Efficacy and Tolerability of Tauroursodeoxycholic Acid in Amyotrophic Lateral Sclerosis (TUDCA-ALS)
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.
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.
|Amyotrophic Lateral Sclerosis||Drug: tauroursodeoxycholic acid (TUDCA) Drug: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomized, Double-blind Multicenter Pilot Study vs. Placebo for the Evaluation of Efficacy and Tolerability of Tauroursodeoxycholic Acid Administered by Oral Route as Add on Treatment in Patients Affected by Amyotrophic Lateral Sclerosis|
- The Proportion of Responder Patients in the Two Treatment Groups According the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS)-R Slope. [ Time Frame: 1 year ]Responder patients were defined as those subjects showing an improvement of at least 15% in the ALSFRS-R slope during the treatment period as compared to the lead-in period.
- Forced Vital Capacity (FVC) % [ Time Frame: 1 year ]
- SF-36 Quality of Life Rating Scale [ Time Frame: 1 year ]
- Time to Tracheostomy From Starting of Study Medication Dosing (if Appropriate) [ Time Frame: 1 year ]
- Survival Time From Starting of Study Medication Dosing (if Appropriate) [ Time Frame: 1 year ]
- ALSFRS-R at Study End [ Time Frame: 1 year ]
- Incidence and Severity of Adverse Events, and Their Relationship to Treatment [ Time Frame: 1 year ]laboratory tests, patients' reports and the investigator's judgments
- Medical Research Council Scores for Right and Left Muscle Groups [ Time Frame: 1 year ]
|Study Start Date:||June 2008|
|Study Completion Date:||April 2012|
|Primary Completion Date:||July 2011 (Final data collection date for primary outcome measure)|
tauroursodeoxycholic acid di-hydrate
Drug: tauroursodeoxycholic acid (TUDCA)
Oral route at the dose of 1 g b.i.d. (2 g daily) for 1 year
Placebo Comparator: placebo
identical placebo by oral route at the same dosing schedule
Other Name: Oral route at the dose of 1 g b.i.d. (2 g daily) for 1 year
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00877604
|Fondazione IRCCS Istituto neurologico Carlo Besta|
|Milan, Italy, 20133|
|Principal Investigator:||Alberto Albanese, MD||Fondazione IRCCS Istituto neurologico Carlo Besta|