Wrinkles in Frontal Area
Conditions
Keywords
Botulinum toxin type A, field effects, dose-equivalence, anhydrotic action halos
Brief summary
The objective of this study is to compare the field of effects of the botulinum toxins (Dysport® and Botox®) using two equivalence-ratios and to gather supportive information, such as more detailed data on the effectiveness in reduction of wrinkles and duration of action on the upper part of the face of both products, trough scales and photographs evaluations.
Detailed description
This was a monocentric, prospective, randomized and double-blind study. Twenty nine female patients, presenting with moderate to severe forehead wrinkles, with sweating ability who had never undergone previous BoNT-A injections were enrolled. Subjects have received botulinum toxin type-A injections in two forehead sites, Botox 2U and Dysport 5U, both reconstituted in the same volume of 0.02 mL per point. Baseline, twenty-eight and 112 days later, clinical and photographic assessments, Minor´s test, and electromyographic (EMG) evaluations were performed.
Interventions
Botulinum toxin A (Dysport®)will be administered according to an equivalence ratio of 2,5:1. Both reconstituted in the same volume per point, injected in the forehead determined site. -Dysport®: 5 units will be injected in the left or right forehead side.
DRUGBotulinum Toxin Type A/Botox®
2 units will be injected in the left or right forehead side.(opposite side of dysport injection)
DRUGBotulinum Toxin Type A/Dysport®
Botulinum toxin A (Dysport®)will be administered according to an equivalence ratio of 2:1. Both reconstituted in the same volume per point, injected in the forehead determined site. -Dysport®: 4 units will be injected in the left or right forehead side, 2:1 ratio Dysport/Botox.
Sponsors
Hexsel Dermatology Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Written Informed Consent (Annex 1) 2. Female 3. Subjects agreeing to take part in all procedures of the study, including botulinum toxin applications, Minor's test, measurement of Evoked Potentials, photographs, etc.), after being fully informed on the objectives and nature of the investigations 4. Subjects aged between 18 and 60 years 5. Subjects presenting with moderate to severe wrinkles on the forehead under maximum voluntary contraction of the m. frontalis 6. Subjects with positive Minor's test showing sweating on the forehead in standardized conditions described in Annex 2 \*The Minor's Test will be the last inclusion criterion to be evaluated. Only these patients eligible according to the other inclusion criteria will undergo the Minor's Test to evaluate their sweating on the forehead. The cut off point is a positive Minor's Test (Level +1) - only subjects with Minor's Test (Level +1) will be recruited in the study (Annex 2). 7. Medical history and physical examination which, based on the investigator's opinion, do not prevent the patient from taking part in the study and use the products under investigation 8. Subjects of childbearing age should present a negative urine pregnancy test at baseline and should be using an effective contraceptive method; 9. Availability of the patient throughout the duration of the study (112 days) 10. Subject agrees not to undergo other cosmetic or dermatological procedures during the study 11. Subjects with sufficient schooling and awareness to enable them to cooperate to the degree required by this protocol
Exclusion criteria
1. Pregnant women or women intending to become pregnant in the next 4 months after screening for eligibility 2. Subjects who are lactating 3. Subjects having undergone botulinum toxin treatment within the last 6 months 4. Subjects participating in other clinical trials 5. Any prior surgery affecting the frontalis and/or orbicularis muscles, prior blepharoplasty or brow lift 6. Any prior cosmetic procedures, including fillers, or scars that may interfere with the study results 7. Subjects presenting fronto-parietal alopecia according to the Norwood-Hamilton classification 8. Subjects with neoplastic, muscular or neurological diseases 9. Subjects using aminoglycoside and penicillamine antibiotics, quinine and Ca2+ channel blockers 10. Subjects with inflammation or active infection in the area to be injected 11. Subjects presenting evident facial asymmetry 12. Subjects with a history of adverse effects, such as sensitivity to the components of the formula, ptosis or any other adverse effect, which in the investigator's opinion should prevent the patient from participating in the study 13. Subjects presenting myasthenia gravis, Eaton-Lambert Syndrome and motor neuron diseases 14. Subjects with coagulation disorders or using anticoagulants 15. Subjects with known systemic autoimmune diseases 16. Subjects with a history of medical treatment non-adherence or showing unwillingness to adhere to the study protocol 17. Any condition that, in the opinion of the investigator, can compromise the evaluation of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Horizontal Action Halo Diameter at 28 Days | 28 Days | The colorful complex formed by Minor's test allows the visualization of the area covered by the effects of botulinum toxin on sweat glands, also known as action halos. The horizontal diameter at day 28 were expressed in centimeters and quantified by the software Mirror® (Canfield Scientific Inc., USA). |
| Horizontal Action Halo Diameter at 112 Days | 112 days | The colorful complex formed by Minor's test allows the visualization of the area covered by the effects of botulinum toxin on sweat glands, also known as action halos. The horizontal diameter at day 112 were expressed in centimeters and quantified by the software Mirror® (Canfield Scientific Inc., USA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ECMAP in m. Frontialis | 28 days | The measurement of the ECMAP(Evoked Compound Muscle Action Potentials) used surface electrodes on the forehead and electrical stimulation of the facial nerve, according to standard neurophysiological procedures. The amplitude of the ECMAP in the m. frontalis on stimulation of the facial nerve was performed by an experienced neurologist. ECMAP was assessed by an electromyography (EMG) device (TECA Sapphire - TECA Corp., Pleasantville, NY). |
Countries
Brazil
Participant flow
Recruitment details
A total of 29 subjects was recruited at Brazilian Center For Studies in Dermatology, in Porto Alegre, Brazil. The anticipated drop out rate is 10%. Participants were their own control, because on one side of frontal region they have received 5U of botulinum toxin - Dysport and on other side 4U of botulinum toxin - Botox;
Pre-assignment details
13 volunteers were excluded; Screen failure: Iodine allergy = 2; Minor´s Test failure = 6 Mild wrinkles = 3 Inclusion criteria failure = 2 Minor's test allows the visualization of the area covered by the effects of botulinum toxin on sweat glands also known as action halos.
Participants by arm
| Arm | Count |
|---|---|
| Dysport® 5U/ Botox® 2U Botulinum toxin A (Dysport®) 5 U Subjects have received one injection of five units of botulinum toxin , called Dysport® on one side in the frontal region, that the other brand Botox® was administered two units to the other side of the frontal region. | 29 |
| Total | 29 |
Baseline characteristics
| Characteristic | Dysport® 5U/ Botox® 2U |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 29 |
| serious Total, serious adverse events | 0 / 29 |
Outcome results
Primary
Horizontal Action Halo Diameter at 112 Days
The colorful complex formed by Minor's test allows the visualization of the area covered by the effects of botulinum toxin on sweat glands, also known as action halos. The horizontal diameter at day 112 were expressed in centimeters and quantified by the software Mirror® (Canfield Scientific Inc., USA).
Time frame: 112 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dysport® 5U | Horizontal Action Halo Diameter at 112 Days | 1.12 centimeter | Standard Deviation 0.26 |
| Botox® 2U | Horizontal Action Halo Diameter at 112 Days | 0.96 centimeter | Standard Deviation 0.29 |
p-value: 0.003t-test, 2 sided
Primary
Horizontal Action Halo Diameter at 28 Days
The colorful complex formed by Minor's test allows the visualization of the area covered by the effects of botulinum toxin on sweat glands, also known as action halos. The horizontal diameter at day 28 were expressed in centimeters and quantified by the software Mirror® (Canfield Scientific Inc., USA).
Time frame: 28 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dysport® 5U | Horizontal Action Halo Diameter at 28 Days | 1.28 centimeter | Standard Deviation 0.26 |
| Botox® 2U | Horizontal Action Halo Diameter at 28 Days | 1.12 centimeter | Standard Deviation 0.31 |
Comparison: In this study the null hypothesis was that BoNT-A1 had the same effect (halus)than the BoNT-A2.p-value: <0.0001t-test, 2 sided
Secondary
ECMAP in m. Frontialis
The measurement of the ECMAP(Evoked Compound Muscle Action Potentials) used surface electrodes on the forehead and electrical stimulation of the facial nerve, according to standard neurophysiological procedures. The amplitude of the ECMAP in the m. frontalis on stimulation of the facial nerve was performed by an experienced neurologist. ECMAP was assessed by an electromyography (EMG) device (TECA Sapphire - TECA Corp., Pleasantville, NY).
Time frame: 28 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dysport® 5U | ECMAP in m. Frontialis | 492.53 microvolts | Standard Deviation 290.7 |
| Botox® 2U | ECMAP in m. Frontialis | 468.27 microvolts | Standard Deviation 263.31 |
p-value: 0.61t-test, 2 sided
Secondary
ECMAP in m. Frontialis
The measurement of the ECMAP(Evoked Compound Muscle Action Potentials) used surface electrodes on the forehead and electrical stimulation of the facial nerve, according to standard neurophysiological procedures. The amplitude of the ECMAP in the m. frontalis on stimulation of the facial nerve was performed by an experienced neurologist. ECMAP was assessed by an electromyography (EMG) device (TECA Sapphire - TECA Corp., Pleasantville, NY).
Time frame: 112 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dysport® 5U | ECMAP in m. Frontialis | 482.63 microVolts | Standard Deviation 279.58 |
| Botox® 2U | ECMAP in m. Frontialis | 539.16 microVolts | Standard Deviation 387.72 |
p-value: 0.36t-test, 2 sided