Clinical trial NCT06925386: The Relationship Between Microbioma Balance and Acne Vulgaris as a New Acne Treatment
Official title: The Relationship Between Microbioma Balance and Acne Vulgaris as a New Acne Treatment
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Acne Vulgaris
Lead sponsor: Universitas Padjadjaran
Sponsor class: OTHER
Collaborators: name: PT. Prodia Stem Cell Indonesia
name: B-Crobes Laboratory (M) Sdn Bhd
First posted: 2025-04-13
Enrollment: 64
Sex: ALL
Minimum age (years): 13
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A parallel group design with four arms was used, (1) standard therapy with oral probiotics and topical secretome (placebo), (2) standard therapy with oral probiotics (placebo) and topical secretome, (3) standard therapy with oral probiotics and topical secretome, and (4) standard therapy with oral probiotics (placebo) and topical secretome (placebo). Participants were assigned to groups using a random permuted block sampling method (comprising A, B, C, D). This method is commonly applied in clinical trials including small sample sizes with staggered participants' enrollment. Observation spans 8 weeks. All groups were subjected to pretest and posttest assessments, measuring acne severity, fecal microbiome metabolites, skin condition, and IL-6 before and after intervention.
Primary purpose: TREATMENT

Brief summary: Background: Acne vulgaris is a chronic inflammatory condition primarily caused by Cutibacterium acnes, which disrupts skin homeostasis, thereby triggering immune responses and sebum metabolism. Dysbiosis is an imbalances in the skin and gut microbiota identified as a significant factor contributing to acne progression. Standard therapy often rely on antibiotics, but the long-term use has increased antibiotic resistance, including in Indonesia. Consequently, alternative methods, such as probiotics and mesenchymal stromal cell (MSC) secretomes are gaining attention for immunomodulatory and regenerative properties. These novel therapies have shown promising results in modulating the skin and gut microbiota while reducing inflammation.

Study Design: A phase 2 double-blind randomized controlled trial was adopted using a parallel group design with four arms, namely: (1) standard therapy with oral probiotics and topical secretome (placebo), (2) standard therapy with oral probiotics (placebo) and topical secretome, (3) standard therapy with oral probiotics and topical secretome, and (4) standard therapy with oral probiotics (placebo) and topical secretome (placebo). Sixty-four mild to moderate acne vulgaris patients were randomly allocated to these groups. Interventions were administered over a period of 8 weeks, with outcomes measured at baseline and post-therapy. This study was conducted at Dermatology and Venereology Department of Bali Mandara General Hospital (RSBM). The primary outcome is the reduction of comedones and inflammatory lesions, assessed using the Yolov8 method. Secondary outcomes include gut and skin health parameters, such as tryptophan metabolites, collagen, pH, moisture, sebum levels, and IL-6, to explore the relationship between microbiome balance, skin condition, and inflammation in acne.

Discussion: In the context of increasing antibiotic resistance in Indonesia, where therapies often fail to produce sustainable clinical outcomes, this study showed the potential of combining probiotics and MSC secretomes as adjunctive therapies for acne vulgaris. Probiotics restored gut and skin microbiota balance, while MSC secretomes promoted immune modulation and tissue repair. The results of this study paved the way for innovative, non-antibiotic methods for acne management, addressing the need for sustainable and effective therapies amidst growing concerns over dysbiosis and antibiotic resistance.

Detailed description: Acne cases have a very high number of visits to doctors, around 87%, especially in teenagers, which has implications for the psychological impact where long treatment with repeated inflammation for quite a long time can have the effect of reducing self-confidence and increasing stress. The therapy that is often given to Acne vulgaris is in the form of long-term topical antibiotics which can risk increasing the bacteria's resistance to antibiotics. Researchers are considering a new therapeutic approach in improving acne vulgaris by improving the balance of the microbiome through consuming oral probiotics so that it can reduce the development of C. acnes bacteria that cause acne and administering serum containing secretome to reduce inflammation/lesions in acne. As proof of the effect of the addition of this new therapy, research was carried out which required 64 research participants who met the criteria and consent from research participants was indicated by agreeing to take part in the research as outlined in the informed consent and research participants were asked to be involved until the research was completed. In research involving humans (participants) who experience mild to moderate acne as determined through examination by a dermatologist to determine the severity of the acne (seen from the total number of acne lesions or bumps), the patients included in the study had an age range of 13 - 45 years, and additional criteria such as: experiencing new acne lesions or bumps repeatedly in the last 6 months, willing to have flash facial images, and physically and mentally healthy. Research participants were given additional therapy from the therapy that should have been given by a doctor. The additional therapy was in the form of oral probiotics which had BPOM distribution permits and topical secretome in the form of facial serum. Participants will be divided into 4 groups randomly so that respondents are selected fairly and objectively. All drugs/test materials use natural ingredients which tend to be very safe with low side effects, oral probiotics have been reported in a few cases with diarrhea and secretome side effects with a very low possibility of skin redness, but to further increase safety, researchers will carry out a skin redness test first. first on the skin before being given the test material, and if changes occur such as loose stools and repeated bowel movements more than 3 times a day, the researchers have prepared medication as a preventive measure, and if it continues, it will be fully handled by the researchers. The development of new therapies, especially skin diseases, in this case Acne vulgaris, needs to be explored, one of which is through the microbiome approach and new regenerating medicine using stem cells (secretome). In this study, researchers want to prove that natural ingredient-based treatments, namely oral probiotics and topical secretome, can have the potential to improve acne vulgaris through measuring microbiome balance and severity, so in this study a clinical trial will be carried out to compare the effects of standard therapy (usual therapy) with additional oral probiotic therapy and topical secretome on its ability to increase clinical and microbiome improvement in moderate-severe Acne vulgaris patients through a double-blended open label Randomized Control Trial study.

Eligibility criteria: Inclusion Criteria:

* individuals aged 13 to 45 years
* diagnosed with acne vulgaris by a certified dermatologist, presenting with mild to moderate facial acne based on the lesion count criteria by Lehman et al. Mild acne is defined as having fewer than 20 comedones or fewer than 15 papular/pustular lesions, while moderate acne is characterized by 20-100 comedones and 20-50 papular/pustular lesions.
* must have experienced recurring new acne lesions in the past 6 months
* must be willing to comply with all protocol requirements
* must be willing to have standardized facial photograps taken using an imaging system
* must be able to follow study and adhere to a fixed schedule
* must have ability to provide inform concent for participation in the study
* must be generally healthy and in good mental condition.

Exclusion Criteria:

* pregnant patients
* subjects who have undergone hormonal acne treatment within six months prior to the study
* subjects who have taken oral isotretinoin within one month prior to the study.
* simultaneous participation in a different study conducted by an external research institution at the same testing site.
* inadequate language proficiency (both spoken and written)
* participation in the study under the influence of alcohol and/or drugs, as well as substance addiction
* severe diseases (cardiovascular, hepatic, renal, or pulmonary diseases, severe diabetes mellitus) or chronic infections (Hepatitis, HIV).
* immunodeficiency.
* current use of the following topical or systemic medications: corticosteroids, immunosuppressants, and antihistamines.
* skin conditions such as vitiligo, psoriasis, or atopic dermatitis.
* any other diseases or medications that may directly interfere with the study or pose a risk to the subject's health

Primary outcomes:
measure: Reduction of comedones and inflammatory lesions
timeFrame: From enrollment to the end of treatment at 8 weeks
Secondary outcomes:
measure: Tryptophan metabolites
timeFrame: From enrollment to the end of treatment at 8 weeks
measure: Inflammatory Response
timeFrame: From enrollment to the end of treatment at 8 weeks
measure: Collagen Measurement
timeFrame: From enrollment to the end of treatment at 8 weeks
measure: Moisture content
timeFrame: From enrollment to the end of treatment at 8 weeks
measure: Sebum levels
timeFrame: From enrollment to the end of treatment at 8 weeks
measure: pH levels
timeFrame: From enrollment to the end of treatment at 8 weeks
Other outcomes:
Locations:
city: Denpasar
country: Indonesia
facility: Rumah Sakit Umum Daerah Bali Mandara
state: Bali
Study officials:
References: