Effect of an Emollient Cream Containing a Milk Bioactive Peptide on Clinical Signs, Pruritus and Bacterial Colonization of Mild Atopic Dermatitis Skin Lesions in Pediatric Population (AD-GMP-SCORAD)

Universidad Autónoma de Aguascalientes

Status: Enrolling

Conditions: Atopic Dermatitis (AD)

Treatments: Other: glycomacropeptide; Other: emollient cream

Study type: Interventional

Funder types: Other

Identifiers

NCT07259343

COB-UAA/09/2024

PIBB26-2 (Other Grant/Funding Number)

Details and patient eligibility

About

The goal of this clinical trial is to evaluate the protective effect of glycomacropeptide on the clinical signs and symptoms of atopic dermatitis in children aged 2 to 12 years, and to determine if topical administration of glycomacropeptide is associated with a lower colonization by Staphylococcus species on the skin. The main questions that it aims to answer are:

• Does glycomacropeptide reduce the signs and symptoms related to atopic dermatitis in the pediatric population?
• Does glycomacropeptide modify the colonization of Staphylococcus species in atopic dermatitis lesions in the pediatric population? Researchers will compare an emollient cream containing glycomacropeptide with an emollient cream without glycomacropeptide to evaluate whether treatment with glycomacropeptide achieves a greater reduction in the clinical severity and pruritus of atopic dermatitis and a lower bacterial colonization compared with the exclusive use of emollients.

Participants will:

• Read and sign the informed consent
• Undergo a prick test at the first visit to ensure no reaction to the treatment components
• Receive the assigned treatment (glycomacropeptide cream or emollient cream), which must be applied twice daily only to atopic dermatitis lesions.
• Visit the clinic once a week for 4 weeks for follow-up and SCORAD assessments, and for skin sample collection by stripping at first and last visit.

Full description

Atopic dermatitis is a chronic and recurrent skin disease characterized by intense pruritus, dry skin, inflammation, and, in some cases, eczema. Although it can occur at any age, it is more common in childhood, with a global prevalence estimated between 5% and 20% in children, and approximately 7.3% in adults. Its impact on quality-of-life ranges from mild discomfort to significant sleep disturbances and limitations in daily activities.

The pathogenesis of atopic dermatitis is associated with structural and functional impairment of the epidermis, leading to inflammation, dysregulation of T helper cells (Th1/Th2), increased immunoglobulin E production, and mast cell hyperactivity, all of which exacerbate barrier abnormalities. The most common barrier defect is decreased production of filaggrin or other stratum corneum proteins, contributing to xerosis and increased susceptibility to infections. In addition, reduced production of antimicrobial peptides facilitates bacterial colonization.

Current treatment of atopic dermatitis relies on emollients, topical corticosteroids, and topical or systemic calcineurin inhibitors, depending on disease severity and persistence. However, prolonged use of these drugs can result in adverse effects such as burning, hypertrichosis, telangiectasias, skin atrophy, acne, folliculitis, contact dermatitis, nephrotoxicity, hepatotoxicity, seizures, and neoplasms. Therefore, there is a need for alternative treatments that can reduce quantity and time for drugs and promote patient recovery.

Glycomacropeptide is a 64-amino acid peptide derived from bovine casein during cheese production by chymosin or during milk digestion by pepsin. It is highly glycosylated, mainly at serine and threonine residues, with tetra-saccharides containing sialic acid as a key component of its bioactivity. Clinical studies have demonstrated the safety of oral glycomacropeptide in humans, and multiple biological activities have been described, including anti-inflammatory and anti-allergic effects in preclinical models of asthma, urticaria, food allergy, and atopic dermatitis.

About skin, glycomacropeptide has shown beneficial effects on keratinocytes, protecting them against apoptosis, inflammation, and oxidative stress, while promoting their migration and proliferation, processes that support skin repair in atopic conditions. Glycomacropeptide also inhibits mast cell and macrophage activation, key immune cells abundant in atopic dermatitis lesions that contribute to chronic inflammation.

Atopic dermatitis is associated with skin dysbiosis, characterized by reduced bacterial diversity and overgrowth of Staphylococcus aureus. In vitro studies from our laboratory demonstrate that glycomacropeptide does not promote the growth of S. aureus or Staphylococcus epidermidis. Instead, it inhibits S. aureus adhesion to human keratinocytes and, in contrast, enhances S. epidermidis adhesion, a commensal species that contributes to skin homeostasis. Furthermore, glycomacropeptide reduces the ability of S. aureus to form biofilms, a key persistence mechanism.

These findings support the potential of glycomacropeptide as a topical therapeutic candidate for atopic dermatitis, acting through modulation of inflammation, skin repair, and modulation of the microbiota.

This is a randomized, parallel, double-blind clinical trial. The primary objective is to evaluate the protective effect of topical glycomacropeptide on the clinical signs and symptoms of atopic dermatitis in children.

The secondary objectives are:

1. To determine whether topical glycomacropeptide is safe and well tolerated in children with atopic dermatitis.
2. To determine whether topical glycomacropeptide is associated with changes in the severity of atopic dermatitis lesions and the extent of eczema, based on the SCORAD index.
3. To determine whether topical glycomacropeptide decreases pruritus associated with eczema and improves sleep duration.
4. To determine whether topical glycomacropeptide is associated with reduced S. aureus colonization on the skin.

The main questions this study aims to answer are:

• Does glycomacropeptide reduce the signs and symptoms related to atopic dermatitis in the pediatric population?
• Does glycomacropeptide modify the colonization of Staphylococcus species in atopic dermatitis lesions in the pediatric population? Study Population. Children aged 2 to 12 years with a diagnosis of atopic dermatitis confirmed by the Hanifin and Rajka criteria, and classified as mild according to the SCORAD index (<25 points). Participants will be excluded if they fall outside the age range, present a SCORAD score >25, have concomitant dermatoses, a history of hypersensitivity or anaphylaxis to any treatment components, inability to attend follow-up visits or adhere to the treatment schedule, or any clinical condition deemed unsuitable by the investigator.

Data verification procedures will be implemented to ensure precision and consistency. The database will include predefined rules for ranges and logical consistency checks (for example, age 2-12 years, SCORAD <25 at inclusion). Data that fall outside the expected range or are inconsistent with other fields will be flagged for review and corrected or canceled, as the case may be.

Recruitment Strategy. Enrollment will be carried out through collaboration with local pediatric, allergy and immunology, and dermatology medical associations. Additionally, screening campaigns will be conducted in primary schools to identify potential participants, followed by guardian consent discussions.

Sample Size and Interventions. A total of 20 eligible participants will be randomly assigned into two groups:

1. Emollient cream with glycomacropeptide.
2. Emollient cream without glycomacropeptide (control). Both formulations will be applied topically to atopic dermatitis lesions twice daily for 4 weeks. Participants will attend weekly follow-up visits for clinical evaluation and SCORAD assessment. At the first visit, a prick test will be performed to rule out hypersensitivity to cream components. In addition, skin samples will be obtained by stripping at baseline and at the final visit to quantify colonization by Staphylococcus species.

Data dictionary for study variables:

The independent variables of the study include:

• Sex: Defined as morphological differences between male and female. It will be obtained from the clinical record and classified as male or female.
• Age: Defined as the time period between birth and participation in the study. It will be obtained from the clinical record and expressed in complete years, with an expected range of 2 to 12 years.

The dependent variables of the study include:

• Atopic dermatitis diagnosis: Defined as the presence of a chronic and recurrent skin disease, confirmed by fulfilling at least three major and three minor Hanifin and Rajka criteria. Classified as present or absent.
• Severity of atopic dermatitis: Defined as the objective and subjective clinical characteristics of the disease, measured using the SCORAD Index. Severity will be categorized as mild (<25), moderate (25-50), or severe (>50).
• Exacerbation: Defined as the increase or recurrence of symptoms after a symptom-free period, also measured by the SCORAD Index, and classified as mild, moderate, or severe according to the same cut-off points.
• Remission period: Defined as the duration of absence of symptoms of atopic dermatitis. It will be measured in days, based on clinical evaluations.
• Exacerbation period: Defined as the duration of symptom exacerbation. It will be measured in days, based on clinical evaluations.
• Colonization by S. aureus: Defined as the presence and quantity of this opportunistic gram-positive bacterium in atopic dermatitis lesions. It will be measured through skin stripping samples analyzed by culture or PCR, expressed as copies of S. aureus femA gene per ng of total DNA.
• Ratio of S. aureus to S. epidermidis: Defined as the relationship between a pathogenic species and a commensal species of the cutaneous microbiota. It will be measured through skin stripping samples analyzed by culture or PCR, expressed as the ratio of DNA femA gene copies (S. aureus/S. epidermidis).
• Prick test: Defined as a skin test that exposes mast cells to allergens to detect sensitization. It will be recorded as positive when a wheal of ≥3 mm larger than the negative control is observed, and negative otherwise.

Data Collection. A quality assurance plan will be implemented to ensure precision and completeness of the collected data. A pediatric allergologist and the principal investigator will supervise adherence to the protocol at each participant in all clinical evaluations, and laboratory procedures will be performed according to standardized protocols.

All missing, unavailable, or uninterpretable data will be recorded as "missing." Data inconsistencies or out-of-range results will also be considered missing. The primary analysis will use the available data without imputation. Data will be analyzed using Prism GraphPad software, applying appropriate statistical methods according to the variables of interest.

All study records will be available for review by the ethics committee or external auditors if required.

Data Analysis. The statistical analysis will include descriptive statistics to summarize baseline characteristics of participants, including means, standard deviations, frequencies, and percentages, as appropriate. Comparisons between study groups will be performed using Chi-square tests. Continuous variables, including SCORAD index scores, bacterial colonization (S. aureus load and S. aureus/S. epidermidis ratio), and clinical outcomes such as duration of remission and exacerbation periods, will be compared between groups using Student's t tests. Statistical significance will be set at p < 0.05, and analyses will be conducted using Prism GraphPad software.

Final Report and Dissemination. Based on the results, a final study report will be prepared and a scientific manuscript will be drafted for potential publication.

Enrollment: 20 estimated patients

Sex: All

Ages: 2 to 12 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Children aged between 2 and 12 years.
• Clinical diagnosis of atopic dermatitis according to Hanifin and Rajka criteria.
• Mild atopic dermatitis with SCORAD <25 points.
• Written informed consent signed by parents or legal guardian.

Exclusion criteria

• Age younger than 2 years or older than 12 years.
• Moderate to severe atopic dermatitis (SCORAD >25 points).
• Presence of other dermatoses in addition to atopic dermatitis.
• Background of hypersensitivity or anaphylaxis to any components of the vehicle cream.
• Allergy or hypersensitivity to glycomacropeptide.
• Inability to attend follow-up medical consultations or to adhere to the treatment schedule.
• Any clinical reason determined by the clinical investigator that makes the child unsuitable for the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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20 participants in 2 patient groups

Topical administration of an emollient cream formulated with glycomacropeptide

Experimental group

Description:

Topical administration of an emollient cream formulated with 5% glycomacropeptide, applied twice daily for 4 weeks, restricted to affected skin areas, in pediatric patients with atopic dermatitis

Treatment:

Other: glycomacropeptide

Topical administration of the emollient cream formulated without glycomacropeptide

Active Comparator group

Description:

Topical administration of the emollient vehicle cream without glycomacropeptide, applied twice daily for 4 weeks to affected skin areas, in pediatric patients with atopic dermatitis

Treatment:

Other: emollient cream