Safety and efficacy of tauroursodeoxycholic acid (TUDCA) as add-on treatment in patients affected by amyotrophic lateral sclerosis (ALS)

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

1. laboratory-supported, probable, or definite ALS diagnosis, as defined by El
Escorial Revised ALS diagnostic criteria
2. Disease duration <= 18 months
3. No swallowing difficulty (4 at ALSFRS-R swallowing subscore)
4. Able to perform reproducible pulmonary function tests
5. Forced vital capacity >=70% of normal
6. Stable on riluzole treatment for 3 months in the lead-in period
7. Signed informed consent

All patients who entered and completed the TUDCA-ALS clinical trial can be
included in the open-label TUDCA-ALS Extension.

1. Completion of the visit M18 (Month 18) of the TUDCA-ALS clinical trial.
2. Signed informed consent for participation in the TUDCA-ALS Extension
sub-study.

Exclusion Criteria

1. Treatment with edaravone or other unaccepted concomitant therapy (substances
inhibiting the intestinal absorption of bili-ary acids, antacids containing
aluminium hydroxide and/or smectites, estrogens and drugs acting by lowering
plasmatic cholesterol; drugs increasing biliary clearance of cholesterol,
hepatolesive drugs)
2. Other causes of neuromuscular weakness
3. Presence of other neurodegenerative diseases
4. Significant cognitive impairment, clinical dementia or psychiat-ric illness
5. Severe cardiac or pulmonary disease
6. Other diseases precluding functional assessments
7. Other life-threatening diseases
8. At the time of screening, any use of non-invasive ventilation for any
portion of the day, or mechanical ventilation via tracheost-omy, or on any form
of oxygen supplementation
9. Gastrointestinal disorder that is likely to impair absorption of study drug
from the gastrointestinal tract
10. Has taken any investigational study drug within 30 days or five half-lives
of the prior agent, whichever is longer, prior to dosing
11. Any clinically significant laboratory abnormality
12. Other concurrent investigational medications
13. Active peptic ulcer
14. Previous surgery or infections of small intestine
15. Patients unable to easily swallow the treatment pills at time of enrolment
16. Occurrence of frequent biliary colic, biliary infections, severe pancreatic
abnormalities
17. Subjects who weigh 88 lbs (40 kg) or less at screening
18. Sieric Aspartate aminotransferase or alanine aminotransferase
concentrations more than 3 times the upper limit of normal
19. Creatinine clearance 50 ml/min or less
20. Any clinically significant neurological, haematological, autoim-mune,
endocrine, cardiovascular, neo-plastic, renal, gastroin-testinal, or other
disorder that, in the Investigator's opinion, could interfere with the
subject's participation in the study, place the subject at increased risk, or
confound interpretation of study results
21. Consideration by the investigator, for any reason, that the sub-ject is an
unsuitable candidate to receive TUDCA or that the subject is unable or unlikely
to comply with the dosing schedule or study evaluations
22. The patient is sexually active and is not willing to use highly ef-fective
contraception during the study and up to 90 days after the day of last dose

1. Treatment with edaravone or other unaccepted concomitant therapy (as per
section 8 of the main TUDCA-ALS clinical trial protocol)
2. Consideration by the investigator, for any reason, that the subject is an
unsuitable candidate to re-ceive TUDCA or that the subject is unable or
unlikely to comply with the dosing schedule or study evaluations
3. The patient of reproductive potential is sexually active and is not willing
to use highly effective con-traception during the study and up to 90 days after
the day of last dose (see Contraceptive Guidance in Appendix A)
4. The patient is pregnant or breast feeding

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of the study is:<br /><br>* To assess the efficacy of TUDCA in slowing disease progression in patients<br /><br>with ALS during the treatment period compared to the lead-in phase), as<br /><br>measured by ALSFRS-R.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary objectives of this study are:<br /><br>* To assess the efficacy of TUDCA in slowing disease progression and functional<br /><br>impairment in patients with ALS, as measured by the survival time, the ALSAQ-40<br /><br>questionnaire, FVC, the EQ-5D, and muscle force<br /><br>* To assess the long term safety and tolerability of TUDCA for up to 18 months<br /><br>in patients with ALS</p><br>