Efficacy and Tolerability of Tauroursodeoxycholic Acid in Amyotrophic Lateral Sclerosis
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Intervention: tauroursodeoxycholic acid (TUDCA); Placebo
Intervention description: Oral route at the dose of 1 g b.i.d. (2 g daily) for 1 year; identical placebo by oral route at the same dosing schedule
Intervention MeSH terms: Ursodoxicoltaurine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: ALS; Therapy; Tauroursodeoxycholic acid; TUDCA; antioxidant; antiapoptotic drug; neuroprotective drug

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Caucasian male or female out-patients;

          -  aged 18 to 75 years inclusive;

          -  diagnosis of "probable" or "definite" amyotrophic lateral sclerosis according to the
             El Escorial revised criteria (1);

          -  first symptoms of ALS by no more than 1.5 years;

          -  in treatment with steady regimen of riluzole for a minimum of 3 months before study
             entry, and desiring its continuation;

          -  FVC ≥ 75% of predicted;

          -  no conditions known to be contraindications to the use of TUDCA;

          -  written informed consent.

        Exclusion Criteria:

          -  subjects who underwent tracheostomy;

          -  subjects who underwent resection of gall bladder;

          -  subjects with signs of conduction blocks of motor nerves, sensory nerves or both on
             nerve conduction study;

          -  subjects with clinical signs of dementia;

          -  subjects with active peptic ulcer;

          -  subjects with active malignancy;

          -  subjects with bulbar onset;

          -  female subjects who are pregnant or lactating

          -  subjects who have received an experimental drug or have participated in a clinical
             trial within 3 months prior to screening

          -  employees of the investigator or study centre with direct involvement in the proposed
             study or other studies under the direction of that investigator or study centre.