)	1	0/5 (0%)	0

Limitations/Caveats

Limitations include small sample size and not having objective assessments. Insignificant p value could mean no difference detected or the sample was too small to detect difference. Blinded assessor made subjective assessments based on the photos.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.