Clinical Assessment of Skin Quality and Efficacy of Dermal Line Improvement Following Four Bipolar Radiofrequency Microneedling Treatments
Phase: NA
Conditions: Aging
Sponsor: University of Texas Southwestern Medical Center

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Clinical Assessment of Skin Quality and Efficacy of 
Dermal Line Improvement Following Four Bipolar 
Radiofrequency Microneedling Treatments 
 
NCT 05085730 
Document Date: 11/17/2022 
 
 

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Clinical Assessment of Skin Quality and Efficacy of 
Dermal Line Improvement Following Four Bipolar 
Radiofrequency Microneedling Treatments 
 
 
 
 
 
SPONSOR 
InMode 
 
TESTING & AMINISTRATIVE 
FACILITY 
 
UT Southwestern Medical Center 
1801  Inwood Road 
Dallas, TX 75390-9132 
 
PRINCIPAL INVESTIGATOR 
 
Dr. Jeffrey Kenkel, MD 
 
SUB-INVESTIGATORS 
 
Dr. Abby Culver, MD 
Jasmine Panton, MBe 
 
 
1. Background 
 
The human skin aging process is characterized by thinning of the dermis, atrophy of the 
extracellular matrix, and reduced collagen synthesis[1]. Loss of collagen in the dermis is of 
aesthetic concern, as it is the main structural support in the dermis and its loss results in skin 
laxity. Photo-damaged skin, mostly due to UVR, causes degradation of elastic fibers, which is 
histologically seen as disorganized tangles of elastin. Additionally, as we age, skin tends to 
appear more dry due to its poor hydration and turgor capacity[1]. The use of minimally invasive 
aesthetic treatments in reducing signs of aging has been gaining in popularity over surgical 
treatments in recent years[2]. Several energy types including, laser, radiofrequency, infrared, 
and ultrasound, have been developed for facial rejuvenation[3]. These treatments induce 
controlled thermal damage to the dermis and cause collagen contraction and neocollagenesis 
resulting in skin tightening over several months[2]. The effects of facial rejuvenation treatments 
on collagen have been well defined in literature, however, the role of elastin in facial 
rejuvenation has not been well studied.  
 
In facial skin aging, the skin loses elasticity and begins to sag. Minimally invasive bipolar 
radiofrequency produces a controlled thermal injury in a fractional manner without damaging 
the dermal-epidermal junction, epidermis or subcutis[5]. Radiofrequency, unlike lasers, are 
chromophore-independent providing better penetration than lasers, and spare sweat glands, 
sebaceous glands, and hair follicles[5,6].  
 
The InMode Morpheus8 System is a bipolar fractional radiofrequency device which uses 
microneedles and thermal heat to stimulate neocollagenesis and neoelastogenesis.  
 

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This study intends to evaluate the safety and effectiveness of the InMode Morpheus8 System to 
treat skin on the lower face and assess its effect on skin quality and dermal lines.  This device 
has been FDA cleared for full body subdermal adipose tissue remodeling. 
 
There are alternative treatments that have demonstrated surface changes of the skin and 
improvement in dermal lines. We feel that the InMode Morpheus8 may be able to produce 
clinically significant improvement in the quality of facial and neck skin as well as fine lines and 
wrinkles in an office-based setting with limited downtime.  This device has been used in the 
Department of Plastic Surgery clinic off-label for the past six months for this purpose.  
Additionally, our research team conducted a study using Ulthera, an ultrasound device, 
approximately 10 years ago; the results of this study led to its FDA approval for the treatment 
of lax neck skin.  We are also finishing a study looking at another bipolar radiofrequency, 
microneedling device.  
 
2. Purpose 
 
The primary objective of this study is to evaluate the safety and efficacy of a bipolar fractional 
radiofrequency treatment via use of the InMode Morpheus8 System to achieve skin texture and 
quality change and to treat facial fine lines and wrinkles of the lower face.  
 
3. Study Design 
 
This is a single center, unblinded, non-randomized, non-controlled study designed to follow a 
total of up to thirteen (13) qualified and consenting subjects receiving 4 bipolar fractional 
radiofrequency microneedling treatment of the lower face, once every 4-6 weeks for a total of 
4 treatments, under an IRB approved protocol. Following these treatments, patients will have 
follow-up visits at 3-months, and 6-months post-treatment.  The effects of bipolar fractional 
radiofrequency treatments via the InMode Morpheus8 System will be determined by subjective 
and objective analysis through clinician and subject assessments.  
 
Overall assessment of clinical outcome and safety will be based on clinic visits and evaluation of 
pre- and post-procedural photos. These photos will be identifiable full face photos, and subjects 
will be adequately informed of such. One unblinded clinician’s assessments of satisfaction will 
be characterized using the Lemperle Wrinkle Assessment Scale, a four-point Allergan skin fine 
line scale and a four-point Allergan Skin Roughness scale at baseline, 3 month follow up and 6 
month follow up visits. The five-point Global Aesthetic Improvement Scale (GAIS) will also be 
used at 3 month and 6 month follow up visits. Additionally, evaluation of pre- and post- 
procedural photos will be performed comparing baseline and follow ups by blinded raters. In 
conjunction with standard and close-up photography, subjects will also have photos taken using 
the VISIA Imaging system and will undergo high-resolution ultrasonography, transepidermal 
water loss (TEWL) measurements and/or BTC 2000 measurements for exploratory purposes. 
High-resolution ultrasound will be utilized for assessment of skin thickness and density. TEWL 
measurements are taken via the Bio Aquaflux and will be used to evaluate barrier function of 
the skin epidermal layer to determine progress of epidermal healing after treatment and BTC 

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2000 will be used to measure skin laxity, viscoelastic deformation, stiffness, energy absorption, 
elasticity and deformation values of skin. Additionally consenting subjects will undergo skin 
biopsies at the treatment site to better qualify the measurements and results from the items 
mentioned above. Micro-biopsies using 0.33mm size punches will be used to extract core 
tissues pre- and post-treatment for histological evaluation (tissue structure, elastin, collagen 
and hyaluronic acid expression) and gene expression assessment (elastin, other major ECM 
molecules and elastin related genes). 
 
From these exploratory procedures the improvement in skin quality and dermal lines of the 
lower face and jawline can be evaluated in comparison to pre-treatment assessments. 
 
4. Study Population 
 
This is a single-site study at UT Southwestern Medical Center at Dallas in the Department of 
Plastic Surgery. Up to thirteen (13) subjects will be enrolled and treated.  
 
4.1. Subject Enrollment 
Subjects who are interested in treatment for facial fine lines and wrinkles will be recruited 
for the study. Prospective patients will be screened to check if they are acceptable 
candidates. Subjects meeting eligibility requirements will be scheduled for an official 
screening visit. Additionally, if subjects express an interest in the procedure during a clinic 
appointment with Dr. Kenkel or Dr. Culver, he or she may discuss the study with them and 
assess the treatment area.  If a subject is deemed a good candidate, Dr. Kenkel or Dr. Culver 
will connect the patient with a research coordinator or delegated member of their research 
team to answer any further questions. Potential subjects will have the study explained to 
them, will be asked about their willingness to be involved in the study, and their willingness 
to sign an informed consent form. Included in this interview will be questioning from the 
investigator or staff member about any privacy concerns the individual may have. 
 
4.2. Informed Consent Form 
An IRB-approved informed consent form (ICF), explaining the purpose, design, risks and 
duration of the study, will be given to each candidate subject before participation in any study 
procedures.  The candidate subject will be given as much time as needed to read the ICF and 
will have the opportunity to have any study-related questions answered to their satisfaction 
prior to signing the ICF.  An original signed copy for each subject participating in the study will 
be retained in the study file and each subject will receive a signed copy.  By signing the 
consent form, subjects indicate that they are willing to have their full-face photograph and 
acknowledge that these photos may be used for scientific publication. If the subjects decline 
permission to be photographed, they may not participate in the study since the photographic 
documentation of treatment outcome is an important measure of evaluation. The candidate 
subject will be ineligible to participate in this study without a signed ICF.   
 
5. Eligibility Criteria 
 

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5.1. Inclusion Criteria  
1 
Healthy male and female adults between ages 21-70 years of age. 
2 
Presence of facial dermal lines and skin changes of the lower face associated with 
age or environmental exposure. 
3 
Subjects who can read, understand, and sign the Informed Consent Form. 
4 
Subjects willing and able to comply with all study requirements. 
5 
Fitzpatrick skin type I-VI. 
6 
Minimum of 1 on the Lemperle Wrinkle Assessment Scale, Allergan Fine Line Scale 
and Allergan Skin Roughness Scale 
7 
Subject is willing not to undergo any type of aesthetic procedure that could 
confound the study device treatment effects until he/she completes the study. 
 
5.2. Exclusion Criteria: 
1 
Active localized or systemic infections, that may alter wound healing. 
2 
Immunocompromised subjects. 
3 
Subjects with coagulation disorder. 
4 
History of skin photosensitivity disorders, or use of photosensitizing 
drugs (e.g., tetracycline or sulfa drugs). 
5 
Pregnant and/or lactating (All female volunteers will be advised 
about using birth control during the period of study). 
6 
5 on the Lemperle Wrinkle Assessment Scale or 4 on the Allergan Fine 
Line Scale and/or Allergan Skin Roughness Scales 
7 
Scarring in areas to be treated. 
8 
Tattoos in the treatment areas to be treated. 
9 
Significant open facial wounds or lesions. 
10 
Severe or cystic acne in treatment areas. 
11 
Current active smoker. 
12 
Use of Accutane (Isotretinoin) within the past 6 months. 
13 
Use of topical retinoids within 48 hours. 
14 
Use of prescription anticoagulants. 
15 
Pacemaker or internal defibrillator. 
16 
History of skin disorders resulting in abnormal wound healing (i.e. 
keloids, extreme dry and fragile skin). 
17 
Subjects on current oral corticosteroid therapy or within the past 6 
months 
18 
Metal implants in the treatment area. 
19 
In the opinion of the investigator, subject is unwilling or unable to 
adhere to all study requirements, including application and follow-up 
visits. 
20 
Subjects with a history of radiation therapy to the treatment area. 
21 
Subject has a history of allergy to lidocaine or ester-based local 
anesthetics. 
22 
Subjects with significant cardiac history or rhythm disturbance who 
may be unable to tolerate lidocaine with epinephrine. 

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23 
Subjects with any skin pathology or condition in the treatment area 
that could interfere with evaluation or with the use of typical ancillary 
medical treatments or care used before, during or after treatments 
(e.g. psoriasis, rosacea, eczema, seborrheic dermatitis, vitiligo, hyper 
or hypo-skin pigmentation conditions such as post inflammatory 
hyperpigmentation). 
24 
Subjects who are unwilling to shave excessive hair in the treatment 
area that might influence or impair evaluation in the opinion of the 
Investigator. 
25 
Subjects have undergone skin resurfacing or tightening treatments in 
the treatment area over the past year. 
26 
Subjects have undergone dermatological treatments such as fillers 
and neurotoxins for the past 6 months in the treatment area. 
27 
Subjects have undergone laser and light treatments in the treatment 
area over the past 3 months. 
28 
Subjects who have undergone surgery in the proposed treatment 
area within the past 3 months. 
29 
Subjects have undergone superficial peel or microdermabrasion 
within 4 weeks. 
 
6. Study Endpoints 
6.1. Primary Endpoints 
1 
Improvement of fine lines and wrinkle severity using a modified 
Lemperle Wrinkle Assessment Scale, the Allergan Scale for Fine Lines 
and the Allergan Skin Roughness Scale Assessment at baseline, 3-
months, and 6-months post-treatment 
2 
Clinician’s Global Aesthetic Improvement Scale (CGAIS) at 3-months 
and 6-months post-treatment  
6.2. Secondary Endpoints 
1 
Monitoring of adverse events throughout the course of the study. 
2 
Subject Global Aesthetic Improvement Scale (SGAIS) at 3-months and 
6-months post-treatment  
3 
Patient Satisfaction Questionnaire at 3-months and 6-months post-
treatment 
4 
Exploratory skin measurements using high resolution ultrasound, 
TEWL measurements (Bio Aquaflux) and BCT 2000 to assess skin 
thickness, density, firmness as well as the integrity of the stratum 
corneum 
5 
Micro-biopsies for histological evaluation (tissue structure, elastin, 
collagen and hyaluronic acid expression) and gene expression 
assessment (elastin, other major ECM molecules and elastin related 
genes) 
 
7. Safety Endpoint 

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Safety will be determined based on adverse event data collected from both the 
Morpheus8 treatment visits and all follow-up evaluations of the treated areas.  
The Primary Safety Endpoint will be the incidence rate, severity, and relatedness 
of adverse events observed in the study.  All adverse events that arise during the 
course of the study will be recorded and summarized in the final study report. 
 
8. Study Visit Procedures 
 
8.1. Screening Visit: Visit 1 
The purpose of the study, eligibility criteria and potential risks will be discussed with the 
potential study subject.  All interested subjects will be given the Informed Consent Form 
with adequate time for review. The Investigator and/or designee will address questions and 
concerns raised by the subject. Those subjects who elect to participate, will sign the 
Consent Forms prior to any study procedures. 
 
Subjects will be screened to ensure that they meet all study criteria.  The following 
enrollment and screening activities will be performed: 
1. Discuss the bipolar fractional radiofrequency device with each subject presenting for 
treatment 
2. Obtain informed consent and HIPAA authorization 
3. Collect any appropriate medical and surgical history including current medications, 
skin type, recent sun exposure, allergies, major illnesses, etc. 
4. Evaluation of pre-existing skin conditions that may have potential study impact  
5. Urine pregnancy test for women of childbearing potential 
6. Examination of the treatment area by the physician 
7. Mapping of the location and approximate area of treatment site(s)  
 
This visit will take about 1 hour. 
 
8.2. Treatment Visits: Visit 2-5  
The first Treatment Visit (Visit 2) activities may be combined with the Screening Visit (Visit 
1).   
 
A member of the study team will ask subjects if they experiences any change in their health 
since their previous visit. If an adverse event (AE) is reported then the Investigator or 
designated clinician will be informed and an AE form will be completed for their review. 
 
The following activities will be completed before the first treatment for research purposes: 
1. Obtain close up and standard photography 
2. Obtain surface area assessments via the Vectra H2 3D Imaging System and Standup 
Vectra 
3. Assess skin using multiple established objective scales including the Lemperle 
Wrinkle Assessment, Allergan Fine Line and Allergan Skin Roughness Scales. 

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4. Obtain high-resolution ultrasound images, TEWL measurements (Bio Aquaflux) and 
BTC 2000 images. 
5. Collect two 0.33mm biopsies using WellTech Rapid-Core 0.33mm Biopsy Punch pre-
treatment. The biopsies will be taken from the cheek adjacent to the nasolabial fold 
within the designated area for treatment. One biopsy will be used for histological 
studies and the other for gene expression studies 
a. Biopsies will only be taken at the first Treatment Visit, no others, to be used 
for baseline measurements. 
 
The procedure will be performed in our clinic following standard of care procedures. After 
allowing 10 minutes for the anesthetic to take effect, the skin will be cleansed and prepped 
with an antiseptic. A trained staff member will apply a topical anesthetic (benzocaine, 
lidocaine, tetracaine) and shortly thereafter a local anesthetic (1% xylocaine with 
epinephrine or equivalent) will be injected for additional pain control. The treatment 
parameters will be determined by the treating physician and will be based on the patients’ 
skin texture, thickness, and lines. In general, the skin of the lower face will be treated at 
several depths, with two successive passes per depth, ranging from 1-4 mm. In most areas 
all four depths will be used except when the skin is thin where depths of 1-3 mm will be 
utilized. In most cases a 12- and 24-point tip will be utilized and then followed by the use of 
the resurfacing tip.  Energy settings will be chosen by the treating physician based on the 
patients’ skin texture, thickness, and lines. The settings will range from 20-40.   
 
 
The following activities will be performed on all subjects: 
 
1. The study treatment (bipolar fractional radiofrequency) per study treatment 
guidelines provided 
2. Review of post treatment expectation and management for the treatment as 
detailed in the study device instruction for use (IFU) 
3. All expected (e.g., edema, erythema) and unexpected (e.g., burn, blister) 
treatment adverse events will be documented and graded  
 
 
 
 
Post-treatment Care and Precautions 
 
Appropriate post-treatment care instructions will be provided as deemed appropriate 
by the Investigator or study staff. Post treatment assessment will be performed.  
Subjects will be instructed that blistering, bleeding, oozing, strong pain, swelling 
persisting for more than 72 hours, or signs of infection (e.g., pus, drainage, fever) are 
cause for immediate concern and they should contact the investigator and/or his 
designee, to be evaluated.  Downtime after treatment typically can last approximately 
0-2 days. 
 
This visit will take about 1 hour. 
 
 

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8.4 Follow-Up Visits (Visits 6 and 7) 
At a minimum, all subjects will return for follow-up at 3 months (+/- 7 days) and 6 months 
(+/- 7 days) after treatment.   
 
The following activities will be performed on all subjects during the follow-up visits:  
 
1. The physician or study staff will perform an examination of the skin of the 
treatment area.  
2. All expected (e.g., edema, erythema) and unexpected (e.g., burn, blister) 
treatment local skin responses will be documented and graded at every visit 
3. Adverse Event Review 
4. Query the subject regarding any change in health since enrollment into the study 
5. Perform a detailed cutaneous exam of the treatment area, review and record 
any local adverse events related to cutaneous changes 
6. Collect an updated surgical history and record any change in concomitant 
medications or treatments. 
7. Obtain close-up and standard photography 
8. Obtain surface area assessments via the Vectra H2 3D Imaging System and 
Standup Vectra 
9. Assess skin using multiple established objective scales including the Lemperle 
Wrinkle Assessment, Allergan Fine Line and Allergan Skin Roughness Scales. 
10. Assess skin using both Clinician and Subject Global Aesthetic Improvement Scales 
(GAIS) 
11. Assess patient satisfaction using the Patient Satisfaction Questionnaire 
12. Obtain post-treatment high-resolution ultrasound images, TEWL measurements 
(Bio Aquaflux) and BTC 2000 images 
a. Noninvasive skin measurements will be obtained at each Follow-up Visit 
(#6-7) 
13. Collect two 0.33mm biopsies using WellTech Rapid-Core 0.33mm Biopsy Punch 
post-treatment. The biopsy will be taken from the cheek adjacent to the 
nasolabial fold within the designated area for treatment. One biopsy will be used 
for histological studies and the other for gene expression studies 
a. Biopsies will be obtained at each Follow-up Visit (#6-7) 
14. Other assessments may be conducted per the clinical sites standard practice, 
such as collection of vital signs. 
 
 
These visits will take about 1 hour. 
 
8.5 Additional Unexpected Follow-up Visits 
If a potential adverse event is reported by the subject or identified during examination, the 
Investigator or study staff will schedule the subject for an Event Follow-up Visit within 24 
hours.  At this visit the Investigator or his designee will: 
 

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1. Obtain a complete history of the event in question as well as conduct an 
examination of the subject and determine if the reported event qualifies as an 
Adverse Event.  If the event is determined to be an Adverse Event, an Adverse 
Event (AE) case report form and Event Follow-up (EF) Visit case report form must 
be completed.  One AE case report form should be used to track the history of an 
individual AE throughout the period of the study.   
2. Collect an updated medical and surgical history along with recording of 
concomitant medications or treatments. 
3. Take photographs of the subject with attention to the area in question. 
4. Render treatment for the event, if any, as determined by the medical judgment 
of the investigator. 
 
Additional follow-up visits may also be required after the last scheduled visit to assess 
resolution of adverse events. 
 
9. Subject Instructions 
 
Subjects will be provided with the following instructions to follow during the study:   
 
9.1. Washout Period and/or Pre-Study Instructions 
No topical medications or topical retinoids 2 weeks prior to visit 1  
 
9.2. Subject Instructions for Study Visits 
1 
Subjects will be encouraged to consistently use a face wash, moisturizer, and 
sunscreen of their choosing. Apply the face wash to the entire face and neck every 
morning, as well as the facial moisturizer. Sunscreen is recommended to be applied 
each morning and prior to any sun exposure.  
2 
Remove all makeup at least 30 minutes prior to each scheduled clinic visit using 
facewash. No other topical products should be applied to the face, neck or eye 
area until the study visit has been completed.  If a subject arrives having not 
removed all makeup, he/she will be required to remove the residual makeup at the 
clinic and wait at least 20 minutes prior to procedures.  
 
9.3. General Study Instructions  
1 
Avoid extended periods of sun exposure and all use of tanning beds for the 
duration of the study. Extra care should be taken to wear protective clothing, 
including sunglasses, and avoid sun exposure from 10 AM to 4 PM.  
2 Continue use of all regular brands of color cosmetics, makeup remover, and skin 
cleansers for the duration of the study. Individuals must refrain from using any 
anti-aging, acne, and acne scar products or devices and beginning the use of any 
new facial products or devices other than the assigned test material. Use of 
moisturizing foundation will be acceptable as long as the subject has a history of 
safe usage of the foundation. 

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3 Subjects should abstain from undergoing any dermatological treatments during the 
entire study duration. 
 
10. Schedule of Events 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
(Month 3) 
Visit 7 
(Month 6) 
 
Procedures 
Screening# 
Treatment 
1# 
Treatment 
2 
Treatment 
3 
Treatment 
4 
Follow Up 
1 
Follow Up 
2 
Informed Consent 
X 
 
 
 
 
 
 
Eligibility Criteria 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical History/ Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
Physical Exam  
X 
 
 
 
 
 
 
Urine Pregnancy  
X 
 
 
 
 
 
 
 
InMode Treatment 
 
X 
X 
X 
X 
 
 
Standard Photographs 
 
X 
 
 
 
X 
X 
Surface area assessment 
using H2 3D Imaging and 
Standup Vectra 
 
X 
 
 
 
X 
X 
CGAIS/SGAIS 
 
 
 
 
 
 
 
 
X 
X 
Patient Satisfaction 
Questionnaire  
 
 
 
 
 
X 
X 
Objective Assessments^ 
 
X 
 
 
 
X 
X 
Non-invasive Skin Tests*  
 
X 
 
 
 
X 
X 
Biopsy 
 
X 
 
 
 
X 
X 
Safety Assessment 
 
X 
X 
X 
X 
X 
X 
Blinded Evaluations 
 
 
 
 
 
 
X 
 
 
# Treatment visit activities may be conducted at the Screening Visit 
^ Lemperle Wrinkle Assessment Scale, Allergan Fine Line Scale, Allergan Skin Roughness Scale 
* TEWL measurement, BTC-2000, and/or high frequency ultrasound images will be taken  
 
11. Assessments 
Note that the order of the assessments listed below may be altered from the order indicated in 
the study visits in order to help study flow, or at the recommendations of the Sponsor or 
Investigator. Any change in the order of procedures will not compromise study data. 
11.1. 
Assessment of Facial Wrinkling 
Assessment of facial wrinkling will be performed at baseline and at 3-months and 6-months 
post-treatment. Facial wrinkling will be assessed using the Lemperle Wrinkle Assessment 
Scale9. Wrinkling in the following regions- forehead, glabellar folds, periorbital, preauricular 
areas, cheek, nasolabial folds, upper lip, marionette lines, corners of mouth, chin, and neck- 
can be assessed according to scale’s definitions (See Appendix I). 
 

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11.2. 
Assessment of Fine Lines 
Assessment of fine lines will be performed at baseline and at 3-months and 6-months post-
treatment. Fine lines will be assessed using the Allergan Fine Line Scales for Facial Fine Lines 
11. Fine lines on the midface/cheeks will be assessed according to the scale’s definitions (See 
Appendix IIa and IIb). 
 
11.3. 
Allergan Skin Roughness Scale  
Assessment of skin roughness will be performed at baseline and at 3-months and 6-months 
post-treatment. Skin roughness will be assessed using the Allergan Skin Roughness Scale13. 
Skin roughness will be assessed according to the scale’s definitions based on descriptions of 
severity of skin coarseness, crosshatching and elastosis in the midface area (See Appendix 
IIIa and IIIb). 
 
11.4. 
Clinician’s Global Aesthetic Improvement Scale (CGAIS) 
Subjective assessment of aesthetic improvement will be performed at 3-months and 6-
months post-treatment (See Appendix IV).  
The scale should be completed in two steps: 
1 
Based on a live assessment of the subject while referring to the subject’s pre-
treatment photographs of the face and neck, and 
2 
Based on a comparison of the subject’s pre-treatment photographs to the current 
post-treatment photographs of the face and neck. 
 
11.5. 
Subject’s Global Aesthetic Improvement Scale (SGAIS) 
Subjective assessment of aesthetic improvement will be performed at 3-months and 6-
months post-treatment (See Appendix IV).  
 
11.6. 
Patient Satisfaction Questionnaire 
Subjective assessment of patient satisfaction will be performed at 3-months and 6-months 
post-treatment (See Appendix V). 
 
11.7. 
Imaging Procedures 
Prior to photography procedures, clinic personnel will ensure that subjects have a clean face 
and neck with no makeup as described in the study procedures. Subjects will remove any 
jewelry from the area(s) to be photographed and equilibrate for at least 15 minutes to 
ambient conditions within the clinic before any photographs are taken. Subjects will be 
provided with a headband or hair tie to keep hair away from the face.  
 

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Subjects will be instructed to adopt neutral, non-smiling expressions with their eyes gently 
closed for VISIA. Subjects will be carefully positioned for each photograph, directly facing 
the camera for the center view and turned at a 45° angle for the right and left side views. 
1 
VISIA Complexion Analysis 
Digital images will be taken of each applicable subject with fine lines and wrinkles 
on the face using the VISIA Complexion Analysis System at baseline, 3-months 
post-treatment, and 6-months post-treatment. Each subject will have a total of 3 
full-face images taken (right side, left side, and center view) using the following 
lighting conditions: 
Standard lighting 1: visible (bright) 
Standard lighting 2: visible (flat) 
Cross-polarized: 
UV-NF 
2 
NIKON D7100 
Standard, close-up and cross-polarized photography of the face and neck will be 
utilized for evaluation of fine lines and wrinkles. These photographs will be taken 
utilizing the Nikon D7100 at baseline, 3-months post-treatment, and 6-months 
post-treatment. 
 
11.8. 
Noninvasive Procedures 
Biox Aquaflux will be used to measure transepidermal water loss (TEWL) measurements 
which evaluate barrier function of the skin epidermal layer to determine progress of 
epidermal healing after treatment. The BTC 2000 will be used to measure skin laxity, 
viscoelastic deformation, stiffness, energy absorption, elasticity, and deformation values of 
skin.  All procedures will be performed on the submental area.  
 
11.9. 
Skin Biopsies 
Two 0.33 mm punch biopsies will be taken from the cheek adjacent to the lateral upper lip 
at Visit 2, Visit 6 and Visit 7. Prior to biopsy the area will be cleaned with alcohol and a local 
numbing agent, 0.5%-1% Lidocaine with epinephrine, will be used to anesthetize the area 
being biopsied. If bleeding is present, pressure will be held on the biopsy site until bleeding 
stops.  Immediately after collection, biopsies for histology and gene expression will be put in 
4% PFA and RNA-Later solution, respectively. Biopsies will be stored in a cooler for transfer 
to the Plastic Surgery Research Lab at UTSW for molecular analysis. 
 
11.10. 
Blinded Evaluation 
Blinded evaluation will be performed by three qualified, non-treating clinicians to 
determine if the InMode Morpheus8 System is effective in improving the appearance of 
facial and neck skin quality and dermal lines. 
 
At study conclusion, the Principal Investigator will select three blinded, physician evaluators 
to assess photos of subjects taken pre- and post-treatment. The evaluators will be trained 

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by the PI or research team member on the grading scales in order to independently review 
photographs for each subject. The evaluators will be blinded to subject information and will 
only know that the study consisted of multiple treatment visits and follow up visits at 3 
months and 6 months. They will be provided a set of photos taken at three different visits – 
pre-treatment, 3 month post-treatment and 6 month post-treatment – in a randomized and 
unidentifiable order. No information will be provided that may allow them to determine the 
baseline from follow up imaging. Evaluators will be asked to assess the sets of pictures using 
the Lemperle Wrinkle, Allergan Fine Lines and Allergan Skin Roughness scales. After 
completion of the scales, the raters will be unblinded and asked to complete the Clinical 
Global Aesthetics Improved Scale (CGAIS). 
 
The source documents will be prepared and distributed to the blinded evaluators by a 
member of the study staff.  A decreased score for each assessment will indicate an 
improvement for the indicated parameters.  
 
12. Statistical Methods of Analysis 
This initial study will include change from baseline analysis.  
 
The primary outcome measure of effectiveness will be a paired comparison of baseline to all 
applicable post-baseline time points using data obtained from transepidermal water loss 
assessments, high resolution ultrasonography, BTC 2000 measurements, biopsy results, and 3D 
imaging results.  Photographs and 3D video of treated skin at follow-up visits will be compared 
to baseline for blinded scoring evaluations.  Mean of the change from baseline (defined as post-
baseline value minus baseline value) will be estimated at post-baseline time points for 
applicable parameters. 
 
The following will be calculated and reported for each evaluation parameter at the applicable 
post-baseline time point(s): 
Percent mean change from 
baseline =  
(visit mean score – baseline mean score) 
x 100 
baseline mean score 
 
For Clinician’s Global Aesthetic Improvement Assessment, the null hypothesis that the mean 
score is equal to 4 (no change) will be tested.  
 
13. Non-Significant Risk Determination 
In accordance with the definition of “Significant Risk Device” provided in the U.S. Code of 
Federal Regulations 21 CFR 812.3, the study device to be used in this research study has been 
determined to be a Non-Significant Risk (NSR) device based on the following: 
a)  It is not an implant 

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b)  It is not purported or represented to be for use in supporting or sustaining human 
life and do not present a potential for serious risk to the health, safety or welfare of 
a subject 
c)  It is not for a use of substantial importance in diagnosing, curing, mitigating, or  
     treating disease or otherwise preventing impairment of human health 
d)  Use of the device poses no risk to the health, safety, or welfare of a subject 
 
14. Device Description 
The InMode Morpheus8 System is a minimally invasive bipolar radiofrequency (RF) 
microneedling device FDA-cleared for full-body adipose tissue remodeling.  The fractional RF 
device, with adjustable penetration depth and energy delivery, contains 12-24 coated needles.  
During treatment, these needles penetrate and deliver thermal energy into the subdermal 
tissue, leading to coagulation of fat and contraction of the reticular dermis and surrounding 
connective tissue.  Additionally, it is theorized that the thermal injury caused by the RF energy 
initiates the wound healing process, stimulating neocollagenesis, elastogenesis, and 
angiogenesis.  
 
Image 1. InMode Morpheus8 System 
 
 

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Image 2. Morpheus8 Radiofrequency Microneedling Device
 
 
Image 3. Illustration of RF Microneedling Depth and Effect 
 
 
15. Potential Risks 
Blistering, burning, and infection: (Rare)  
A crust, blister or superficial wound can occur at the treatment area.  The risk of 
infection will be minimized by proper wound care. 
 
Bruising: (Rare)  
A mild bruising may occur at the treatment area as a result of radiofrequency 
exposure. This is usually transient and resolves in a few hours to few days. 
 
Transient edema and/or erythema: (Occasionally)  

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May develop within the irradiated areas but are usually temporary and fade within 
24-72 hours.  
  
Pigmentary changes: (Rare)  
Radiofrequency exposure can cause pigmentary changes such as hyper- (and 
hypopigmentation. Although this is usually temporary, it may be permanent on 
rare occasions. Sun avoidance and/or the use of a total sun block (SPF 30 or higher) 
will help minimize the intensity and duration of any pigmentary changes. 
 
Scarring: (Rare)  
As with any form of energy exposure, there is a small risk of scarring. However, 
this is minimized by proper technique and wound care. 
 
Allergic Reaction: (Rare)  
There is a possibility of an allergic or toxic reaction to anesthesia used to numb 
the areas. Subjects will be questioned with regard to any history of allergies and 
carefully monitored for signs of allergic reaction. 
 
Biopsy 
Risks associated with biopsy include: 1) scarring - a small risk of scarring, which can be 
mitigated by proper technique and wound care; 2) allergic reaction - there is a possibility of an 
allergic or toxic reaction to anesthesia used to numb the areas. Subjects will be questioned with 
regard to any history of allergies and carefully monitored for signs of allergic reaction. 
 
Photography 
The subject may be uncomfortable with sitting still for an extended period of 
time or from turning his/her body in various positions. Subjects may be sensitive 
to the bright and repeating flashes from the camera, which can sometimes cause 
headaches, irritation of the eyes, discomfort, aftereffects such as seeing spots, 
and in rare cases, could stimulate a migraine headache or epileptic seizure. 
 
Photographs include a risk of identification, as these will be full face photos. 
Privacy will be protected to the greatest extent possible. Photos will only be 
identified by a unique subject identification number that contains no personal 
identifying information. All photos will be stored on a password secure drive, 
with only access by research personnel. For research purposes, photos may be 
used in scientific publications. 
 
Noninvasive procedures (exploratory) 
1. Biox Aquaflux will be used to measure transepidermal water loss (TEWL) 
measurements which evaluate barrier function of the skin epidermal layer 
to determine progress of epidermal healing after treatment. The standard 
time for TEWL measurements should take approximately 5 minutes.  
 

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2. The BTC 2000 will be used to measure skin laxity, viscoelastic deformation, 
stiffness, energy absorption, elasticity, and deformation values of skin. The 
standard time for BTC 2000 should take approximately 5 minutes.   
 
3. The DUB Skin Scanner, a high-resolution ultrasound, will be used to assess 
skin thickness, epidermal thickness, and skin density. The standard time 
for DUB should take approximately 5 minutes. 
 
All these tests are considered noninvasive, and no risks are anticipated. 
 
16. Potential Benefits 
Subjects may benefit by having an overall improvement in quality and texture of the skin as well 
as the presence of dermal lines of the lower face. There may be a benefit to the medical 
community by demonstrating the safety and effectiveness of a new technology in the 
management of skin quality of the lower face and jawline as well in the treatment of dermal 
lines.  This technology may have advantages over existing technologies currently in use (lasers, 
ultrasound, etc.) because of its combination of bipolar fractional radiofrequency and 
microneedling technology. This technology may lead to better clinical outcomes for an 
understudied area. 
 
17. Adverse Events 
17.1. 
Definitions 
Adverse Event 
An adverse event is any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in subjects, users or 
other persons, whether or not related to the investigational medical device. 
Unanticipated Adverse Device Effect 
An unanticipated adverse device effect (UADE) is any serious adverse effect (defined 
below) on health or safety, any life-threatening problem or death caused by, or 
associated with a device, if that effect, problem, or death was not previously identified 
in nature, severity, or degree of incidence in the protocol; or any other unanticipated 
serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects. 
 
A serious adverse event (SAE) is any adverse event that: 
a) led to death, 
b) resulted in life-threatening illness or injury 
c) resulted in permanent impairment of a body structure or body function 
d) resulted in in hospitalization or prolongation of existing hospitalization, 
e)   resulted in medical or surgical intervention to prevent permanent impairment to 
body structure or body function, or 

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f) led to fetal distress, fetal death, congenital abnormality, or birth defect 
 
17.2. 
Reporting 
Adverse events, and unanticipated adverse device effects (UADE) are collected from the 
time of subject consent until the subject exits the study. A description of the adverse event 
or device event, date of onset, severity, action taken, relationship to study treatment and 
outcome are documented in the case report form.   
 
The Investigator will submit to the reviewing IRB a report of any unanticipated adverse 
device effect (UADE)) as soon as possible, but in no event later than 10 working days after 
the investigator first learns of the event (CFR 812.150(a)(1)). 
 
18. Subject Safety and Data Monitoring 
For this protocol, which involves the use of a non-significant risk device, the Investigator will be 
responsible for the conduct of the study including accrual, subject experience, attrition, 
patterns of expected adverse events and/or unexpected adverse events, any protocol 
deviations or violations, and any changes in the risk/benefit analysis.   
 
Subjects will be asked about any adverse events throughout the study by the study staff. 
Subjects will be asked to contact the study staff if adverse events develop between visits.  An 
unscheduled visit will be arranged so that the Investigator can clinically evaluate and 
photograph these findings. All subjects will be discontinued from the study if their problem 
remains unchanged/becomes worse. The Investigator can decide to stop the study if he/she 
believes that the participants’ participation is no longer safe or if another treatment may be 
more helpful. The IRB or FDA may stop the research for the safety of the participants.  These 
adverse events will be documented and reported as required for compliance with applicable 
regulations.   
 
All study records and information will be identified by the subject number. All subject 
identifiers will be removed from all documents. The link between subject name and study ID 
number will be kept in separate password-protected files at the study site. Documents 
containing identifying information will be kept in locked files in the research staff’s locked 
office. All electronic study data will be password protected with access limited to members of 
the research team. No direct identifying information will be shared with any outside entities, 
unless required by regulatory agencies (FDA and IRB).  Electronic data (electronic data entry - 
Case Report Forms), if used, will be password protected.   
 
Photographs of the subject’s face will be taken at Enrollment/Treatment and Follow-Up  
visits. These photographs will be identified by subject numbers. Subject confidentiality will be 
protected to the greatest extent possible.  Quantitative surface area assessments will be done 
on lateral 3D images taken at baseline and compared with 3D images obtained at all follow-up 
visits.  
 

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This study will be performed in accordance with Health Insurance Portability and Accountability 
Act. These guidelines will be followed specifically with regards to the privacy and confidentiality 
of subject care and study records.  Personnel associated with Investigator’s office and the 
governing Institutional Review Board, have the right to review the data, including photographs, 
collected during this study.   
 
19. Protocol Deviations 
Emergency deviations (deviations necessary to avoid immediate apparent harm or protect life 
or physical well-being of subjects or others) and major deviations as defined by the reviewing 
IRB will be reported to the IRB within 5 working days of occurrence. All deviations will be 
tracked and summarized in the progress report for the next continuing IRB review.  
 
20. Sources of Research Material  
Demographics and medical history will include age, gender, weight, height, BMI, skin type, 
recent sun exposure, allergies, current medications, major illnesses, photographs, adverse 
events and treatment. Additionally, ultrasound images, TEWL measurements, OTC images, BTC 
2000 measurements, and biopsies will be obtained. 
 
High resolution ultrasound will be used to assess skin thickness and density. The standard time 
for use of high-resolution ultrasound should take approximately 5 minutes. Transepidermal 
water loss (TEWL) measurements will be used to evaluate barrier function of the skin epidermal 
layer to determine progress of epidermal healing after treatment. The standard time for TEWL 
measurements should take approximately 5 minutes. The BTC 2000 will be used to measure 
skin laxity, viscoelastic deformation, stiffness, energy absorption, elasticity, and deformation 
values of skin. The standard time for BTC 2000 should take approximately 5 minutes. 
 
Biopsies will be taken using 0.33mm biopsy punches of the submental area. Biopsies will allow 
investigators to correlate changes seen in skin measurements with histology and gene 
expression. Time for two biopsies will take approximately five minutes. Biopsies for histology 
will be fixed immediately after collection in 4% PFA followed by paraffin embedding. Biopsies 
for gene expression will be put in RNA-Later solution and transferred to the Plastic Surgery 
Research Lab for gene expression analysis. Whole genome sequencing will not be performed, 
we will only be analyzing proteins and RNA expression related to collagen, elastin, and the 
extracellular matrix production.  
 
21. References 
 
1. Tobin DJ. Introduction to skin aging. J Tissue Viability. Feb 2017;26(1):37-46. 
2. Hantash BM, Ubeid AA, Chang H, Kafi R, Renton B. Bipolar fractional radiofrequency 
treatment induces neoelastogenesis and neocollagenesis. Lasers Surg Med. Jan 
2009;41(1):1-9. 

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3. Alster TS, Tanzi EL. Noninvasive lifting of arm, thigh, and knee skin with transcutaneous 
intense focused ultrasound. Dermatol Surg. May 2012;38(5):754-759. 
4. Gold MH, Sensing W, Biron J. Use of micro-focused ultrasound with visualization to lift 
and tighten lax knee skin (1.). J Cosmet Laser Ther. Oct 2014;16(5):225-229. 
5. Alexiades-Armenakas M, Newman J, Willey A, et al. Prospective multicenter clinical trial 
of a minimally invasive temperature-controlled bipolar fractional radiofrequency system 
for rhytid and laxity treatment. Dermatol Surg. Feb 2013;39(2):263-273. 
6. Gold M, Taylor M, Rothaus K, Tanaka Y. Non-insulated smooth motion, micro-needles RF 
fractional treatment for wrinkle reduction and lifting of the lower face: International 
study. Lasers Surg Med. Oct 2016;48(8):727-733. 
7. Dayan, Steven H. MD; Humphrey, Shannon MD; Jones, Derek H. MD; Lizzul, Paul F. MD, 
PhD, MPH, MBA; Gross, Todd M. PhD; Stauffer, Karen PhD, CMPP; Beddingfield, 
Frederick C. III MD, PhD. Overview of ATX-101 (Deoxycholic Acid Injection): A 
Nonsurgical Approach for Reduction of Submental Fat. Dermatologic Surgery: November 
2016 - Volume 42 - Issue - p S263–S270 
8. Jones DH, Carruthers J, Joseph JH, et al. REFINE-1, a multicenter, randomized, double-
blind, placebo-controlled, phase 3 trial with ATX-101, an injectable drug for submental 
fat reduction. Dermatologic Surg. January 2016 - Volume 42 - Issue 1 - p 38-49. 
9. Lemperle G, Holme RE, Cohen ST, et al. A classification of wrinkles. Plastic Reconstr Stug. 
Nov 2001;108(6):1735-50. 
10. Carruthers A, Donofrio L, Hardas B, et al. Development and Validation of a 
Photonumeric Scale for Evaluation of Static Horizontal Forehead Lines. Dermatol Surg. 
Oct 2019;42(S1):S243-S250. 
11. Carruthers J, Donofrio L, Hardas B, et al. Development and Validation of a Photonumeric 
Scale for Evaluation of Facial Fine Lines. Dermatol Surg. 2016;42(S1):S227-S234. 
12. Jones D, Carruthers A, Hardas B, et al. Development and Validation of a Photonumeric 
Scale for Evaluation of Transverse Neck Lines. Dermatol Surg. Oct 2016;42(S1):S235-
S242. 
13. Donofrio L, Carruthers A, Hardas B. Development and Validation of a Photonumeric 
Scale for Evaluation of Facial Skin Texture. Dermatol Surg. Oct 2016;42(S1):S219-S226. 
14. Dayan E, Chia C, Burns AJ, et al. Adjustable Depth Fractional Radiofrequency Combined 
with Bipolar Radiofrequency: A Minimally Invasive Combination Treatment for Skin 
Laxity. Aesthet Surg J. Apr 2019;39(S1):S112-S119.   
 
 
 
 
 
22. Appendix 
I. 
Lemperle Wrinkle Assessment Scale9 

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II. 
Allergan Fine Lines Scale11 
a. 
 
b. 
 
 
 
 
 
 
 
III. 
Allergan Skin Roughness Scale for Evaluation of Facial Skin Texture13 

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a. 
 
b. 
 
 
IV. 
Global Aesthetic Improvement Scale (GAIS) 
 
Rating 
Description 
1 
Very Much Improved: Optimal cosmetic result in this subject. 
2 
Much Improved: Marked improvement in appearance from the initial 
condition, but not completely optimal for this subject. 
3 
Improved: Obvious improvement in appearance from initial condition, but a 
re-treatment is indicated. 
4 
No Change: The appearance is essentially the same as the original condition. 
5 
Worse: The appearance is worse than the original condition. 
 
V. 
Patient Satisfaction Questionnaire 

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