Efficacy and Tolerance Evaluation of a Bio-revitalizing Product Containing Hyaluronic Acid With High and Low Molecular Weight

Study Overview
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Brief Summary
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Primary end point of the study was to evaluate clinically and by non-invasive instrumental evaluations tolerance and efficacy of a bio-revitalizing product containing hyaluronic acid with high (H-HA) and low (L-HA) molecular weight; the micro-injection of the study product was performed by a specialized dermatologist, bilaterally on the face (zygomatic protuberance, nostril's angle, inferior margin of tragus, lip marionette lines, mandibular angle) of healthy female volunteers aged 30-60 years. It was also aim of this study to evaluate efficacy by the volunteers and tolerance both by investigator and volunteers.

Conditions
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Malar and Sub-malar Volume Deficiency

Intervention / Treatment
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* Device: Profhilo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: female sex age 30-60 years agreeing to present at each study visit without make-up accepting to not change their habits regarding food, physical activity, make-up use, face cosmetic and cleansing products accepting not to expose their face to strong UV irradiation (UV session, or sun bathes), during the entire duration of the study, without appropriate sun protection accepting to sign the Informed consent form. Exclusion Criteria: pregnancy lactation subjects not in menopause who do not use adequate contraceptive precautions in order to avoid pregnancies during the study subjects not in menopause who do not accept to perform the pregnancy test during the basal visit, 4 and 8 weeks after the first biomineralising treatment execution performing skin treatments for aesthetic correction (biomaterials implants, face lifting, botox injections, laser, chemical peeling) in the 12 months prior to the study start performing permanent filler in the past change in the normal habits regarding food, physical activity, face cosmetic, cleansing and make-up use during the month preceding the test sensitivity to the test product or its ingredients (an accurate anamnestic assessment will performed by the investigator) subjects whose insufficient adhesion to the study protocol is foreseeable participation in a similar study actually or during the previous 3 months. presence of cutaneous disease on the tested area, as lesions, scars, malformations recurrent facial/labial herpes clinical and significant skin condition on the test area (e.g. active eczema, dermatitis, psoriasis etc.). diabetes endocrine disease hepatic disorder renal disorder cardiac disorder pulmonary disease cancer neurological or psychological disease inflammatory/immunosuppressive disease drug allergy. anti-inflammatory drugs, anti-histaminic, topic and systemic corticosteroids, narcotic, antidepressant, immunosuppressive drugs (with the except of contraceptive or hormonal treatment starting more than 1 year ago) assumption of drugs able to influence the test results in the investigator opinion.

Ages Eligible for Study
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Minimum Age: 30 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Profhilo<br>The intradermal procedure was performed bilaterally on the face, at level of the following five points: zygomatic protuberance nostril's angle inferior margin of tragus lip marionette lines mandibular angle. The amount of product injected, was 0.2 ml for each injection-point. | Device: Profhilo<br> <br> * Other names: IBSA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wrinkle Severity Rating Scale (WSRS) improvement | Reduction of wrinkles severity corresponding to a decrease from the baseline of the Wrinkle Severity Rating Scale (WSRS) clinical score where: Grade 1 (absent): no visible nasolabial fold; continuous skin line. Grade 2 (mild): shallow but visible nasolabial fold with a slight indentation; minor facial feature. Grade 3 (moderate): moderately deep nasolabial folds; clear facial feature visible at normal appearance but not when stretched. Grade 4 (severe): very long and deep nasolabial folds; prominent facial feature; <2mm visible fold when stretched. Grade 5 (very severe): extremely deep and long nasolabial fold, detrimental to facial appearance; 2-4 mm visible V-shaped fold when stretched. | Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W). | 
| Facial Volume Loss Scale (FVLS) improvement | Reduction of face volume loss corresponding to a decrease from the baseline of the Facial Volume Loss Scale (FVLS) where Grade 1 Mild flattening or shadowing of one or more facial regions (including the cheek, temple, preauricolar and periorbital areas). No prominent bony landmarks. No visibility of underlying musculature. Grade 2 An intermediate point between grade 1 and grade 3. Grade 3 Moderate concavity of one or more facial regions (including the cheek, temple, preauricolar and periorbital areas. Prominence of bony landmarks. May have visibility of underlying musculature. Grade 4 An intermediate point between grade 3 and grade 5. Grade 5 Severe indentation of one or more facial regions (including the cheek, temple, preauricolar and periorbital areas). Severe prominence of bony landmarks. Clear visibility of underlying musculature. | 16 weeks | 
| Surface microrelief's regularity improvement | Improvement of skin surface microrelief corresponding to a reduction of the clinical score of microrelief's regularity grade where Grade 1:very regular, Grade 2: regular, Grade 3: irregular, Grade 4: very irregular. Clinical evaluation of surface microrelief's regularity grade is carried out on the digital picture acquired by FotoFinderDermoscope with a magnification of 20X | Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W). | 
| Determination of profilometric parameters | Reduction of the nasolabial fold and marionette lines profilometric parameters versus baseline where Ra is average roughness of the analysed profile, Rt is wrinkles total high, Rv is wrinkles maximum depth. Replicas of nasolabial fold and marionette lines are obtained using silicone rubber. A picture of the skin replicas is taken thanks to Primos compact portable device (GFMesstechnik); Primos software is able to elaborate 3D representations of skin wrinkles as well as to measure skin principal profilometric parameters. | Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W). | 
| Skin plastoelasticity improvement | Improvement of the principal torsiometric parameters Ue (immediate extensibility), Uf (final extensibility), Uv (viscoelasticity) and Ur (immediate elastic recovery).Skin firmness is measured with the instrument Dermal Torque Meter (Dia-Stron Ltd., UK). | Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W). | 
| Superficial skin hydration improvement | Improvement of skin electrical capacitance value measured with Corneometer CM825 (Courage - Khazaka, Köln, Germany). The measure of the skin capacitance properties is an indirect expression of its hydration level. | Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W). | 
| Deep skin hydration improvement | Improvement of tissue dielectric constant value of superficial and deep skin layers measured with MoistureMeterD (Delfin Technologies, Kuopio - Finland) | Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W). |