Superficial MFU-V and Diluted Calcium Hydroxyapatite for the Improvement of Lower Face Skin Quality and Wrinkles

Study Overview
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Brief Summary
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Aging, genetics and environmental factors contribute to multiple changes on the surface of the skin. These present with pigmentation, volume loss, loss of elasticity and loss of collagen. Altogether, areas of the face becomes crepey, with resulting rhytids and an obvious appearance of thin and fragile skin. These are typically dermal manifestations of elastin and collagen loss resulting in a collective term of loss of skin quality. Current treatments to improve these changes involve the use of skincare, chemical peels, as well as more invasive repeated treatments such as microneedling and laser resurfacing. These commonly require repeated treatments and several days of downtime. More recently, treatment with a hybrid preparation of high and low-molecular weight complexes that are thermally cross-linked (Profhilo) has been suggested to stimulate collagen and elastin formation, thereby resulting in improvement in skin quality.

Detailed Description
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Aging, genetics and environmental factors contribute to multiple changes on the surface of the skin. These present with pigmentation, volume loss, loss of elasticity and loss of collagen. Altogether, areas of the face becomes crepey, with resulting rhytids and an obvious appearance of thin and fragile skin. These are typically dermal manifestations of elastin and collagen loss resulting in a collective term of loss of skin quality. Current treatments to improve these changes involve the use of skincare, chemical peels, as well as more invasive repeated treatments such as microneedling and laser resurfacing. These commonly require repeated treatments and several days of downtime. More recently, treatment with a hybrid preparation of high and low-molecular weight complexes that are thermally cross-linked (Profhilo) has been suggested to stimulate collagen and elastin formation, thereby resulting in improvement in skin quality However, the evidence for this remains limited. Microfocused Ultrasound with Visualization (MFU-V) and Calcium hydroxylapatite (CaHA) have each been unequivocally proven to stimulate neocollagenesis and elastogenesis, leading to improvement in skin laxity. A recent study of a single-treatment single-depth of superficial MFU-V was found to result in aesthetic improvement of the accordion lines. In addition, there is recent evidence that CaHA in a hyperdiluted form can stimulate collagen and elastin formation. Indeed, this group of investigators has recently published the effectiveness of a single treatment of a combination MFU-V and diluted CaHA for improving brachial skin laxity. Arguably, there is a need to publish additional studies on these interventions for improving firmness and skin quality. In addition, there may be a theoretical cumulative benefit in using both treatments for improving skin quality, although the effectiveness of this combination has not been demonstrated. With this background, the main rationale of performing this study is to demonstrate the safety and efficacy of a multimodality approach with a single treatment of superficial MFU-V and diluted CaHA for improvement of skin quality in Asian and Caucasian patients. The investigators selected Lower Face as the target area for the following reasons: 1) The Lower Face manifests the greatest with thinning, fine wrinkling and general fragility of the skin, 2) Volumization is not always aesthetically pleasing in this area but firmness of the skin is, 3) This area is an established treatment area for MFU-V, CaHA but not with other treatment options such as Profhilo.

Official Title
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Superficial MFU-V and Diluted Calcium Hydroxyapatite for the Improvement of Lower Face Skin Quality and Wrinkles

Conditions
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Aging

Intervention / Treatment
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* Device: Ulthera System [Ulthera, Inc.]
* Device: Merz Radiesse Injectable Implant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients with lower face wrinkles Otherwise generally healthy. Physically and mentally capable to provide informed consent to the study. Agreement to attend all follow-up visits as scheduled Exclusion Criteria: Pregnancy or lactation; History of allergic reaction to calcium hydroxylapatite injection; Active local infections or skin diseases that might alter wound healing Acne or keloidal scarring Use of immunosuppressive drugs Any other diseases which can affect the wound-healing process Any procedures affecting facial wrinkles or skin quality in the lower face for the duration of the study Microdermabrasion and Peels Acne treatments Filler and Botulinum Toxin treatments Radiofrequency, Laser, IPL, Ultrasound Patients that had cosmetic treatments within 3 months of the baseline visit in the treatment area Subjects with dermatologic conditions in the treatment area including: Acne Rosacea Eczema Psoriasis Actinic keratosis, Severe sun damage Scars or a history of keloids

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: This is a single centre prospective pilot study to evaluate the efficacy of combining MFU-V and diluted CaHA for improving skin quality on the lower face. Treatment protocols are as follows: MFU-V delivered to the lower face areas as drawn using a single transducer with a focal depth of 1.5mm (following a previously published paper (Lowe, 2021) but with extension of the lower treatment area to the two-ruler width (Ulthera marking ruler) as treatment zones. Application will be delivered through a cross-hatching technique. Immediately following MFU-V or up to a week after, diluted CaHA will be administered following the Global Consensus Guidelines published in 2018 by de Almeida et al as follows 1) 1 syringe or 1.5ml of CaHA diluted 1:1 with saline for a total of 3ml of solution or 1.5 diluted CaHA per side will be injected in the subdermal plane with a cannula using a retrograde fanning technique.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ultherapy and Radiesse<br>Delivered to the lower face areas as drawn using a single transducer with a focal depth of 1.5mm (following a previously published paper (Lowe, 2021) but with extension of the lower treatment area to the two-ruler width (Ulthera marking ruler) as treatment zones. Application will be delivered through a cross-hatching technique. Immediately following MFU-V or up to a week after, diluted CaHA will be administered following the Global Consensus Guidelines published in 2018 by de Almeida et al as follows 1) 1 syringe or 1.5ml of CaHA diluted 1:1 with saline for a total of 3ml of solution or 1.5 diluted CaHA per side will be injected in the subdermal plane with a cannula using a retrograde fanning technique. | Device: Ulthera System [Ulthera, Inc.]<br>* The Ulthera System is indicated for: - Use for noninvasive dermatological sculpting and lifting of the dermis: Upper Face, Lower Face, Neck, Décolletage. - Non-invasive treatment of Axillary Hyperhidrosis<br>Device: Merz Radiesse Injectable Implant<br>* Radiesse injectable implant is an opaque, sterile, non-pyrogenic, semi-solid, cohesive implant. The principal component is synthetic CaHA suspended in a gel carrier that consists primarily of water (sterile water for injection, United States pharmacopeia (USP)), glycerin (USP), and sodium carboxymethylcellulose (USP). Radiesse injectable implant (1.5mL syringe unit) has a CaHA particle size range of 25-45 microns and should be injected sub-dermally with a 27 gauge needle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Skin Quality | Pre and post treatment comparison of change in skin quality. These will be measured using Quantificare LifeViz Micro, an established tool to objectively measure and validate treatment results of skin quality which will allow to accurately quantify changes with specific measurement tools. | 1 Month, 3 Months and 6 Months post intervention | 
| Change in Wrinkle Reduction | Pre and post treatment comparison of change in dimensions of fine lines (volume/depth/length). These will be measured using Quantificare LifeViz Micro, an established tool to objectively measure and validate treatment results of lines, which will allow to accurately quantify changes with specific measurement tools. | 1 Month, 3 Months and 6 Months post intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Aesthetic Improvement Score | Pre and post treatment comparison of Visual Aesthetic Improvement Score of standardized patient photographs by study investigators. Both VISIA Imaging photographs and standard photographs will be used. | 1 Month, 3 Months and 6 Months post intervention |