Comparison of 1,550-nm Laser and Fractional Radiofrequency Microneedle for the Treatment of Acne Scars in Ethnic Skin

Study Overview
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Brief Summary
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The primary objective of this randomized, split-face, controlled study is to compare the efficacy and safety of a erbium-doped 1,550-nm non-ablative fractional laser and a bipolar fractional radiofrequency microneedle device for the treatment of atrophic facial acne scars in ethnic skin (Fitzpatrick Skin Phototypes III-VI). The hypothesis of this study is that both erbium-doped 1,550-nm non-ablative fractional laser and the bipolar fractional radiofrequency microneedle device are equally effective for the treatment of atrophic acne scars in ethnic skin (SPT III-VI). However, the bipolar fractional radiofrequency microneedle device has less adverse effects than erbium-doped 1,550-nm non-ablative fractional laser due to the absence of scattering and the absence of chromophore-specific targets - predominantly melanin - traditionally needed with laser treatments; hence the fractional radiofrequency microneedle device will have a higher safety profile in darker skin types .

Detailed Description
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Acne is a highly prevalent disease and post-acne scaring has shown to have detrimental effects on a person's physical, mental, and social well-being. Acne scars can be divided in general categories of hypertrophic or keloid scars, atrophic scars (icepick, rolling, boxcar), and pigmentation alterations (redness, hypo and hyper-pigmentation). This study will focus on treatment of moderate to severe grades of atrophic acne scarring. Our aim is to compare the efficacy and safety of a erbium-doped 1,550-nm non-ablative fractional laser and a bipolar fractional radiofrequency microneedle device for the treatment of atrophic acne scars in ethnic skin (Fitzpatrick Skin Phototypes III-VI) by performing a split-face randomized controlled trial. Both devices in this study are already FDA approved treatment modalities for acne scarring. History of erbium-doped 1,550-nm non-ablative fractional laser (Fraxel® Restore Laser System, Solta Medical, Inc., Hayward, CA): Non-ablative fractional lasers work via the theory of fractional photothermolysis, which creates hundreds to thousands of microscopic thermal zones (MTZs), or columns of thermally injured skin, while sparing the surrounding tissue. The pixilated nature of treatment and the functionally unimpaired stratum corneum allow for rapid tissue healing and allows for safer treatments of our patients. Mechanistically, fractional photothermolysis allows controlled amounts of high energy to be delivered deep within the dermis resulting in collagenolysis and neocollagenesis, which smoothes the textural abnormalities of acne scarring. Multiple published studies have demonstrated that erbium-doped 1,550-nm non-ablative fractional laser (NAFL) can be successfully utilized in the treatment of all forms of atrophic acne scarring - ice-pick, boxcar, and rolling scars - with a very favorable safety profile in all skin types, and thus, has been cleared by Food and Drug Administration (FDA) for that particular indication. According to the manufacture manual (reference attached in the Attachments section), NAFL is indicated for use in skin resurfacing procedures as well as treatment of acne scars, surgical scars, lentigos (age spots), solar lentigos (sun spots), actinic keratosis, and melasma. History of the fractional radiofrequency microneedle device (Fractora; Invasix Ltd./InMode MD Ltd., Israel): Fractional radiofrequency is not a laser. Instead, these devices use an array of electrodes that allows for zones of thermal wounds to be created between areas of unaffected zones, thus stimulating dermal remodeling and allowing for a supply of reservoir cells to promote healing. Variations of fractional radiofrequency exist that employ microneedles to deliver electrical current to a particular depth within the dermis that decreases damage to the epidermis. These fractional radiofrequency microneedle devices provide an alternative to conventional methods of acne-scar treatment (such as NAFL). Great interest has been culminating over the recent years for the use of such devices in acne scars due to the absence of light scattering and the absence of chromophore-specific targets traditionally needed with laser treatments. As melanin is not a target, it is felt to have a higher safety profile in darker skin phototypes. A recent study investigated the safety and efficacy of a specific bipolar fractional radiofrequency microneedle device (Fractora; Invasix Ltd./InMode MD Ltd., Israel) for acne and acne scarring. In this study, 8 patients with acne scars were reported and it was noted that all patients (regardless of their skin phototypes) had improvement in their active acne and acne scars after 4 treatments and a 1 month, on average follow-up period. The treatment was well tolerated without any side-effects. Skin biopsies from this study showed reduction in scar depth and new collagen formation with an increase in elastic fibers and adnexal structures noted. A follow-up report showed that 4 out of 8 patients who were in the original study returned for a long term follow-up from 1 to 2 years, that showed ongoing clinical improvements in these patients. This specific bipolar fractional radiofrequency microneedle (FRM) device has been FDA-approved for acne scars and skin rejuvenation. To this date the efficacy and safety of 1,550-nm fractionated photothermolysis system has not been compared to a fractional radiofrequency microneedle device for atrophic acne scars in ethnic skin in a randomized split-face controlled trial. A major advantage of a split-face self-controlled design would be to minimize any confounding factors. Laser resurfacing has been well studied and is widely used in individuals with fair skin - Fitzpatrick skin phototypes (SPT) I to II. However, there is a paucity of published studies involving individuals with darker skin types (SPT III-VI)-a population that has a higher risk of laser-associated dyspigmentation.

Official Title
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Comparison of Fractional Erbium-Doped 1,550-nm Laser and a Bipolar Fractional Radiofrequency Microneedle Device for the Treatment of Atrophic Acne Scars in Ethnic Skin: A Randomized Split-Face Controlled Pilot Study

Conditions
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Acne Scars

Intervention / Treatment
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* Device: Fraxel Restore
* Device: Fractora


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women with Fitzpatrick skin types III through VI and facial acne scarring of grades III-IV will be enrolled. Both sides of the participants' face should have almost similar amount and severity of acne scarring. Participants will be over 18 years old Exclusion Criteria: Patients have to be overall healthy without a history of keloidal scarring, localized or active infection in the treatment region, immunodeficiency disorders, porphyria or light sensitivity, and connective tissue disorders. Per PI discretion, any serious medical condition that may interfere with the study. In addition, pregnant or nursing women, patients who have been taking isotretinoin for a period of 6 months before treatment, and patients who have received any cosmetic treatment (lasers, dermabrasion, chemical peels, etc) in the previous 6 months will be excluded. Also, patients with renal disease, and any allergies to Lidocaine, Tetracaine, or Valtrex will be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Randomized split-face clinical trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fraxel Restore on one side of the face<br>Fraxel Restore on one side of the face Fraxel Restore: acne scar correction Randomized treatment with Fraxel Restore on one side of the face, and Fractora on the opposite side of the face - the study is a randomized,single-center, split-face study in subjects seeking acne scar correction. Subjects were treated with Fraxel on one side of the face and Fractora on the other side of the face. The side of the face for each device was randomly assigned. | Device: Fraxel Restore<br>* Non-ablative Laser. In the study, one side of the face will be treated with Fraxel Restore monthly for three months.<br>|
| Active Comparator: Fractora on the other side of the face<br>Fractora on the other side of the face Fractora: acne scar correction Randomized treatment with Fraxel Restore on one side of the face, and Fractora on the opposite side of the face - the study is a randomized,single-center, split-face study in subjects seeking acne scar correction. Subjects were treated with Fraxel on one side of the face and Fractora on the other side of the face. The side of the face for each device was randomly assigned. | Device: Fractora<br>* Fractional Radiofrequency Microneedling Device. In the study, one side of the face will be treated with Fractora monthly for three months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in Acne Scarring - From Baseline to Three Months After Last Treatment | Improvement in acne scarring will be measured by two blinded evaluators both by in-person assessments and by photographic review (digital photography will be used under standardized conditions). A quartile grading scale (1 = 1% to 25%, 2 =26% to 50%, 3 =51% to 75%, 4 = >76% improvement) will be used to measure acne scar improvement. Higher score means better outcome. | three months after last treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparing Side Effects of the Different Lasers | measure side effects by patient reported adverse events and blinded physician assessment of adverse effects. Parameters, include erythema, edema, blistering, crusting, scarring, hypopigmentation, and hyperpigmentation, will be graded on a 4-point scale (0 = absent, 1= mild, 2 = moderate, and 3 = severe). Higher score means worse outcome. | treatment visit 1, treatment visit 2, treatment visit 3, three months after last treatment | 
| Comparing Intensity of Pain With the Different Lasers | Patients will also be evaluated the intensity of pain using a visual analogue scale (0 = absence of pain, 10 = most-severe pain). Higher score means worse outcome | treatment visit 1, treatment visit 2, treatment visit 3 |