Microneedle Versus Fractional CO₂ Laser for Skin Aging Treatment With Stem Cell Secretome in Indonesian Adult Women

Study Overview
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Brief Summary
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Evidences regarding the effectiveness of adipose-derived mesenchymal stem cells (ADMSCs) secretome to alleviate skin aging have been extensively available, yet no studies hitherto directly investigated the best administration technique for such purpose. The objective of this study is to compare microneedling and fractional CO₂ laser methods in administrating ADMSCs secretome for facial skin rejuvenation of Indonesian adult women.

Detailed Description
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A single-blind, randomized clinical trial will be conducted upon thirty females (aged 35-59 years old) presented with signs of generalized facial cutaneous senescence. Their initial skin status will be evaluated utilizing dermoscopy photoaging scale (DPAS) and Janus-3® skin analyzer, along with skin capacitance using the Corneometer® and transepidermal water loss using the Tewameter®, followed by daily priming with 0.05% retinoic acid for two consecutive weeks. At second and fourth week, the participants are subjected to microneedle and fractional CO₂ laser according to the respective protocol in split-face fashion, which the randomization will be determined by a computer programme. Succeeding the treatment, four-fold concentrated ADMSCs secretome will be administered topically to the both sides of face. The final skin condition will ultimately be recorded at the sixth week, along with their satisfaction and convenience degree, the adverse events experienced during the trial, and subjective preference to the treatment. Appropriate statistical analyses will subsequently be performed at the significance level of 0.05.

Official Title
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Microneedling Versus Fractional CO₂ Laser Resurfacing for Skin Rejuvenation With Adipose-derived Mesenchymal Stem Cells Secretome: a Single-blind, Randomized Clinical Trial

Conditions
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Skin Aging, Transepidermal Water Loss

Intervention / Treatment
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* Device: Fractional CO₂ Laser
* Device: Microneedle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female, aged 35-59 years Generalized wrinkles on the face Consent for the 2-month clinical trial (4 times of follow-up with 2 weeks interval) Exclusion Criteria: Prior history of hypertrophic scars or keloid formation Prior history of allergy to topical anesthetic and/or retinoic acid cream Prior history of autoimmune disorders (e.g. systemic lupus erythematosus, rheumatoid arthritis, etc.) Prior history of malignancies Prior utilization of skincare products for the past 6 months Currently under long-term immunosupressants medication (e.g. corticosteroids, biologic agents, cytostatics, etc.) Drop-out Criteria: Pass away during the clinical trial Refrain from the clinical trial before the trial completion Absent for more than two days from the scheduled appointment Suffer from coronavirus disease 2019 (COVID-19) at any time during the trial Experience major adverse event(s) caused by topical products or treatments given in the clinical trial (e.g. allergic drug eruption or contact dermatitis). The participants will receive appropriate management if such event occurs.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 59 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Each participant will receive fractional CO₂ laser treatment on one side of the face and microneedle treatment on the other half. The allocation of which side receive a particular treatment will be determined by a computer programme.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Secretome + Fractional CO₂ Laser<br>This clinical study uses a 4-fold concentrate of ADMSCs secretome developed by PT. Kimia Farma (Persero), Tbk. The secretome is extracted from stem cell line filtered through syringe with pore size of 0.22 µm to eliminate the debris, then concentrated with CorningⓇ Spin-XⓇ UF 500 µL centrifugator. Stabilization analysis is performed before utilization. As for fractional CO₂ laser, AMIⓇ device is used with this following settings: 15 mJ energy, 900 µs pulse duration, density level 15, and depth level 2. | Device: Fractional CO₂ Laser<br>* Prior to the treatment, each participant will be evaluated for their initial skin status, followed by daily priming with 0.05% retinoic acid cream, applied topically at night for two weeks. At second week, the participants will undergo facial skin anesthesia utilizing 2.5% lidocaine+2.5% prilocaine cream for 30 minutes. Half of the face will be irradiated with AMIⓇ fractional CO₂ laser according to the instrument manual for 20 minutes, succeeded by the topical administration of 1.5 mL 4-fold concentrated ADMSCs secretome. The participants are all instructed not to: (1) wash their face for the next 4 hours; (2) apply sunscreen for the next 1 day; and (3) apply retinoic acid cream for the next 3 days. After the restriction, they should use the mentioned products on daily basis until the next appointment when the protocol is repeated (fourth week). At sixth week, the final skin condition is reevaluated with the same tools, along with the additional variables.<br>|
| Experimental: Secretome + Microneedle<br>This clinical study uses a 4-fold concentrate of ADMSCs secretome developed by PT. Kimia Farma (Persero), Tbk. The secretome is extracted from stem cell line filtered through syringe with pore size of 0.22 µm to eliminate the debris, then concentrated with CorningⓇ Spin-XⓇ UF 500 µL centrifugator. Stabilization analysis is performed before utilization. As for microneedle, DrPenⓇ dermapen is used in this following direction and order: vertical, horizontal, and diagonal, with the depth of 150 µm. | Device: Microneedle<br>* Prior to the treatment, each participant will be evaluated for their initial skin status, followed by daily priming with 0.05% retinoic acid cream, applied topically at night for two weeks. At second week, the participants will undergo facial skin anesthesia utilizing 2.5% lidocaine+2.5% prilocaine cream for 30 minutes. The other half of the face will be treated with DrPenⓇ dermapen according to the instrument manual for 20 minutes, succeeded by the topical administration of 1.5 mL 4-fold concentrated ADMSCs secretome. The participants are all instructed not to: (1) wash their face for the next 4 hours; (2) apply sunscreen for the next 1 day; and (3) apply retinoic acid cream for the next 3 days. After the restriction, they should use the mentioned products on daily basis until the next appointment when the protocol is repeated (fourth week). At sixth week, the final skin condition is reevaluated with the same tools, along with the additional variables.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skin aging changes evaluated by dermoscopy photoaging scale (DPAS) | A thorough evaluation using dermoscope upon 11 parameters of skin aging (yellowish papules, solar elastosis, skin atrophy, lentigo, hypopigmented and hyperpigmented macules, telangiectasia, actinic keratosis, senile comedones, superficial wrinkles, deep wrinkles, and criss-cross wrinkles) observed on 4 locations (forehead, periorbita, zygoma, and mandible). Each finding on each location has a value of 1, so the maximum possible total score is 44. *This is a numeric variable. | Week 0 (baseline), week 2 before intervention, week 4 before intervention, week 6 (end of trial) | 
| Skin aging changes evaluated by Janus-3Ⓡ skin analyzer | A comprehensive evaluation using Janus-3Ⓡ skin analyzer upon 4 parameters of skin aging (wrinkle, pore size, pigmentation, and sebum) observed on the same location for each assessment. Each finding is expressed as percentage (%). *This is a numeric variable. | Week 0 (baseline), week 2 before intervention, week 4 before intervention, week 6 (end of trial) | 
| Skin capacitance evaluated by the CorneometerⓇ | Total water content in the stratum corneum of the skin, reported in microsiemens. *This is a numeric variable. | Week 0 (baseline), week 2 before intervention, week 4 before intervention, week 6 (end of trial) | 
| Transepidermal water loss evaluated by the TewameterⓇ | Water evaporation rate in a given area of skin, reported in gram/m²/hour. *This is a numeric variable. | Week 0 (baseline), week 2 before intervention, week 4 before intervention, week 6 (end of trial) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Likert scale for the satisfaction degree | An interval of 0 (extremely unsatisfied) to 10 (extremely satisfied) for determination of the participants' satisfaction upon both treatments (microneedle and fractional CO₂ laser). *This is a numeric variable. | Week 6 (end of trial) | 
| Visual analog scale (VAS) of pain for the convenience degree | An interval of 0 (no pain whatsoever) to 10 (the most extreme pain possible) for determination of the participants' convenience during the trial with both treatments (microneedle and fractional CO₂ laser). *This is a numeric variable. | Week 6 (end of trial) | 
| Number of adverse events experienced during the clinical trial | Side effects experienced by the participants following the application of topical products (facial wash, sunscreen, anesthetic cream, and retinoic acid cream) and procedures (microneedle and fractional CO₂ laser), such as erythema, warmth, itch, burning sensation, edema, peeled skin, and/or no adverse events, reported in frequency of each event. Each participant will be contacted one day after each treatment for side effect evaluation. They can also report any events experienced to the investigator at any time during the trial. *This is a categorical variable. | Week 2 thirty minutes after intervention, week 4 thirty minutes after intervention, week 6 (end of trial) | 
| Subjective preference to treatment | Preference of each subject towards a particular treatment (microneedling or fractional CO2 laser) based on their experience during the trial *This is a categorical variable | Week 6 (end of trial) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adipose-derived mesenchymal stem cells, Fractional CO₂ laser, Microneedling, Secretome, Skin rejuvenation