Botulinum Toxin A Single Blind Split-Face Randomized Pilot Study

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

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.

Study Overview

• Status: Completed
• Conditions: Facial Rhytids
• Intervention / Treatment: Drug: onabotulinumtoxinA; Drug: abobotulinumtoxinA

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Baseline and 2 weeks
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	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.	Baseline and 4 weeks
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	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.	Baseline and 16 weeks

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Sapra P, Demay S, Sapra S, Khanna J, Mraud K, Bonadonna J. 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. J Clin Aesthet Dermatol. 2017 Feb;10(2):34-44. Epub 2017 Feb 1.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: September 8, 2016
• First Submitted That Met QC Criteria: September 15, 2016
• First Posted (Estimate): September 20, 2016

Study Record Updates

• Last Update Posted (Actual): October 13, 2017
• Last Update Submitted That Met QC Criteria: September 12, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: botulinum toxin type A, intradermal
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Facies; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: ICLS-06-2013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Photographs of individual participants are included in presentations and publications. Consent to reproduce photographs has been obtained from all participants. No other IPD is planned to be shared unless requested.