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Onabotulinumtoxin A and Hyaluronic Acid Fillers in the Treatment of Facial Paralysis

Primary Purpose

Hemifacial Paralysis

Status
Recruiting
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Juvederm
Vistabex
Sponsored by
Azienda Ospedaliera Universitaria Integrata Verona
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemifacial Paralysis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Aged > 18 years and < 65 years
  2. Hemifacial paralysis from 3 to 6 on the House-Brackmann scale
  3. Never treated with HA and BTX injection
  4. Signed informed consent
  5. Women of childbearing potential will only be included in the study if uptaking hightly effective birth control measures.

Exclusion Criteria:

  1. Hypersensitivity to any component of the products used
  2. Diabetes, systemic disease, coronary artery disease, acute-chronic hepatitis C, autoimmune disease and/or other disease involving poor general health clotting problem. Peripheric neuro-musculars disorders, amyotrophic lateral sclerosis.
  3. Pregnant or lactating

Sites / Locations

  • Azienda Ospedaliera Universitaria IntegrataRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Hyaluronic Acid filler and Botulinum Toxin group

Control group

Arm Description

Hyaluronic Acid filler: Juvederm Volbella: it will be used in the softer soft tissue, beacuse its reology is the softest Juvederm Volift: it will be used in malar area, because its reology is intermediate between the three products Juvederm Voluma: il will be used unstructured area bacause it has the best rheologic characteristics in the reintegration of loss of tissue. The differents products are going to use in different areas, depending on the area of the paralysis. Botulinum Toxin: Vistabex (50U/vial): it is going to be used in the controlateral area of the paralysed face, in order to relax muscle hyper-tonicity. Dosage and administration steps will be selected according to the clinical situation.

The control group will undergo at the same examinations of the treated group but it will not be subjected to any treatment.

Outcomes

Primary Outcome Measures

House-Brackmann scale
Change from baseline House-Brackmann score at day 270 will be assessed and then compared between the trial groups. The House-Brackmann score is a score to grade the degree of nerve damage in a facial nerve palsy. The measurement is determined by measuring the upwards (superior) movement of the mid-portion of the top of the eyebrow, and the outwards (lateral) movement of the angle of the mouth. Ti is consist of VI level: Grade I - Normal; Grade II - Slight Dysfunction; Grade III - Moderate Dysfunction; Grade IV - Moderate Severe Dysfunction; Grade V - Severe Dysfunction; Grade VI - Total Paralysis

Secondary Outcome Measures

Facial Appearance
Facial Appearance will be assessed by FACE-Q Appearance scale measuring different concepts: Area Under Chin, Cheeks, Crows' Feet, Eyes, Forehead & Eyebrows,Lines Between Eyebrows, Lip Lines, Lower Eyelids, Marionette Line, Neck, Nostrils, Upper Eyelids, Cheekbones, Chin, Eyelashes, Face Overall, Forehead Lines, Lines Overall, Lips, Lower Face & Jawline, Nasolabial Folds, Nose, Skin. Each scale is composed of a series of items (or questions) that evaluate a concept of interest. Patient responses to items are on a four-point scale and are asked to answer with their face/facial appearance in mind. Answers for a scale are summed and converted to a score from 0 to 100. A higher score indicates a better outcome.
Health-Related Quality of Life
Health-Related Quality of Life will be assessed by FACE-Q Quality of Life scale measuring different concepts: Age Visual Analogue (score ranging from -15 to +15), Aging Appraisal, Appearance-Related Distress, Early Life Impact of Treatment, Expectations, Psychological Function, Recovery Early Symptoms, Decision Satisfaction, Outcome Satisfaction,Social Function. Each scale is composed of a series of items (or questions) that evaluate a concept of interest. Patient responses to items are on a four-point scale. Answers for a scale are summed and converted to a score from 0 to 100. For most of these scales, a higher score indicates a better outcome.
Adverse Effects
Adverse Effects related to different parts of the face (Cheeks, Lower Face, Neck, Eyes, Forehead, Eyebrows, Scalp, Lips, Nose, Skin) will be assessed by FACE-Q Adverse Effects scales. Each scale is composed of a series of items (or questions) that evaluate a parts of the face. Patient responses to items are on a three/four-point scale. Answers for a scale are summed and converted to a score from 0 to 100. A higher score indicates a better outcome.
Patients experience of care
Patients experience of care related to satisfaction with information, medical team, office staff and with doctor/surgeon will be assessed by FACE-Q experience of care scales. Each scale is composed of a series of items (or questions) that evaluate the satisfaction. Patient responses to items are on a four-point scale. Answers for a scale are summed and converted to a score from 0 to 100. For all these scales, a higher score indicates a better outcome.
Facial symmetry
Facial symmetry will be performed through the analisys of 3D-photography implemented with a face grid, that allows the quantification of symmetry of the face. The face grid permits to calculate the distance in millimeters of two points from the midline (both in vertical and horizontal direction).
Facial aesthetic
Facial aesthetic will be evaluated through the analysis of 3D-photography implemented with a face grid and the Arnett's aesthetic analysis, in order to appreciate the improvement of facial aesthetic.
Facial aesthetic - thickness of soft tissue
The thickness of soft tissue will be evaluated using MRI and US (millimetric quantification of the thickness of different areas)
Facial aesthetic - thickness of hard tissue
The thickness of hard tissue will be evaluated using CBCT (millimetric quantification of the thickness of the different areas)
Facial aesthetic - tropism of muscles
The tropism of muscles will be evaluated using US and cathegorized in atrophy, hypotrophy, eutrophy, hypertrophy.
Facial aesthetic - patho-physiological condition
The patho-physiological condition will be evaluated throught an histological analysis that provides a qualitative analysis of injected and not injected tissue and specifically the effects on the fiber muscles
Hystological analysis
% of patients with tissue changes assessed by hystological analysis using scanning electron microscope and/or transmission electron microscope provides a through examination of tissue changes due to the physical introduction of the products, comparing different conditions in injected and not-injected tissue and eventually any effect on the fiber muscles.
EMG
EMG provides eletric potentials of the facial neuromuscular complex in order to evaluate the activity and symmetry oh their function.
Adverse Events
Registration of number and type of adverse events

Full Information

First Posted
June 25, 2021
Last Updated
May 10, 2022
Sponsor
Azienda Ospedaliera Universitaria Integrata Verona
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1. Study Identification

Unique Protocol Identification Number
NCT05012566
Brief Title
Onabotulinumtoxin A and Hyaluronic Acid Fillers in the Treatment of Facial Paralysis
Official Title
Clinical, Instrumental and Histological Evaluation of the Combined Use of Onabotulinumtoxin A and Hyaluronic Acid Fillers in Patients With Facial Paralysis
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 14, 2021 (Actual)
Primary Completion Date
July 14, 2023 (Anticipated)
Study Completion Date
July 14, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Azienda Ospedaliera Universitaria Integrata Verona

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
Social interaction via facial mimic expression is crucial in human relationship and communication. Neural function disorder in this mechanism therefore affects human communication and social interaction. Facial nerve palsy is the paralysis of any structure innervated by the facial nerve, thus inibiting and severely compromising facial expression. In the last decade a new algorithm of treatment of facial paralysis has been raised. It connects the expertise of Aesthetic Medicine with the expertise of Plastic and Reconstructive Surgery. It is based on the use of Botulinum Toxin (BT) and Hyaluronic Acid (HA fillers). Botulinum toxin is a paralytic toxin that determine flaccid paralysis and is nowadays used in the static correction of facial paralysis with minimal invasiveness, optimal results and no time consumption. The HA fillers has the ability to restore facial volume loss and it is used in the treatment of facial palsy to harmonize symmetry. The aim is to study the effects of the BT and HA in facial paralysis patients in order to understand the efficacy of these products that have never been injected together in this type of patients. Primary objective. To evaluate the functional improvement of facial asymmetries due to facial nerve lesion after the treatment with OnabotulinumtoxinA and hyaluronic acid fillers compared with the untreated group. The evaluation will be performed analyzing the two groups at the baseline (visit 0) and the end of the treatment period (visit 5, after 9 months). Improvement difference of at least 1 grade on the House-Brackmann scale, compared with the untreated group, will be considered clinically significant. Methods. The investigation is randomized open lab phase II single centre clinical trial. This experimental study proposes to evaluate a group of 70 patients affected by hemifacial paralysis of level 3 to 6 on the House-Brackmann scale. 35 patients will be treated (Group A) with both OnabotulinumtoxinA and hyaluronic acid fillers with a monitored follow up. A control group of 35 patients (Group B) who will not be treated, will be enrolled to compare the efficacy of the treatment. During the study all the AE/ADR will be recorded.
Detailed Description
The patients will be evaluated with instrumental (3D pictures, neuro-physiological examination (EMG), radiological [Magnetic Resonance Imaging (MRI)], Cone Beam Computer Tomography (CBCT) and Ultrasound (US)) and non-instrumental analysis (clinical questionnaires and hystological analysis). The histology will be performed with both traditional and electronic approaches. The area of the biopsy will be the paralytic area in the two groups in order to study the soft tissue modulation of the injected molecules. Patient's qiality of life (QoL), through specifically test (FACE-Q), will be also evaluated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemifacial Paralysis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
monocenter, no treated controlled group, randomized clinical trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Hyaluronic Acid filler and Botulinum Toxin group
Arm Type
Experimental
Arm Description
Hyaluronic Acid filler: Juvederm Volbella: it will be used in the softer soft tissue, beacuse its reology is the softest Juvederm Volift: it will be used in malar area, because its reology is intermediate between the three products Juvederm Voluma: il will be used unstructured area bacause it has the best rheologic characteristics in the reintegration of loss of tissue. The differents products are going to use in different areas, depending on the area of the paralysis. Botulinum Toxin: Vistabex (50U/vial): it is going to be used in the controlateral area of the paralysed face, in order to relax muscle hyper-tonicity. Dosage and administration steps will be selected according to the clinical situation.
Arm Title
Control group
Arm Type
No Intervention
Arm Description
The control group will undergo at the same examinations of the treated group but it will not be subjected to any treatment.
Intervention Type
Device
Intervention Name(s)
Juvederm
Other Intervention Name(s)
Hyaluronic Acid
Intervention Description
Juvederm Volbella: 15mg/ml, it is injected 1.5ml per patient per treatment (a total of 3ml per patient split in 2 treatment sessions at a 4 months interval); Juvederm Volifit: 17.5mg/ml, it is injected 3ml per patient per treatment (a total of 6ml per patient split in 2 treatment sessions at a 4 months interval); Juvederm Voluma: 20mg/ml, it is injected 5ml per patient per treatment (a total of 10ml per patient split in 2 treatment sessions at a 4 months interval)
Intervention Type
Drug
Intervention Name(s)
Vistabex
Other Intervention Name(s)
Botulinum Toxin
Intervention Description
Vistabex: 50U/vial, it is injected up to 80U per patient per treatment (2 treatment sessions at a 4 months interval)
Primary Outcome Measure Information:
Title
House-Brackmann scale
Description
Change from baseline House-Brackmann score at day 270 will be assessed and then compared between the trial groups. The House-Brackmann score is a score to grade the degree of nerve damage in a facial nerve palsy. The measurement is determined by measuring the upwards (superior) movement of the mid-portion of the top of the eyebrow, and the outwards (lateral) movement of the angle of the mouth. Ti is consist of VI level: Grade I - Normal; Grade II - Slight Dysfunction; Grade III - Moderate Dysfunction; Grade IV - Moderate Severe Dysfunction; Grade V - Severe Dysfunction; Grade VI - Total Paralysis
Time Frame
Day 0 and day 270
Secondary Outcome Measure Information:
Title
Facial Appearance
Description
Facial Appearance will be assessed by FACE-Q Appearance scale measuring different concepts: Area Under Chin, Cheeks, Crows' Feet, Eyes, Forehead & Eyebrows,Lines Between Eyebrows, Lip Lines, Lower Eyelids, Marionette Line, Neck, Nostrils, Upper Eyelids, Cheekbones, Chin, Eyelashes, Face Overall, Forehead Lines, Lines Overall, Lips, Lower Face & Jawline, Nasolabial Folds, Nose, Skin. Each scale is composed of a series of items (or questions) that evaluate a concept of interest. Patient responses to items are on a four-point scale and are asked to answer with their face/facial appearance in mind. Answers for a scale are summed and converted to a score from 0 to 100. A higher score indicates a better outcome.
Time Frame
Day 0 and day 270.
Title
Health-Related Quality of Life
Description
Health-Related Quality of Life will be assessed by FACE-Q Quality of Life scale measuring different concepts: Age Visual Analogue (score ranging from -15 to +15), Aging Appraisal, Appearance-Related Distress, Early Life Impact of Treatment, Expectations, Psychological Function, Recovery Early Symptoms, Decision Satisfaction, Outcome Satisfaction,Social Function. Each scale is composed of a series of items (or questions) that evaluate a concept of interest. Patient responses to items are on a four-point scale. Answers for a scale are summed and converted to a score from 0 to 100. For most of these scales, a higher score indicates a better outcome.
Time Frame
Day 0 and day 270
Title
Adverse Effects
Description
Adverse Effects related to different parts of the face (Cheeks, Lower Face, Neck, Eyes, Forehead, Eyebrows, Scalp, Lips, Nose, Skin) will be assessed by FACE-Q Adverse Effects scales. Each scale is composed of a series of items (or questions) that evaluate a parts of the face. Patient responses to items are on a three/four-point scale. Answers for a scale are summed and converted to a score from 0 to 100. A higher score indicates a better outcome.
Time Frame
Day 0 and day 270
Title
Patients experience of care
Description
Patients experience of care related to satisfaction with information, medical team, office staff and with doctor/surgeon will be assessed by FACE-Q experience of care scales. Each scale is composed of a series of items (or questions) that evaluate the satisfaction. Patient responses to items are on a four-point scale. Answers for a scale are summed and converted to a score from 0 to 100. For all these scales, a higher score indicates a better outcome.
Time Frame
Day 0 and day 270
Title
Facial symmetry
Description
Facial symmetry will be performed through the analisys of 3D-photography implemented with a face grid, that allows the quantification of symmetry of the face. The face grid permits to calculate the distance in millimeters of two points from the midline (both in vertical and horizontal direction).
Time Frame
Day 0, day 20, day 150, day 270
Title
Facial aesthetic
Description
Facial aesthetic will be evaluated through the analysis of 3D-photography implemented with a face grid and the Arnett's aesthetic analysis, in order to appreciate the improvement of facial aesthetic.
Time Frame
Day 0 and day 270
Title
Facial aesthetic - thickness of soft tissue
Description
The thickness of soft tissue will be evaluated using MRI and US (millimetric quantification of the thickness of different areas)
Time Frame
Day 0 and day 270
Title
Facial aesthetic - thickness of hard tissue
Description
The thickness of hard tissue will be evaluated using CBCT (millimetric quantification of the thickness of the different areas)
Time Frame
Day 0 and day 270
Title
Facial aesthetic - tropism of muscles
Description
The tropism of muscles will be evaluated using US and cathegorized in atrophy, hypotrophy, eutrophy, hypertrophy.
Time Frame
Day 0 and day 270
Title
Facial aesthetic - patho-physiological condition
Description
The patho-physiological condition will be evaluated throught an histological analysis that provides a qualitative analysis of injected and not injected tissue and specifically the effects on the fiber muscles
Time Frame
Day 0 and day 270
Title
Hystological analysis
Description
% of patients with tissue changes assessed by hystological analysis using scanning electron microscope and/or transmission electron microscope provides a through examination of tissue changes due to the physical introduction of the products, comparing different conditions in injected and not-injected tissue and eventually any effect on the fiber muscles.
Time Frame
Day 0 and day 270
Title
EMG
Description
EMG provides eletric potentials of the facial neuromuscular complex in order to evaluate the activity and symmetry oh their function.
Time Frame
Day 0 and day 270
Title
Adverse Events
Description
Registration of number and type of adverse events
Time Frame
Day 0, day 20, day 30, day 140, day 150, day 270

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged > 18 years and < 65 years Hemifacial paralysis from 3 to 6 on the House-Brackmann scale Never treated with HA and BTX injection Signed informed consent Women of childbearing potential will only be included in the study if uptaking hightly effective birth control measures. Exclusion Criteria: Hypersensitivity to any component of the products used Diabetes, systemic disease, coronary artery disease, acute-chronic hepatitis C, autoimmune disease and/or other disease involving poor general health clotting problem. Peripheric neuro-musculars disorders, amyotrophic lateral sclerosis. Pregnant or lactating
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dario Bertossi, Prof
Phone
0458126768
Email
dario.bertossi@univr.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dario Bertossi, Prof
Organizational Affiliation
AOUI Verona
Official's Role
Principal Investigator
Facility Information:
Facility Name
Azienda Ospedaliera Universitaria Integrata
City
Verona
ZIP/Postal Code
37126
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dario Bertossi, Prof
Phone
0458126768
Email
dario.bertossi@univr.it

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Onabotulinumtoxin A and Hyaluronic Acid Fillers in the Treatment of Facial Paralysis

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