As of April 1, 2024, we found a new phase 3 trial that reportedly showed no benefits https://www.tudca.eu/top-line-results-announcement/. We therefore change our TOE “Trials” Grade from A to F.”
Since our last update, 2 ALS reversals in association with TUDCA (and other products) have been independently verified. We thus change our “Cases” grade from D to B.
Since our 2014 review there have been 2 important new clinical trials. A 2015 trial randomized 34 PALS to either TUDCA 1 gram twice daily or placebo for 54 weeks. Those on TUDCA had significantly slower progression on the ALSFRS-R score compared to those on placebo. TUDCA was well tolerated with only mild, mainly GI side effects (Eur J Neuro2016 Jan;23(1):45-52). A trial published in late 2020 randomized 137 PALS to AMX0035 (a combination of TUDCA and sodium phenylbuterate) or placebo for 24 weeks. Those on AMX0035 had statistically significantly slower progression on the ALSFRS-R score compared to those on placebo. AMX0035 was well tolerated, with rare, mild, mainly GI side effects (NEJM 2020;383:919-930). Based upon this new information we change our “Trials” grade to “A” and our “Risks” grade to “B.” We change our conclusion as well. “For PALS who want to self experiment, we now believe TUDCA to be a reasonable option for them to discuss with their doctors.”
Key Information
Ursodiol has interesting mechanisms of action, appears reasonably safe and well-tolerated, has anecdotal reports of benefit in 6/21 of patients who report taking it, and a form of it (Yoo’s solution) was associated with slightly slower ALS progression in one out of three outcome measures within a poorly designed study that did not account for large numbers of drop-outs. However, analyses of ursodiol data from the well-conducted randomized, double-blind ceftriaxone trial show that ursodiol 300 mg twice a day is no better than placebo at prolonging survival or slowing ALS progression. Based upon this review, ALSUntangled does not recommend off-label use of ursodiol as a treatment for ALS, at least at doses of 300 mg twice a day. Determining whether higher doses or different formulations are effective will require further well-designed studies.