Effects of Uro-Vaxom vs. placebo on the urinary tract microbiome in individuals with spinal cord injury in a randomized controlled pilot trial (Uro-Vaxom pilot)

Abstract

Individuals with spinal cord injury/disease (SCI/D) have a high incidence of urinary tract infections (UTI). This randomized controlled pilot trial investigated the effect of an immunomodulator (Uro-Vaxom) versus a placebo on the urinary tract microbiome of individuals with SCI/D to inform the design of a larger trial. Twenty participants with SCI/D undergoing primary rehabilitation were randomized to receive either Uro-Vaxom or a placebo for three months (ClinicalTrials.gov NCT04049994 08/08/2019). Urine was collected at baseline, immediately post-treatment, and three months post-treatment. DNA was extracted and sequenced using full-length 16 S rRNA using Oxford Nanopore technology. Internal controls were added for absolute abundance estimation. There were 10 participants in Uro-Vaxom and 10 in placebo analyzed. The prevalence of Escherichia coli was lower in the Uro-Vaxom group (2/10) compared to the placebo group (5/10) post-treatment, although this difference was not statistically significant. Significant alpha and beta diversity differences were associated with the microbial load, sex, and voiding method. Uro-Vaxom showed potential in reducing E. coli prevalence during the treatment period, but this result requires validation in a larger trial. Future trials should consider the baseline microbial load and optimal timing of intervention to ensure that the observed effects are attributable to immunomodulation.

Keywords: Full length 16S rRNA; Immunomodulation; Spinal cord injury; Urinary tract infections; Uro-Vaxom.

Fig. 1

Flow diagram of the Uro-Vaxom pilot as per consolidated standards of reporting trials (CONSORT) 2010 guidelines.

Fig. 2

Summary of the microbial load and relative abundance profile of the urinary tract microbiome of individuals with SCI who participated in the pilot randomized control trial on Uro-Vaxom versus placebo (a) and the time in weeks to develop the first UTI among the trial participants with their baseline microbial load and dominant organisms in urine (b).

Fig. 3

Alpha (a) and beta diversity (b) differences in microbial load in participants’ urine and the summary of the differences in the beta diversity and the differential abundance results for E. coli when the threshold for bacteriuria is scaled up by magnitude (c).

Fig. 4

Summary of the comparisons of the beta diversity between sexes (a), the differential abundance results of the three most prevalent Lactobacillus species identified between sexes (b), and the heat map of the log₁₀ absolute abundance of the Lactobacillus species identified in relation to the presence of an Enterobacteriaceae (c).

Fig. 5

Summary of the alpha (a) and beta (b) diversity differences between voiding methods, with the most prevalent differentially abundant species (c).