Clinical trial NCT04548349
Conditions: Acne Healthy
Sponsor: Beth Israel Deaconess Medical Center
Start date: 2021-04-23; Completion date: 2022-08-22
Enrollment: 25 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The study objective is to characterize the shift in the diversity and abundance of the skin microbial community at baseline and in response to Altreno monotherapy as compared to benzoyl peroxide (BPO) 2.5% leave-on gel monotherapy in acne patients.

Detailed description:
With the advent of 16S rRNA sequencing, scientific community is beginning to understand the critical importance of the microbiome in human health. In dermatology, researchers have begun to lead the effort to not only better understand how the microbiome contributes to the pathogenesis of skin disease, but also harness its power to develop novel therapies. Acne is a common inflammatory skin disorder. P. acnes on the skin has been traditionally thought of as the culprit bacteria in the pathogenesis of acne.

Recent studies demonstrate that the skin microbial composition dynamically changes in response to systemic acne therapy. Using 16 rRNA gene sequencing, a prior study has confirmed that systemic antibiotic treatment decreased the abundance of P. acnes, which returned to baseline after discontinuation of the therapy. In contrast, the systemic therapy increased the abundance of Pseudomonas species, which returned to baseline after therapy cessation. Based on the opposing response to the therapy, it can be speculated that these two species compete for the same microenvironment within the skin microbiome. Interestingly, the same systemic therapy decreased the abundance of lactobacillus genus, the "good bacteria" that is protective against skin infection, and that decrease was sustained even after cessation of the therapy. Similarly, another study has demonstrated that systemic isotretinoin therapy disturbed the skin microbiome in acne patients with increased bacterial diversity on the cheeks. It is unclear the potential therapeutic role of the increased bacterial diversity in the management of acne patients.

The study aims to characterize the shift in the diversity and abundance of the skin microbial community in response to Altreno in acne patients. Understanding the role of the skin microbiome in response to therapy can help clinicians to develop tailored, targeted treatment options, including reconstitution of "good bacteria." Furthermore, it can lead to development of novel topical pre and probiotics.

Arms: arm 1: None arm 2: None arm 3: During the entire study period, the subjects in the control group will not be allowed to use any antibacterial wash, other than approved OTC cleansers.
Interventions: intervention 1: Altreno intervention 2: Benzoyl peroxide
Intervention descriptions: intervention 1: Acne patients will be assigned to Altreno once daily. intervention 2: Acne patients will be assigned to BPO leave-on gel once daily.

Protocol documents:
Prot_SAP_001.pdf: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Profiling the Skin Microbiome in Response to Altreno in Acne Patients 
NCT #: 04548349 
Document Date: June 15, 2020 
 


Study Design 
 
This is a single-center, prospective study. 
 
Study Population 
 
Up to 60 subjects who meet study inclusion/exclusion criteria will be recruited into the study. 
 
Materials and Methods 
 
We will prospectively recruit healthy controls and acne patients from the BIDMC 
dermatology clinic as follows: 
 
• Control Group: We will recruit up to 20 healthy controls without any skin diseases. 
• Experimental Group: We will recruit up to 40 patients with acne with severity that 
warrants initiation of a topical medication and randomize 20 patients into Altreno 0.05% 
lotion monotherapy (applied once daily) and 20 patients into BPO 2.5% leave-on gel 
monotherapy (applied once or twice daily as tolerated). 
 
Control Group will undergo skin swab at baseline and approximately 120 days later without 
any intervention. During the entire study period, the Group will not be allowed to use any 
antibacterial wash, other than approved OTC cleansers. *If due to the pandemic, subjects 
cannot return for 2nd visit in 120 days, the subjects will still remain in the study until able to 
do so.  
 
Experimental Group will undergo skin swab at baseline, as well as clinical scoring of acne. 
Then, they will be prospectively divided 1 to 1 into Altreno group or BPO group. During the 
following 90 days, the Group will only be allowed to use either Altreno or BPO. On the 
second visit (90 days +/- 5 days), their acne will be scored again, and repeat skin swab will 
be taken. If significant improvement, they will be asked to discontinue the therapy for 30 
days. If no significant improvement, they will be instructed to continue the therapy for 
additional 30 days. On the third visit (120 days +/- 5 days from the first visit), their acne will 
be scored, and repeat skin swab will be taken. *If due to the pandemic, subjects cannot 
return for subsequent visits, the subjects will either continue the therapy (or continue without 
therapy) and remain in the study until able to return for the subsequent visits.  
 
All skin swab samples will be stored at -80 °C until further processing. CoreBiome will 
receive skin swabs (with subject ID only, no other PHI), they will extract DNA, and perform 
16S rRNA gene and/or shotgun metagenomic sequencing. Corebiome will send the BIDMC 
research team the raw data. The research team will be doing the bioinformatics/analysis, 
not CoreBiome. If, after sending the skin swabs, subject withdraws, then the PI will ask 
Corebiome to destroy the sample and they will not perform DNA extraction or 16S 
rRNA/shotgun metagenomic sequencing. 
 
 
 
 


 
 
 
Data Analysis 
 
Primary Study Parameter(s): The primary outcome of this study is assessing for changes 
in skin microbial composition in acne patients after treatment with Altreno or BPO by 
specifically comparing their skin microbiomes (1) at baseline, (2) after 3 months of 
treatment, and (3) 1 month 10 after discontinuation of treatment. Comparisons of species 
diversity and relative abundance of the identified species will be made across healthy 
controls, Altreno group, and BPO group. 
 
The raw sequencing data will be first processed into taxonomic features using the 
standardized DADA2 protocol as implemented in the bioBakery. Then, we will analyze the 


three available microbial features (taxa, alpha diversity summary statistics, and community 
structure via beta diversity) across the three groups defined above. 
 
Secondary Study Parameter(s): The clinical severity will also be correlated to the 
presence and/or dominance of P. acnes and other populations using the following 
measures: 
 
• Physician Global Assessment of Acne: Categorical variable. A chi-square test will 
be performed for analysis. 
• Leeds Acne Score: Ordinal variable. A correlation analysis and depending on 
distribution, one-way ANOVA, a Kruskal Wallis or a Wilcoxon rank sum test will be 
performed for analysis. 
 
Other Study Parameter(s): Patient characteristics and demographics data will be 
presented using descriptive statistics. At every visit, adverse events and changes in 
medications will be registered. 
 
Statistical Analysis Plan (per Diversigen, who performed computational analysis) 
 
“To examine differences in abundance for taxa between treatment groups and across 
time, we examined taxa abundances at the Phylum, Family, Genus and ASV levels using 
the ASV count table as inputs. At each level of interest, count abundances were 
aggregated then transformed using the centered log ratio (CLR) transformation as 
implemented in the ALDEx2 R package. Briefly, transformation was performed using the 
aldex.clr() function, which estimates sequencing technical variation using Monte-Carlo 
sampling (n = 128) and generates CLR-transformed tables for each instance. A median 
CLR value for each taxon across all MC instances calculated and used for downstream 
plotting purposes.  
 
Next, we performed differential abundance testing using LME models of the following 
model:  
 
• taxon_abundance ~ Treatment_Cohort*Timepoint + (1|SubjectID) 
 
Pairwise contrast p-values for all relevant Treatment_Cohort and Timepoint comparisons 
were extracted from the model using emmeans(). Next, p-values were corrected for 
multiple hypothesis correction across all taxa tested using the FDR method. Finally, all 
adjusted p-values generated by testing were averaged across all 128 MC instances to 
obtain a padj value for each taxon for each pairwise comparison of interest.  
 
Using our standard significance thresholds of padj < 0.05, we found no taxa as 
significantly different in abundance at any level in any of the pairwise comparisons we 
examined. Therefore, we relaxed our threshold to padj < 0.2, which is less conservative 
but has been reported in the literature. Under this threshold, we found a few taxa that 
were significantly different.”