Combined LASERs and PRP for Postacne Scars

Combined Fractional LASERs Resurfacing With Platelets Rich Plasma (PRP) for Treating Post Acne Atrophic Scarring

This study evaluates a new combined technique using two different laser wavelengths and Platelets Rich Plasma (PRP) to treat post-atrophic acne scars. Within the available knowledge of laser-tissue interactions and effects of PRP on wound healing, we will explore the clinical effects of our new combination procedure on a histopathological and immunohistochemical basis for guiding future post acne scars clinical research.

Study Overview

• Status: Completed
• Conditions: Atrophic Acne Scar
• Intervention / Treatment: Device: Lasers; Combination product: Lasers plus Normal Saline Solution; Other: Platelets Rich Plasma

Detailed Description

The carbon dioxide and erbium lasers have been the gold and silver standards for acne scars treatment. As with selective photothermolysis, a major advance in the field is the incorporation of grids of MicroThermal Zones (MTZ) that spares islands of skin with an attractive treatment efficacy to downtime healing (5-7 days) ratio. Application of these fractionated resurfacing to carbon dioxide and erbium lasers allows deeper penetration into the skin.

Fractional photothermolysis was first described by as a new method for delivery of laser energy with the potential of laser safety and efficacy. Through the delivery of microscopic, non-contagious zones of thermal damage using a 1550 nm, mid-infra-red laser source, it was observed that surrounding islands of dermal and epidermal cells facilitated post-treatment collagen remodeling and rapid healing. Despite the success of minimally ablative and fractional technologies, there remained a need for more aggressive tissue ablation for the purposes of tissue rejuvenation of severely photodamaged skin and deeper rhytides. This might be due to the variability of architecture, depth, and width; thus, each type of scar has an optimal method by which it can be improved.

The idea of combining both carbon dioxide and erbium lasers appeared even before the era of fractional lasers. McDaniel et al, combined both non-fractional lasers for resurfacing of perioral rhytides comparing it to using carbon dioxide lasers alone and concluded that carbon dioxide laser resurfacing followed by 3 passes of erbium laser reduces the duration of crusting, swelling and itching when compared to carbon dioxide laser resurfacing alone with no significant difference in the outcome.

Later in 2010, the combination of fractional lasers carbon dioxide and erbium-doped laser was tried out for treating mild acne scars by a group of researchers. They reported a longer post laser erythema and hyperpigmentation, without precise pathogenesis. However, they suggested that these unexpected outcomes may have resulted from bulk heat damage to the surrounding tissues by heat stacking and recommended further studies to determine the optimal treatment parameters and reduce unexpected adverse reactions.

Platelet-rich plasma (PRP) is a high concentration of platelets in a small volume of plasma. PRP contains various growth factors and cytokines released by platelets, and those substances play a critical role in all aspects of the wound healing process. Among the stored mitogenic factors essential for wound repair are platelet-derived growth factor (PDGF) with the -AB and -C isoforms predominating, transforming growth factor β (TGF-β), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived epidermal growth factor (PDEGF) and insulin-like growth factor-1 (IGF-1). These are variously involved in stimulating chemotaxis, cell proliferation, and maturation. PDGF is a powerful chemoattractant and stimulator of cell proliferation. All of them are potent angiogenic factors and endothelial cell mitogens. The wound healing effect of PRP is relatively well known, and PRP has been used in bone surgery, tendon and ligament repair, and chronic leg ulcer treatment.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Calenzano
    • Firenze, Calenzano, Italy, 50041
      • DEKA M.E.L.A. S.r.l.
• Kuwait
  • Al Qādisīyah, Kuwait, 35858
    • Cosmetic Surgery Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with atrophic post-acne scars.
2. Patients without surgical &/or LASER resurfacing treatment for acne scars within the last 6 months.

Exclusion Criteria:

1. Pregnancy
2. Present or past history of hypertrophic scars or keloids
3. Present or past history of photosensitivity dermatoses including Connective Tissue Diseases.
4. Present history of herpes infection
5. Present history of Anemia (HGB < 10 g/dl), Thrombocytopenia &/or Platelets dysfunction.
6. Patients receiving isotretinoin within the last 3 months, NSAIDs within 72 hours of the procedure, anticoagulants &/or systemic use of corticosteroids within 2 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Control; 32 biopsy specimens from acne scars will be excised without any treatment.
SHAM_COMPARATOR: Lasers plus Normal Saline Solution; 32 biopsy specimens will be excised immediately after being treated with lasers and subsequent injection of normal saline solution.	Device: Lasers; Fractional carbon dioxide laser will be applied only over spots of deep post-acne scars, while Erbium: Glass will be applied all over face except to the two predetermined spots, i.e. control and another spot where NSS will be injected.; Other Names: Fractional CO2 and Erbium Glass Lasers; Combination product: Lasers plus Normal Saline Solution; Normal Saline Solution will be injected only in one spot after combined lasers resufacing to act as sham comparator compared to the other spot of Lasers plus PRP injection; Other Names: NSS
ACTIVE_COMPARATOR: Lasers plus Platelets Rich Plasma (PRP); 32 biopsy specimens will be excised immediately after being treated with lasers and subsequent injection of platelets Rich Plasma (PRP).	Device: Lasers; Fractional carbon dioxide laser will be applied only over spots of deep post-acne scars, while Erbium: Glass will be applied all over face except to the two predetermined spots, i.e. control and another spot where NSS will be injected.; Other Names: Fractional CO2 and Erbium Glass Lasers; Other: Platelets Rich Plasma; Platelet Rich Plasma (PRP) will be prepared from autologous blood collection in a syringe prefilled with anticoagulant solution followed by centrifugation then adding calcium gluconate 10% for induction of platelet activation. Activated PRP will be injected for all carbon dioxide laser spots in each patient immediately after each laser session except for two predetermined spots, i.e. control and sham comparator, which will be injected by normal saline solution (NSS).; Other Names: PRP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Patients' response denoting early Clinical improvement	calculating the change in 17 questions' responses of a new Patient Oriented Tool questionnaire for assessing Atrophic Acne Scarring through two parts; a) assessment of Acne Scar Appearance and b) Acne Scar Quality of Life questionnaire. Patients will record their responses before the 1st session and on the date of 2nd session.	4 weeks after the 1st session
Final Clinical improvement assessed using (0-10) scoring scale by blind assessors	The change in scores comparing 2 sets of digital photographs for each patient evaluated by 3 blind assessors, before and after 12 weeks of the 4th session. This blind assessment score will be compared to patients' score in their previous questionnaire.	12 weeks after the 4th session

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Higher new collagen formation in scars treated using lasers plus PRP technique	Picrosirus Red stained specimens under circularly polarized microscopy will be segmented into two color threshold bands (Green/Yellow G/Y and Red/Orange R/O) in the color HSB space. This will be numerically evaluated using ImageJ computer program	Immediately after the 1st session
Immunohistochemical evaluation of Collagen I, Collagen III, and MMP-2	Using a 4 grade scale (0, +, ++, +++), the 288 slides (i.e. 3 slides prepared from 96 specimens obtained from 32 patients) will be arranged for comparison among control, sham comparator and, active comparator. Also, results will be correlated to previous numerical ImageJ computerized assessment and patients' clinical improvement.	Immediately after the 1st session

Collaborators and Investigators

• Sponsor: DEKA S.r.l.
• Collaborators: Universitat Autonoma de Barcelona
• Investigators: Study Director: Lluis Puig, MD, PhD, Universitat Autonoma de Barcelona (UAB); Principal Investigator: Alberto Calligaro, MD, PhD, University of Pavia

Publications and helpful links

General Publications

• Layton A, Dreno B, Finlay AY, Thiboutot D, Kang S, Lozada VT, Bourdes V, Bettoli V, Petit L, Tan J. Erratum to: New Patient-Oriented Tools for Assessing Atrophic Acne Scarring. Dermatol Ther (Heidelb). 2016 Jun;6(2):235-6. doi: 10.1007/s13555-016-0107-8. No abstract available.
• Manstein D, Herron GS, Sink RK, Tanner H, Anderson RR. Fractional photothermolysis: a new concept for cutaneous remodeling using microscopic patterns of thermal injury. Lasers Surg Med. 2004;34(5):426-38. doi: 10.1002/lsm.20048.
• Cho SB, Lee SJ, Kang JM, Kim YK, Oh SH. Combined fractional laser treatment with 1550-nm erbium glass and 10 600-nm carbon dioxide lasers. J Dermatolog Treat. 2010 Jul;21(4):221-8. doi: 10.1080/09546630903089650. No abstract available.
• Lee JW, Kim BJ, Kim MN, Mun SK. The efficacy of autologous platelet rich plasma combined with ablative carbon dioxide fractional resurfacing for acne scars: a simultaneous split-face trial. Dermatol Surg. 2011 Jul;37(7):931-8. doi: 10.1111/j.1524-4725.2011.01999.x. Epub 2011 Jun 2.
• Prignano F, Campolmi P, Bonan P, Ricceri F, Cannarozzo G, Troiano M, Lotti T. Fractional CO2 laser: a novel therapeutic device upon photobiomodulation of tissue remodeling and cytokine pathway of tissue repair. Dermatol Ther. 2009 Nov;22 Suppl 1:S8-15. doi: 10.1111/j.1529-8019.2009.01265.x.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2018
• Primary Completion (ACTUAL): June 30, 2019
• Study Completion (ACTUAL): October 30, 2019

Study Registration Dates

• First Submitted: January 14, 2019
• First Submitted That Met QC Criteria: January 15, 2019
• First Posted (ACTUAL): January 18, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 29, 2019
• Last Update Submitted That Met QC Criteria: November 26, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: PRP; Acne scars; fractional lasers
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Atrophy
• Other Study ID Numbers: AY001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: No