Wrinkles in Frontal Area
Conditions
Keywords
Muscular activity, wrinkles in frontal area, action halos
Brief summary
The objective of this study is to compare the action halos 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. Fifty nine female patients, presenting with moderate to severe forehead wrinkles, with sweating ability who had never undergone previous BoNT-A injections were enrolled. There were two randomizations, one related to the dose-equivalence (2:1U and 2.5:1U), both reconstituted in the same volume of 0.02 mL per point and another related to the forehead side (left or right) for application of the tested drugs. Baseline, twenty-eight and 112 days later, clinical and photographic assessments, Minor´s test, and electromyographic (EMG) evaluations were performed.
Interventions
DRUGBOTULINUM TOXIN TYPE-A
On Visit 1 (Day 0): Botulinum toxin A (Dysport® and Botox®) 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. * Botox® : 2 units will be injected in the left or right forehead side.(opposite side of dysport injection)
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 | Minor's test permits the visualization of the effect of botulinum toxin in the injected area,also called action halos. Mirror is a computer program that allows, through photogrpahs, measuring the horizontal diameter and the area of action halos. |
| ECMAP in m. Frontialis BoNT A1(4U) X BoNT A2 (2U) | 28 days | ECMAP(Evoked Compound Muscle Action Potentials) was accessed by an electromyography (EMG) device (TECA Sapphire - TECA Corp., Pleasantville, NY). |
| Horizontal Action Halo Diameter at 112 Days | 112 days | Minor's test permits the visualization of the effect of botulinum toxin in the injected area,also called action halos. Mirror is a computer program that allows, through photogrpahs, measuring the horizontal diameter and the area of action halos. |
Countries
Brazil
Participant flow
Recruitment details
Recruitment process: It is planned to recruit a total of 58 subjects at one single centre, Brazilian Center For Studies in Dermatology, in Porto Alegre, Brazil. The anticipated drop out rate is 10%. Baseline evaluation: May 2005 to July 2007.
Pre-assignment details
13 volunteers were excluded; (screen failure) Iodine allergy=2 Minor´s Test failure=6 Mild wrinkles=3 Inclusion criteria failure=2
Participants by arm
| Arm | Count |
|---|---|
| BoNT A1(4U) Group 1: Botulinum toxin A (Dysport®) will be administered 4 units of Dysport® | 30 |
| BoNT-A2(2U) Group 2: Botulinum toxin A (Botox®) will be administered 2 units of Botox® | 29 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | BoNT A1(4U) | BoNT-A2(2U) | Total |
|---|---|---|---|
| Age Continuous | 44.77 years STANDARD_DEVIATION 8.67 | 41.86 years STANDARD_DEVIATION 11.98 | 42.88 years STANDARD_DEVIATION 10.54 |
| Sex: Female, Male Female | 30 Participants | 29 Participants | 59 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 26 | 0 / 26 |
| serious Total, serious adverse events | 0 / 26 | 0 / 26 |
Outcome results
Primary
ECMAP in m. Frontialis BoNT A1(4U) X BoNT A2 (2U)
ECMAP(Evoked Compound Muscle Action Potentials) was accessed by an electromyography (EMG) device (TECA Sapphire - TECA Corp., Pleasantville, NY).
Time frame: 28 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BoNT A1(4U) | ECMAP in m. Frontialis BoNT A1(4U) X BoNT A2 (2U) | 276.18 microvolts | Standard Deviation 319.15 |
| BoNT-A2(2U) | ECMAP in m. Frontialis BoNT A1(4U) X BoNT A2 (2U) | 289.00 microvolts | Standard Deviation 303.86 |
p-value: 0.658t-test, 2 sided
p-value: 0.739t-test, 2 sided
Primary
Horizontal Action Halo Diameter at 112 Days
Minor's test permits the visualization of the effect of botulinum toxin in the injected area,also called action halos. Mirror is a computer program that allows, through photogrpahs, measuring the horizontal diameter and the area of action halos.
Time frame: 112 days
Population: Intention to treat analysis. 55 volunteers - One drop out from visit 2 (28 days) to visit 3 (112 days): 54 volunteers.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BoNT A1(4U) | Horizontal Action Halo Diameter at 112 Days | 0.8742 centimeter | Standard Deviation 0.3333 |
| BoNT-A2(2U) | Horizontal Action Halo Diameter at 112 Days | 1.1196 centimeter | Standard Deviation 0.262 |
p-value: 0.184t-test, 2 sided
Primary
Horizontal Action Halo Diameter at 28 Days
Minor's test permits the visualization of the effect of botulinum toxin in the injected area,also called action halos. Mirror is a computer program that allows, through photogrpahs, measuring the horizontal diameter and the area of action halos.
Time frame: 28 days
Population: The analysis was intention to treat (ITT); One drop out, from baseline to visit 1(intervention) and 3 drop outs from visit 1 to visit 2 (28 days after botulinum toxin injections). Started 59 volunteers - 4 drop outs, there was 55 volunteers in the first analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BoNT A1(4U) | Horizontal Action Halo Diameter at 28 Days | 1.0526 centimeter | Standard Deviation 0.3638 |
| BoNT-A2(2U) | Horizontal Action Halo Diameter at 28 Days | 1.0670 centimeter | Standard Deviation 0.2239 |
p-value: 0.832t-test, 2 sided