Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS (TUDCA-ALS)
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|ClinicalTrials.gov Identifier: NCT03800524|
Recruitment Status : Not yet recruiting
First Posted : January 11, 2019
Last Update Posted : January 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|Amyotrophic Lateral Sclerosis (ALS)||Drug: Tauroursodeoxycholic acid (TUDCA) Drug: Placebo||Phase 3|
Enrolled patients will be randomized to one of two treatment arms: TUDCA or identical placebo by oral route. The randomization will be performed in a ratio one to one for the two arms.
TUDCA will be administered orally at the dose of 1 g twice daily (2 g daily) for 18 months. Patients will be taking also riluzole at the dose of 50 mg twice daily (100 mg daily).
Patient randomization will take place after a screening (lead-in) period of 12 weeks (3 months) with 3 assessments at 6-week intervals. Clinical assessments during the trial phase will be performed every three months (see dia-gram). This will allow measuring the progression rate before and after starting treatment (either active or placebo).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||440 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Safety and Efficacy of Tauroursodeoxycholic (TUDCA) as add-on Treatment in Patients Affected by Amyotrophic Lateral Sclerosis (ALS)|
|Estimated Study Start Date :||January 2019|
|Estimated Primary Completion Date :||December 1, 2019|
|Estimated Study Completion Date :||June 1, 2022|
Experimental: Tauroursodeoxycholic acid (TUDCA)
Drug: Tauroursodeoxycholic acid (TUDCA)
Other Name: a hydrophilic bile acid
Placebo Comparator: Reference therapy
- Number of responder patients [ Time Frame: 18 months ]Identification of the responder patients defined as those showing an improvement of at least 20% in the ALSFRS-R slope
- Survival time [ Time Frame: 18 months ]Survival time measured by death or respiratory insufficiency
- ALS disease functional rating scale - revised version (ALSFRS-R) [ Time Frame: 18 months ]Difference in change from baseline in ALSFRS-R. Each task of the scale is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score ranging from 0 = worst to 48 = best.
- ALS Assessment Questionnaire‐40 (ALSAQ-40) [ Time Frame: 18 months ]Difference in change from baseline in ALSAQ-40. The instrument contains 40 statements that measure five dimensions of health state: Physical Mobility (10 statements), Activities of Daily Living and Independence (10 statements), Eating and Drinking (5 statements), Communication (5 statements), Emotional Functioning (10 statements). The pa-tient must indicate how often (Never, Rarely, Sometimes, Often, or Always) the statement have been true. Dimension scores are coded on a likert scale, ranging from 0 (best health as assessed by the scale) to 100 (worse health as assessed by the measure).
- Forced Vital Capacity [ Time Frame: 18 months ]Difference in change from baseline in Forced Vital Capacity
- EuroQol 5‐Dimension-5 Levels (EQ-5D-5L) scale [ Time Frame: 18 months ]Difference in change from baseline in EQ-5D-5L scale. The EQ-5D-5L descriptive system comprises 5 dimensions (mobility, self-care, usual activi-ties, pain/discomfort and anxiety/depression). Each dimension has 5 levels: 1.no problems, 2.slight problems, 3.moderate problems, 4.severe problems, 5.extreme problems. The patient is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions. This decision results in a 1-digit number express-ing the level selected for that dimension. The digits for 5 dimensions can be combined in a 5-digit number describing the patient health state. Numbers 1-5 have no arithmetic properties and should not be used as a cardinal score.
- Medical Research Council (MRC) scale [ Time Frame: 18 months ]Difference in change from baseline in muscle force assessed by the MRC scale. The scale rates muscle strength of 6 muscles (3 at the upper and 3 at the lower limbs), bilaterally. Each muscle is graded from 0 = no movement, to 5 = normal strength, giving a total sum-score that ranges from 0 (total paralysis) to 60 (normal strength).
- Neurofilaments levels [ Time Frame: 18 months ]Effect of TUDCA on Neurofilament levels in comparison to placebo
- MMP-9 levels [ Time Frame: 18 months ]Effect of TUDCA on MMP-9 expression in comparison to placebo