Radio Frequency Microneedling for Suprapatellar Skin

Study Overview
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Brief Summary
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The human skin aging process is characterized by thinning dermis, atrophy of the extracellular matrix, and reduced collagen synthesis. 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. This is histologically seen as disorganized tangles of elastin. Additionally, as humans age, skin tends to appear more dry due to its poor hydration and turgor capacity. The use of minimally invasive aesthetic treatments in reducing signs of aging has been gaining in popularity over surgical treatments in recent years. Several energy types including, laser, radiofrequency, infrared, and ultrasound, have been developed for facial rejuvenation. These treatments induce controlled thermal damage into the dermis and cause collagen contraction and neocollagenesis resulting in skin tightening over several months. For improving appearance of other anatomical areas, micro-focused ultrasound has been the preferred method, but has shown limited success in tightening the suprapatellar skin. As with facial skin aging, the suprapatellar skin loses elasticity with age and begins to sag. Noninvasive treatments used for the face may also be used in other anatomical areas to produce the same effects of tightening. Minimally invasive bipolar radiofrequency produces a controlled thermal injury in a fractional manner without damaging the dermal-epidermal junction, epidermis or subcutis. Radiofrequency, unlike lasers, are chromophore-independent providing better penetration than lasers, and spare sweat glands, sebaceous glands, and hair follicles.

Detailed Description
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The Profound System is a bipolar fractional radiofrequency device which uses microneedles and thermal heat to stimulate neocollagenesis. Based on the its effect on facial skin, it can be hypothesized that bipolar fractional radiofrequency will stimulate similar effect on suprapatellar skin, lifting and reducing laxity of the skin in that region. This study intends to evaluate the effectiveness of the Profound System on suprapatellar skin, which has been FDA approved for treatment of facial wrinkles and improvement in the appearance of cellulite. This device is a well studied and frequently used on facial skin, however, there are no studies showing its effectiveness elsewhere on the body. There are alternative treatments that have been shown to decrease laxity of the suprapatellar skin, however, the studies include a small and limited population, and have not produced the desired effects in practice. The Profound device may be able to produce clinically significant improvement in laxity of the suprapatellar skin.

Official Title
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Pilot Study: Clinical Assessment of Bipolar Radiofrequency Microneedling for Improved Laxity and Wrinkles of the Suprapatellar Skin

Conditions
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Skin Laxity

Intervention / Treatment
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* Device: Profound system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female adults between ages 18-75 years of age. Subjects who can read, understand, and sign the Informed Consent Form. Subjects willing and able to comply with all study requirements Fitzpatrick skin type I-III Exclusion Criteria: Subjects with active localized or systemic infections. Immunocompromised subjects. Subjects with coagulation disorder. History of skin photosensitivity disorders, or use of photosensitizing drugs (e.g., tetracycline or sulfa drugs). Pregnant and/or lactating (All female volunteers will be advised about using birth control during the period of study). In the opinion of the trained clinician, subject is unwilling or unable to adhere to all study requirements, including application and follow-up visits. Subjects with a history of radiation therapy to the treatment area. Subject has a history of allergy to lidocaine or ester-based local anesthetics. Subjects with any skin pathology or condition that could interfere with evaluation or with the use of typical ancillary medical treatments or care used before, during or after treatments. Subjects have undergone dermatological procedures (e.g., laser or light treatments) for the treatment of wrinkles, skin resurfacing, or skin rejuvenation in the treatment area within 1 year of study participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>All patients will undergo treatment with Profound system device. Using the radiofrequency and temperature setting within the FDA approved limits (460 +/- 5kHz and 65-75°C +/- 1°C), patients will be treated one time over the entire suprapatellar region bilaterally and followed for a 6 month period. The acute effect of the radiofrequency application will be determined by subjective and objective analysis using standard, close-up, 3D, cross-polarized, high resolution ultrasound, optical coherence tomography, transepidermal water loss measurements, and/or BTC 2000 measurements. Biopsies will be taken using 0.33mm WellTech Rapid Core 0.33mm Biopsy Punch. Biopsies will allow investigators to correlate changes seen in skin measurements with histology and gene expression. | Device: Profound system<br>* Profound system is a bipolar fractional radiofrequency device which uses microneedles and thermal heat to stimulate neocollagenesis. Based on the its effect on facial skin, it can be hypothesized that bipolar fractional radiofrequency will stimulate similar effect on suprapatellar skin, lifting and reducing laxity of the skin in that region. Bilateral suprapatellar regions will be identified and marked for treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Photographic Knee Laxity and Texture Evaluation | Photographs will be used to evaluate efficacy of treatment. The photographs from final visit will be compared to their baseline photographs and visually evaluated by the study team. The study team will assess the laxity from baseline to 6 months. | baseline and 6 months | 
| Epidermal Thickness | Skin Elasticity will be measured via BTC2000 prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. The change from baseline was calculated at each time frame. | baseline, 7 Days, 3 Weeks, 3 Months and 6 Months | 
| Dermal Thickness | Dermal thickness will be masured via high resolution ultrasound prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. The change from baseline was calculated at each time frame. | Baseline, 7 Days, 3 Weeks, 3 Months and 6 Months | 
| Change in Blood Flow at 0.25mm | Blood Flow will be measured via optical coherence tomography prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. | Baseline, Day 7, Week 3 Month 3 and Month 6 | 
| Transepidermal Water Loss | Transepidermal Water Loss will be masured via Aquaflux prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. The change from baseline was calculated at each time frame. | Baseline, Day 7, Week 3, Month 3 and Month 6 | 
| Skin Elasticity | Skin Elasticity will be measured via BTC2000 prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. The change from baseline was calculated at each time frame. | Baseline, Day 7, Week 3, Months 3 and Months 6 | 
| Change in Skin Laxity | BTC2000 will be used to measure skin laxity prior to treatment and post treatment. The BTC2000 is a non-invasive device that measures skin laxity by creating a negative pressure against the skin and calculates laxity when the pressure is released. | baseline, 7 days, 3 weeks, 3 months and 6 months | 
| Histological Analysis- Collagen 1 | Relative changes in protein abundance in biopsies taken at post treatment compare to control or entreated group will be quantified using an image processing software based on fluorescence signal intensity. The change from baseline was calculated at each time frame. | Baseline. Day 7 and 3 Months | 
| Gene Expression- Collagen 1 | Biopsies of the treated are will be taken prior to treatment and post treatment for gene expression analysis. This analysis will identify gene expression related to collagen formation and increased cell turnover. Fold change was calculated at each time point past baseline. Fold change = sample/average of the baseline. | Day 7, Month 3 | 
| Epidermal Density | Epidermal thickness will be masured via high resolution ultrasound prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. The change from baseline was calculated at each time frame. | Baseline, Day 7, Week 3, Month 3 and Month 6 | 
| Histological Analysis- Collagen 3 | Relative changes in protein abundance in biopsies taken at post treatment compare to control or entreated group will be quantified using an image processing software based on fluorescence signal intensity. The change from baseline was calculated at each time frame. Sample/Average of the baseline. | Baseline, Day 7, Month 3 | 
| Histological Analysis- Elastin | Relative changes in protein abundance in biopsies taken at post treatment compare to control or entreated group will be quantified using an image processing software based on fluorescence signal intensity. The change from baseline was calculated at each time frame. Samples/Average of the baseline | Baseline, Day 7, Month 3 | 
| Gene Expression- Collagen 3 | Biopsies of the treated are will be taken prior to treatment and post treatment for gene expression analysis. This analysis will identify gene expression related to collagen formation and increased cell turnover. Fold change = sample/average of the baseline. | Day 7, Month 3 | 
| Gene Expression- Elastin | Biopsies of the treated are will be taken prior to treatment and post treatment for gene expression analysis. This analysis will identify gene expression related to collagen formation and increased cell turnover. Fold change = sample/average of the baseline. | Day 7, Month 3 | 
| Gene Expression- Interluekin 6 | Biopsies of the treated are will be taken prior to treatment and post treatment for gene expression analysis. This analysis will identify gene expression related to collagen formation and increased cell turnover. Fold change = sample/average of the baseline. | Day 7, Month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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knee area, suprapatellar skin, aging, laxity