Skin Wrinkling
Conditions
Keywords
wrinkles, botulinum toxin, abobotulinumtoxinA, onabotulinumtoxinA, field of anhydrotic effects
Brief summary
The purpose of this study is to assess the fields of anhydrotic effect (FAE) of abobotulinumtoxinA and onabotulinumtoxinA at the same labeled unit dose (1:1 units), comparing both sweat gland and muscle activity.
Detailed description
This is a prospective, single-center, randomized, double-blind study. All participants were recruited from a research center in Porto Alegre, Brazil, and provided written informed consent. The purpose of this study is to assess the fields of anhydrotic effect (FAE) of abobotulinumtoxinA and onabotulinumtoxinA at the same labeled unit dose (1:1 units), comparing both sweat gland and muscle activities. Nineteen patients were enrolled and evaluations were performed at baseline and 28 days after treatment.
Interventions
DRUGAbobotulinumtoxinA (ABO)
Isovolumetric (0.02 mL) doses of 2 units of abobotulinumtoxinA injected on one side of the forehead.
DRUGOnabotulinumtoxinA (ONA)
Isovolumetric (0.02 mL) doses of 2 units of onabotulinumtoxinA injected on the other side of the forehead.
Sponsors
Hexsel Dermatology Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Signed consent 2. Female subjects aged between 18 to 60 years 3. Phototype I to IV 4. Moderate to severe wrinkles in the forehead region on maximal contracture of the frontalis muscle according to the Wrinkle Severity Scale 5. Subjects with the Minor Test\* considered positive from grade 3 to 5 on the Minor test sweat intensity scale, showing sweat on the forehead under standardized conditions 6. Medical history and clinical examination that, in the investigator's opinion, do not prevent the subject from participating in the study or from using the proposed medication 7. Negative urinary pregnancy test at the initial visit for women of childbearing potential 8. Use of an effective contraceptive method (oral or injectable contraception, abstinence, intrauterine device, diaphragm, hysterectomy or bilateral ovariectomy, tubal attachment, condom, sponge, spermicide or partner with vasectomy) throughout the study for women of childbearing potential 9. Subjects must agree not to undergo other dermatological or aesthetic treatments during the study period \*The Minor test must be the last test to be done. Only the subjects who fulfill all the inclusion criteria above undergo the Minor test to check for sweating in the frontal region. The graduation considered positive for inclusion in the study will be 3 to 5. Inclusion Criteria: 1. Pregnancy or intention to become pregnant during the study period 2. Breastfeeding 3. Botulinum toxin treatments in the last 6 months 4. Subjects participating in other clinical studies 5. Any surgical procedure performed that has affected the frontal or orbicularis muscle, previous blepharoplasty or eyebrow raising 6. Any cosmetic procedures, including fillers, or scars that may interfere with the results of the study 7. Fronto-parietal alopecia according to the Norwood-Hamilton classification 8. Neoplastic, muscular or neurological diseases 9. Use of using aminoglycoside antibiotics or penicillamines, quinine or calcium channel blockers or that they will use at any time during the study 10. Inflammatory or infectious processes at the application site 11. Evident facial asymmetry 12. History of adverse event, such as sensitivity to the components of the formula, ptosis or any other adverse event that, in the investigator's opinion, prevents the research subject from participating in the study 13. Myasthenia Gravis, Eaton-Lambert Syndrome and motor neuron disease 14. Coagulation disorders or use of anticoagulants 15. Autoimmune disease 16. History of poor adherence to treatments or who have shown lack of cooperation to adhere to the study protocol 17. Any condition that, in the investigator's opinion, could compromise the results of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Horizontal Diameter of the Fields of Anhidrotic Effect | 28 days | The Horizontal Diameter of the Fields of Anhidrotic Effect were measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The reaction of iodine and starch with the sweat (Minor's test) allows visualizing the field of anhidrotic effects and measuring them. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FAE are observed at baseline. |
| Vertical Diameter of the Fields of Anhidrotic Effect | 28 days | The Vertical Diameter of the Fields of Anhidrotic Effect were measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The reaction of iodine and starch with the sweat (Minor's test) allows visualizing the field of anhidrotic effects and measuring them. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FAE are observed at baseline. |
| Area of the Fields of Anhidrotic Effect | 28 days | The area of the Fields of Anhidrotic Effect were measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The reaction of iodine and starch with the sweat (Minor's test) allows visualizing the field of anhidrotic effects and measuring them. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FAE are observed at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Wrinkle Severity Scale (WSS) at Maximum Contraction | Baseline and 28 days | It is a 4-point validated scale for forehead lines: 0 - None 1. \- Mild 2. \- Moderate 3. \- Severe The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The muscular effect reduction can be observed by the reduction of facial lines. Wrinkle scales are used to grade the muscular effects of botulinum toxin. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FME are observed at baseline. |
| Wrinkle Severity Scale (WSS) at Rest | Baseline and 28 days | It its a 4-point validated scale for forehead lines: 0 - None 1. \- Mild 2. \- Moderate 3. \- Severe The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The muscular effect reduction can be observed by the reduction of facial lines. Wrinkle scales are used to grade the muscular effects of botulinum toxin. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FME are observed at baseline. |
| Evoked Compound Muscle Action Potentials (ECMAP) | Baseline and 28 days | Amplitude of the evoked compound muscle action potentials in the frontalis muscle on stimulation of the facial nerve performed at baseline and visit 2 using surface electrodes on the forehead and electrical stimulation of the facial nerve according to standard neurophysiologic procedures. The amplitude of the ECMAP was performed by an experienced neurologist using an electromyography device (Teca Sapphire; Teca Corp). |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A Patients received 2U/0.02mL of reconstituted abobotulinumtoxinA on the right side of the forehead and 2U/0.02mL of reconstituted onabotulinumtoxinA on the left side. | 9 |
| Group A Patients received 2U/0.02mL of reconstituted abobotulinumtoxinA on the right side of the forehead and 2U/0.02mL of reconstituted onabotulinumtoxinA on the left side. | 18 |
| Group B Patients received 2U/0.02mL of reconstituted abobotulinumtoxinA on the left side of the forehead and 2U/0.02mL of reconstituted onabotulinumtoxinA on the right side. | 10 |
| Group B Patients received 2U/0.02mL of reconstituted abobotulinumtoxinA on the left side of the forehead and 2U/0.02mL of reconstituted onabotulinumtoxinA on the right side. | 20 |
| Total | 57 |
Baseline characteristics
| Characteristic | Group A | Total | Group B |
|---|---|---|---|
| Age, Continuous | 42.7 years STANDARD_DEVIATION 10.6 | 39.0 years STANDARD_DEVIATION 10.2 | 35.7 years STANDARD_DEVIATION 9.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 19 Participants | 10 Participants |
| Region of Enrollment Brazil | 9 Participants | 19 Participants | 10 Participants |
| Sex: Female, Male Female | 9 Participants | 19 Participants | 10 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 | 2 / 19 | 1 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 |
Outcome results
Primary
Area of the Fields of Anhidrotic Effect
The area of the Fields of Anhidrotic Effect were measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The reaction of iodine and starch with the sweat (Minor's test) allows visualizing the field of anhidrotic effects and measuring them. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FAE are observed at baseline.
Time frame: 28 days
Population: Per protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abobotulinumtoxin A | Area of the Fields of Anhidrotic Effect | 0.86 centimeters squared | Standard Deviation 0.22 |
| Onabotulinumtoxin A | Area of the Fields of Anhidrotic Effect | 1.49 centimeters squared | Standard Deviation 0.49 |
Primary
Horizontal Diameter of the Fields of Anhidrotic Effect
The Horizontal Diameter of the Fields of Anhidrotic Effect were measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The reaction of iodine and starch with the sweat (Minor's test) allows visualizing the field of anhidrotic effects and measuring them. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FAE are observed at baseline.
Time frame: 28 days
Population: Per protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abobotulinumtoxin A | Horizontal Diameter of the Fields of Anhidrotic Effect | 0.84 centimeters | Standard Deviation 0.14 |
| Onabotulinumtoxin A | Horizontal Diameter of the Fields of Anhidrotic Effect | 1.24 centimeters | Standard Deviation 0.24 |
Primary
Vertical Diameter of the Fields of Anhidrotic Effect
The Vertical Diameter of the Fields of Anhidrotic Effect were measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The reaction of iodine and starch with the sweat (Minor's test) allows visualizing the field of anhidrotic effects and measuring them. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FAE are observed at baseline.
Time frame: 28 days
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abobotulinumtoxin A | Vertical Diameter of the Fields of Anhidrotic Effect | 1.19 centimeters | Standard Deviation 0.19 |
| Onabotulinumtoxin A | Vertical Diameter of the Fields of Anhidrotic Effect | 1.50 centimeters | Standard Deviation 0.26 |
Secondary
Evoked Compound Muscle Action Potentials (ECMAP)
Amplitude of the evoked compound muscle action potentials in the frontalis muscle on stimulation of the facial nerve performed at baseline and visit 2 using surface electrodes on the forehead and electrical stimulation of the facial nerve according to standard neurophysiologic procedures. The amplitude of the ECMAP was performed by an experienced neurologist using an electromyography device (Teca Sapphire; Teca Corp).
Time frame: Baseline and 28 days
Population: Per protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abobotulinumtoxin A | Evoked Compound Muscle Action Potentials (ECMAP) | Baseline | 1108.17 microvolts | Standard Deviation 364.76 |
| Abobotulinumtoxin A | Evoked Compound Muscle Action Potentials (ECMAP) | Day 28 | 202.89 microvolts | Standard Deviation 258.44 |
| Onabotulinumtoxin A | Evoked Compound Muscle Action Potentials (ECMAP) | Baseline | 1079.11 microvolts | Standard Deviation 266.02 |
| Onabotulinumtoxin A | Evoked Compound Muscle Action Potentials (ECMAP) | Day 28 | 165.39 microvolts | Standard Deviation 232.1 |
Secondary
Wrinkle Severity Scale (WSS) at Maximum Contraction
It is a 4-point validated scale for forehead lines: 0 - None 1. \- Mild 2. \- Moderate 3. \- Severe The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The muscular effect reduction can be observed by the reduction of facial lines. Wrinkle scales are used to grade the muscular effects of botulinum toxin. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FME are observed at baseline.
Time frame: Baseline and 28 days
Population: Per protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | Baseline - Grade 0 | 0 participants |
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | Baseline - Grade 1 | 0 participants |
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | Baseline - Grade 2 | 7 participants |
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | Baseline - Grade 3 | 11 participants |
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | At 28 days - Grade 0 | 5 participants |
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | At 28 days - Grade 1 | 10 participants |
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | At 28 days - Grade 2 | 2 participants |
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | At 28 days - Grade 3 | 1 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | At 28 days - Grade 3 | 1 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | Baseline - Grade 0 | 0 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | At 28 days - Grade 0 | 6 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | Baseline - Grade 1 | 0 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | At 28 days - Grade 2 | 3 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | Baseline - Grade 2 | 6 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | At 28 days - Grade 1 | 8 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Maximum Contraction | Baseline - Grade 3 | 12 participants |
Secondary
Wrinkle Severity Scale (WSS) at Rest
It its a 4-point validated scale for forehead lines: 0 - None 1. \- Mild 2. \- Moderate 3. \- Severe The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The muscular effect reduction can be observed by the reduction of facial lines. Wrinkle scales are used to grade the muscular effects of botulinum toxin. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FME are observed at baseline.
Time frame: Baseline and 28 days
Population: Per protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | Baseline - Grade 0 | 1 participants |
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | Baseline - Grade 1 | 8 participants |
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | Baseline - Grade 2 | 4 participants |
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | Baseline - Grade 3 | 5 participants |
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | At 28 days - Grade 0 | 10 participants |
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | At 28 days - Grade 3 | 0 participants |
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | At 28 days - Grade 1 | 6 participants |
| Abobotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | At 28 days - Grade 2 | 2 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | At 28 days - Grade 1 | 6 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | Baseline - Grade 0 | 1 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | At 28 days - Grade 0 | 10 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | Baseline - Grade 1 | 7 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | At 28 days - Grade 3 | 0 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | Baseline - Grade 2 | 5 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | At 28 days - Grade 2 | 2 participants |
| Onabotulinumtoxin A | Wrinkle Severity Scale (WSS) at Rest | Baseline - Grade 3 | 5 participants |