Clinical trial NCT04056598: Acne Vulgaris Related Microbiology and Serology
Official title: Characterization of Immune Responses Against Acne-associated Bacterium Propionibacterium Acnes - a Pilot Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acne Vulgaris
Keywords: P. acnes
acne vulgaris
humoral immune response
microbiome
SLST
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: CRAT
First posted: 2019-08-14
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects for the study will be drawn from:

* Study group: Acne patients, 18-40 years of age, currently suffering from moderate or severe acne vulgaris
* Control group: Healthy individuals of 18-40 years of age, who recovered from moderate or severe acne vulgaris

Brief summary: This will be an investigation to determine the quality of the serological immune responses against Propionibacterium acnes (P. acnes) in acne patients compared to healthy individuals. In particular, the investigators will measure serum antibody titers against P. acnes surface antigens, and the efficiency of antibody-mediated phagocytic killing of P. acnes.

Detailed description: Acne vulgaris, which affects \>85% of teenagers and \>10% of adults, was recently re-defined as a complex chronic disease associated with Propionibacterium acnes (P. acnes). Until recently, the pathogenic role of bacteria Propionibacterium acnes (P. acnes) has been debated due to the fact that this bacterium is also found, although in lower density, on the skin of healthy individuals. However, in the last few years, genomic sequencing and the comparative analysis of \>250 P. acnes strains revealed the existence of the strains prevalently associated with severe cases of acne. In the study that analyzed more than 200 clinical isolates, it was found that 75% of the P. acnes strains that were isolated from acne lesions of acne patients, belonged to genetic type I-IA and that this group also represented 85% of the antibiotic resistant P. acnes strains isolated in the course of the study. This provided the first clear evidence for the virulent potential of P. acnes, that has been previously suspected also in some cases of eye, bone and post-operative infections. More recent research studies have identified additional virulent strains which can be distinguished based on the ribosomal DNA analysis.

Although these genetic studies have revealed the existence of virulent P. acnes strains, it is not yet clear how these strains promote disease pathogenesis and symptoms, and whether the host immune response either exaggerates or ameliorates the disease. In particular, there have been no systematic studies regarding the role of a central immunity in the protection against this pathogen.

Therefore, this will be one of the first studies to address scientifically and therapeutically important questions including:

1. Immunogenicity of P. acnes in the acne patients compared to healthy individuals who are recovered from moderate or severe acne vulgaris.
2. The role of antibodies in controlling colonization and acne development due to P. acnes
3. The relationship between P. acnes genetic information and serotype classification, based on the immune recognition pattern (the degree of the similarity among genetically different strains based on the surface components recognition by the immune system) Answering these questions could support development of novel and better treatment options, which could significantly improve the outcome in acne vulgaris patients. Existing acne treatments either treat the symptoms only on skin surface (e.g. topical agents: creams, lotions), or are not offering long-term solutions (antibiotics, vitamin A derivatives). Moreover, antibiotics raise antibiotic resistance among P. acnes as well as other types of bacteria and increase the risk of super-infection by other pathogens. Vitamin A derivatives are not effective in all patients and post-therapy relapse is common; besides, they are not routinely prescribed to patients due to serious side effects.

Eligibility criteria: Inclusion Criteria:

* Acne patients (18 - 40 years of age)
* Clinical diagnosis of medium acne vulgaris (covering more than 30% of the patient's face and loaded with comedones, pustules and acne lesions of \>2 cm in size) for at least six months or longer
* Clinical diagnosis of severe acne vulgaris (acne conglobata, sinus or cystic type acne covering most of the face (\>60% of the facial surface) - IGA 3-4) for at least six months or longer
* Age-matched healthy adults (between 18 and 40 years), with history of moderate or severe acne, but who have been free from acne for more than two years - 'free from acne' period may include minor, intermittent breakouts due to hormonal reasons, such as menstruation

Exclusion Criteria:

* Subjects who received anti-acne antibiotic therapy less than 2 months prior to recruitment
* Subjects who received isotretinoin therapy within the last 6 months
* Subjects who were using hormonal contraceptives within the last 3 months

Primary outcomes:
measure: Correlation of acne vulgaris severity with humoral immunity assessed by ELISA, binding to P. acnes strains and OPK assay
timeFrame: Serum samples will be collected at visit and samples will be investigated upon availability of all samples. Analysis will occur an average of 1 year and will reflect patient's immune status at visit.
measure: Correlation of acne vulgaris severity with skin microbiome identified in acne lesions and by facial swabs
timeFrame: Swabs will be collected at visit and samples will be investigated upon availability of all samples. Analysis will be done an average of 1 year and will reflect patient's microbiome (on skin and in acne lesions) at visit.
Secondary outcomes:
measure: Correlation of microbiome identified on skin and acne lesion samples (Outcome 2) with humoral immunity (Outcome 1)
timeFrame: Serum and microbiome samples will be collected at patient's visit. Analysis will be done an average of 1 year and will reflect patient status at visit.
Other outcomes:
Locations:
city: Norfolk
country: United States
facility: Clinical Research Associates of Tidewater
state: Virginia
Study officials:
References: