Objective:

The main aim of this trial was to assess safety and tolerability of tauroursodeoxycholic acid (TUDCA) supplementation in patients with progressive multiple sclerosis (pwPMS). Secondary objectives were to assess the effects on serum BA profile and clinical outcomes.

Background:

We have previously identified changes in the metabolome, specifically in bile acid (BA) metabolism in MS. We demonstrated that BA receptors are present in MS lesions, and TUDCA supplementation ameliorated disease in an animal model of MS and had direct anti-inflammatory effects on astrocytes and microglia. Trials in other neurodegenerative diseases have shown that TUDCA may be neuroprotective. The effects of TUDCA supplementation on MS are unknown but could provide a pathway for developing new therapies in PMS. 

Design/Methods:

In this randomized, double-blinded trial, pwPMS were enrolled and randomized 1:1 to either receive TUDCA (1 g twice daily) or placebo for 16 weeks. Clinical visits occurred at 0, 8, and 16 weeks. Primary outcomes were safety and tolerability of TUDCA. Secondary outcomes included changes in BA serum levels and clinical outcomes. 

Results:

Of the 59 participants enrolled, 47 (80%) completed >2 visits and were included in the analysis (21 in placebo arm, 26 in TUDCA arm). The number of participants reporting adverse events was not significantly different between groups (10 in TUDCA arm vs 7 in placebo arm; p=0.72). The TUDCA group demonstrated significant increases over time in levels of TUDCA (p<0.001), glycoursodeoxycholic acid (p<0.001), ursodeoxycholic acid (p<0.001), and lithocholic acid (p=0.02). There was a significant improvement in MSFC (p=0.03), while no change was noted in EDSS and MSQOL-54 mental or physical composites in the TUDCA arm; no significant changes were noted in these outcomes in the placebo arm.

Conclusions:

TUDCA supplementation was safe and tolerable in pwPMS, and led to significant increases in levels of several bioactive secondary BAs and improvement in MSFC score.