Clinical trial NCT06321770: Oral Supplementation With Active Collagen Peptides and Skin Health Improvement
Official title: Oral Supplementation With Low Molecular Weight Collagen Peptides Improves Facial Wrinkles and Skin Hydration: Results From a Six-Week Randomized, Double-Blind, Placebo-Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Facial Wrinkles
Skin Hydration
Keywords: low molecular weight collagen peptides
aging
skin health
wrinkles
moisturization
elasticity
nutraceutical
randomized controlled trial
Lead sponsor: Gala Servicios Clinicos S.L.
Sponsor class: OTHER
First posted: 2024-03-20
Enrollment: 80
Sex: FEMALE
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blind, Placebo-Controlled Study
Primary purpose: TREATMENT

Brief summary: The present study aims to investigate the efficacy of daily supplementation with COLLinstant® LMW over a 6-week period in improving visible signs of aging. This in-cludes assessing its impact on skin wrinkle reduction, as well as its potential to en-hance skin elasticity and moisturization. COLLinstant® LMW was administered orally in a single-center, randomized, double-blind, placebo-controlled clinical trial. A sec-ondary objective involves comparing skin improvement, product satisfaction, and monitoring adverse events among middle-aged female volunteers.

Detailed description: Study design and ethical aspects This was a 6-week, prospective, randomized, placebo-controlled, double-blind, monocentric study performed at GALA Laboratories in Don Benito-Villanueva (Badajoz, Spain).

Participants were individually randomized (1:1 ratio) to a strategy of receiving either COLLinstant® LMW (collagen group) or a placebo regimen and followed up for 6 weeks. Subjects were instructed to dose both product regimens as per the manufacturer's package instructions or, when appropriate, investigator guidance.

The investigation was performed according to the ethical guidelines detailed in the Declaration of Helsinki (amendment of the 64th General Assembly, Fortaleza, Brazil, October 2013) and with national regulations of Spain, and in full compliance with the applicable principles of good clinical practice (GCP) and International Council for Harmonisation (ICH) of Technical Requirements for Pharmaceuticals for Human Use. The trial protocol was approved (code 075-2022) by the Clinical Research Ethics Committee at the University Hospital of Cáceres (Caceres, Spain) and written informed consent was obtained from all subjects prior to any study procedures being ini-tiated.

Intervention/study products The test product is classified as a food supplement. The preparation under study was COLLinstant® LMW (Viscofan DE GmbH, Weinheim, Germany), an oral food supplement based on bovine bioactive hydrolyzed type I and III-collagen peptides.

Following ICH-GCP requirements and applicable local regulations, the inves-tigational product and placebo were presented as a powder for oral suspension and sealed in sachets that were identical in appearance and odor.

Each sachet of the active COLLinstant® LMW contained low molecular weight hydrolyzed 2.5 g collagen peptides. Other ingredients, which were also contained in the placebo, were 467 mg lemon flavour, 150 mg citric acid, 8.5 mg sucralose and 7.1 mg stevia (97%). The placebo did not contain any nutrients.

Study subjects We recruited a total of 80 women (aged 30-65 years) with phototypes I-IV, who were mentally and physically healthy, had a BMI 20.0-29.9 kg/m2 and displayed visible signs of natural and photoaging on their face (crow´s feet) rated from moderate to se-vere \[21\].

The Fitzpatrick scale is a numerical classification for human skin color (in a scale of I-VI), with the amount of melanin in the skin indicating the type of skin, its suscep-tibility to burns and its ability to tan.

During the screening phase, the participants satisfied all inclusion and exclusion criteria and agreed to avoid prolonged exposure to ultraviolet (UV) radiation for the duration of the study.

Subjects were excluded in case of pregnancy, lactation, acute or chronic skin dis-ease or dermatological disorder; use of natural health supplements for improving the skin within 1 month before the start of the study; low protein diet; planned or una-voidable exposure to UV radiation; tattoos on or near the test area; use of systemic cor-ticosteroids or applied topical alpha hydroxyl acids near the test site within 4 weeks of enrolment; use of topical medications near the test area within 6 weeks of enrolment; Botulinum toxin A (Botox) treatment or filler injection (collagen, hyaluronic acid, etc) near the test sites within 2 years of enrolment; subjects cognitively impaired and/or unable to give informed consent; or had any other condition which in the medical in-vestigator's opinion may adversely affect the individual's ability to complete the study or its measures or which may pose significant risk to the individual.

Study schedule and biometric evaluation All participants (test and placebo group) were instructed to consume the content of one sachet daily, in the morning, on an empty stomach for 6 weeks. It was required that the product was dissolved in at least 100 ml of water, juice or other liquid.

For all women participating in the study, biometric characteristics were assessed at baseline (T0), and after 6 weeks of treatment with the products (T6).

Measurement of skin wrinkling parameters (volume, area and depth) was evalu-ated at the crow's feet region and changes were analyzed and digitally photographed in all patients by VisioFace® 1000D (equipped with a high-resolution reflex camera).

Afterwards, subjects were acclimatized for at least 30 min in the air-conditioned measurement room at a temperature of 21 ± 1°C and a relative humidity of 50 ± 5 %.

Skin elasticity was measured at the crow's feet region, so a Cutometer® dual MPA 580 (Courage \& Khazaka) was used to assess skin biomechanical properties. This non-invasive tool evaluated the skin elasticity by negative force that distorts the skin mechanically. The functional principle is based on suction of the skin using a probe with negative pressure (450 mbar), which causes the test area to be drawn into the ap-erture of the probe. A non-contact optical measuring system determined the penetra-tion depth of the skin. The parameters evaluated were R0, R2, R5, R7 y R9 and measurements were carried out in triplicate.

R0 represents the final distension of the first curve i.e., the passive behavior of the skin to the suction force and correlates to the skin firmness. This parameter is meas-ured from the highest point of amplitude at the end of the suction phase to the baseline reading (R0 = Uf).

The R2 parameter is related to the gross elasticity/ viscoelasticity, which is the skin's resistance to the mechanical suction force versus its ability to recover (R2 = Ua/Uf).

R5 refers to net elasticity and is represented by the ratio of the elastic portion of the suction stage to fast recovery throughout relaxation stage (R5 = Ur/Ue), meaning the higher the value, the more elastic the skin. R7 is related to biological elasticity. R7 is the immediate elastic recovery in the first 0.1 s compared with the amplitude (total deformation) after suction (R7 = Ur/Uf) and can be interpreted as another marker of elasticity, with aging causing its reduction; and R9, the residual deformation at the end of the measuring cycle, indicating the tiring effects or fatigue of skin after repeated suction (R9 = R3 - R0).

In addition, measurement of stratum corneum hydration was performed at each study visit by the electrical capacitance method using a Corneometer® CM 825 (Courage \& Khazaka, Cologne, Germany). At least five determinations per measure-ment area at four different locations (middle forehead, both right and left cheek bone and the chin area) were performed, then the average was used for analysis.

Self-reported measures After 6 weeks of treatment, the volunteers filled out questionnaires, to subjectively assess their perception of different parameters such as efficacy, organoleptic properties and satisfaction since the last time they took the product. The Spanish version of the Treatment Satisfaction Questionnaire with Medication (TSQM), and a 3-point Likert scale with the following items: Dissatisfied, slightly satisfied and very satisfied, were used.

Eligibility criteria: Inclusion Criteria:

* Women (aged 30-65 years) with phototypes I-IV, who were mentally and physically healthy, had a BMI 20.0-29.9 kg/m2 and displayed visible signs of natural and photoaging on their face (crow´s feet) rated from moderate to severe

Exclusion Criteria:

* Pregnancy, lactation, acute or chronic skin disease or dermatological disorder; use of natural health supplements for improving the skin within 1 month before the start of the study; low protein diet; planned or unavoidable exposure to UV radiation; tattoos on or near the test area; use of systemic corticosteroids or applied topical alpha hydroxyl acids near the test site within 4 weeks of enrolment; use of topical medications near the test area within 6 weeks of enrolment; Botulinum toxin A (Botox) treatment or filler injection (collagen, hyaluronic acid, etc) near the test sites within 2 years of enrolment; subjects cognitively impaired and/or unable to give informed consent; or had any other condition which in the medical investigator\&#39;s opinion may adversely affect the individual\&#39;s ability to complete the study or its measures or which may pose significant risk to the individual.

Primary outcomes:
measure: Skin wrinkling volume (px^3)
timeFrame: 6 weeks
measure: Skin wrinkling area (px^2)
timeFrame: 6 weeks
measure: Skin wrinkling depth (px)
timeFrame: 6 weeks
measure: R0= Skin firmness (mm)
timeFrame: 6 weeks
measure: R2= gross elasticity (%) of the skin
timeFrame: 6 weeks
measure: R5= Skin net elasticity (%)
timeFrame: 6 weeks
measure: R7= Skin elastic recovery (%)
timeFrame: 6 weeks
measure: R9= Skin fatigue (mm)
timeFrame: 6 weeks
measure: Skin hydration (AU)
timeFrame: 6 weeks
Secondary outcomes:
measure: Subjective perception of product efficacy
timeFrame: At (T6), six weeks after the trial began
measure: Subjective perception of the organoleptic characteristics of the product
timeFrame: At (T6), six weeks after the trial began
measure: Opinion on the degree of satisfaction with the product
timeFrame: At (T6), six weeks after the trial began
Other outcomes:
Locations:
city: Don Benito
country: Spain
facility: GALA Laboratories
state: Badajoz
Study officials:
affiliation: University of Extremadura
name: Juan Antonio Carrillo
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Extremadura
name: Rafael Guerrero
role: PRINCIPAL_INVESTIGATOR
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