J Korean Med Sci.  2012 Feb;27(2):200-206. 10.3346/jkms.2012.27.2.200.

Oral Solubilized Ursodeoxycholic Acid Therapy in Amyotrophic Lateral Sclerosis: A Randomized Cross-Over Trial

• Min JH
• Hong YH
• Sung JJ
• Kim SM
• Lee JB
• Lee KW

• KMID: 1120159
• DOI: http://doi.org/10.3346/jkms.2012.27.2.200

Abstract

To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) with oral solubilized formula in amyotrophic lateral sclerosis (ALS) patients, patients with probable or definite ALS were randomized to receive oral solubilized UDCA (3.5 g/140 mL/day) or placebo for 3 months after a run-in period of 1 month and switched to receive the other treatment for 3 months after a wash-out period of 1 month. The primary outcome was the rate of progression, assessed by the Appel ALS rating scale (AALSRS), and the secondary outcomes were the revised ALS functional rating scale (ALSFRS-R) and forced vital capacity (FVC). Fifty-three patients completed either the first or second period of study with only 16 of 63 enrolled patients given both treatments sequentially. The slope of AALSRS was 1.17 points/month lower while the patients were treated with UDCA than with placebo (95% CI for difference 0.08-2.26, P = 0.037), whereas the slopes of ALSFRS-R and FVC did not show significant differences between treatments. Gastrointestinal adverse events were more common with UDCA (P < 0.05). Oral solubilized UDCA seems to be tolerable in ALS patients, but we could not make firm conclusion regarding its efficacy, particularly due to the high attrition rate in this cross-over trial.

Keyword

Amyotrophic Lateral Sclerosis; Ursodeoxycholic Acid; Cross-Over Trial

MeSH Terms

Administration, Oral
Amyotrophic Lateral Sclerosis/*drug therapy
Cholagogues and Choleretics/pharmacology/therapeutic use
Cross-Over Studies
Double-Blind Method
Female
Humans
Male
Middle Aged
Placebo Effect
Severity of Illness Index
Ursodeoxycholic Acid/pharmacology/*therapeutic use
Vital Capacity/drug effects

Figure

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  Fig. 1 Trial profile. *all not meeting inclusion criteria; †one ineligible patient was randomized in error; ‡excluded from analysis due to a rapid rate of progression, i.e., the Appel ALS total score change > 8 points/month.

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  Fig. 2 Kaplan-Meier survival curves, using a change of 20 points on the Appel ALS total score as the end point. Time to 20 points progression was estimated by assuming a linearity of the change in the Appel ALS total score. In two patients whose slope was not above zero (zero in one, and -0.33 point/month in the other, both treated with oral solubilized UDCA), the time to 20 point progression was estimated to be 60 months, i.e., 1 point/3 month.

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