Efficacy and Tolerability of Tauroursodeoxycholic Acid in Amyotrophic Lateral Sclerosis

Summary

The preclinical rationale for tauroursodeoxycholic acid (TUDCA) use in treating patients with amyotrophic lateral sclerosis (ALS) stems from the demonstration of antioxidant, antiapoptotic and neuroprotective properties of TUDCA in the central nervous system (CNS), both in vitro and in vivo models.

This protocol is meant for assessing if the addition of TUDCA to the conventional therapy can improve the therapeutic outcome in patients affected by ALS.

Safety will be assessed for all subjects, for the entire duration of the study. 30 patients affected by ALS with site of onset in the limbs will be recruited.

All enrolled subjects will continue receiving riluzole at the same regimen as before entering the trial. Based on an appropriate random code, subjects will be divided into two groups of equal size treated, after a lead-in period of 3 months, by oral route with TUDCA at the dose 2 g daily for 1 year or with identical placebo by oral route at the same dosing schedule, under double-blind conditions.

Every concomitant and/or supportive therapy will be admitted.

Evaluation criteria:

Efficacy. The proportion of responder patients in the two treatment groups was the primary outcome measure of the study. Responder patients were defined as those subjects showing an improvement of at least 15% in the ALSFRS-R (2) slope during the treatment period as compared to the lead-in period. This threshold was chosen based according to the consensus conference on designing and implementing clinical trials in ALS (3).

Other parameters will include ALSFRS-R at study end, FVC%, the SF-36 quality of life rating scale, time to tracheotomy from starting of study medication dosing (if appropriate), survival Time from starting of study medication dosing (if appropriate), Medical Research Council scores for right and left muscle groups.

Safety. Incidence, severity and type of adverse events; changes in clinical laboratory findings.

Conditions

• Amyotrophic Lateral Sclerosis

Interventions

DRUG

tauroursodeoxycholic acid (TUDCA)

Oral route at the dose of 1 g b.i.d. (2 g daily) for 1 year

DRUG

Placebo

identical placebo by oral route at the same dosing schedule

Sponsors & Collaborators

• University of Palermo

  collaborator OTHER

• Federico II University

  collaborator OTHER

• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

  lead OTHER

Principal Investigators

• Alberto Albanese, MD · Fondazione IRCCS Istituto neurologico Carlo Besta

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-06-30

Primary Completion

2011-07-31

Completion

2012-04-30

Countries

• Italy

Study Locations