Trial on the Biological and Clinical Effects of Acetyl-L-carnitine in ALS - Trial NCT06126315

Timeline & Enrollment

Primary Outcome

self-sufficient

Summary

Phase II/III multicenter, randomized, double-blind, placebo-controlled trial on
 acetyl-L-carnitine (ALCAR) in subjects living with amyotrophic lateral sclerosis (ALS).
 Primary study aim: The clinical objective consists of assessing the efficacy of ALCAR (two
 different dosages will be tested: 1.5g/day and 3g/day) on the progression of functional
 disability (loss of self-sufficiency), as measured by the ALSFRS-R scale. Secondary study
 aims: 1. The effect of ALCAR treatment on different clinical aspects: functional decline as
 measured by ALSFRS-R total score; the decline of forced vital capacity (FVC); quality of life
 as measured by ALSAQ-40 scale; cognitive function as measured by Edinburgh Cognitive and
 Behavioural ALS Screen (ECAS) scale; survival (being alive and without tracheostomy). 2. To
 measure the effects of ALCAR treatment on disease biomarkers potentially involved in the
 drug's mechanisms of action. These include PGC-1 alpha, 3-nitrotyrosine (3-NT), acetyl
 cyclophilin A (acetyl-PPIA), neurofilament light chain (NFL), creatine kinase (CK),
 Musclin/osteocrin, MyomiRNA (MiR-206), Uric acid, Matrix metalloproteinase-9 (MMP-9),
 Monocyte Chemoattractant Protein-1 (MCP-1), 4-Hydroxynonenal (HNE). 3. The tolerability and
 safety of ALCAR treatment by identifying unexpected adverse events.
 
 Study population: 246 subjects will be enrolled on one Australian and ten Italian ALS sites.
 
 Inclusion criteria: subjects aged 18+ years with a diagnosis of ALS according to Gold Coast
 Criteria; disease duration 24 months; satisfactory bulbar and spinal function
 (self-sufficiency evaluated by a score 3+ on the ALSFRS-R for swallowing, cutting food and
 handling utensils, and walking); satisfactory respiratory function (FVC ≥80% of predicted);
 documented progression of symptoms as measured by the ALSFRS-R scale. Disease progression
 rate (DFS) must be= 0.33. DFS =(48- ALSFRS-R at screening)/months from onset to screening,
 treatment with Riluzole in the last four weeks. Exclusion criteria: antecedent polio
 infection; other motor neuron disease; involvement of other systems possibly determining a
 functional impairment; other severe clinical conditions; unwillingness or inability to take
 riluzole; previous use of ALCAR for any reason; inability to understand and comply with the
 study requirements, and to give written informed consent personally or via their legally
 authorized representative.
 
 All eligible participants will be randomized to receive ALCAR (1,5 or 3 g/day) or placebo in
 addition to riluzole 50 mg b.i.d. Permuted block (with a block size of 6), 1:1:1 centralized
 randomization scheme will be used. The overall treatment duration will be 48 weeks. After
 enrolment, each participant will be followed up until death. Eligible subjects will be seen
 after 4, 12, 24, 36 and 48 weeks. At each visit, a general assessment will be made, including
 vital signs, body mass index (BMI), neurological examination (including quantitative and
 qualitative evaluation of the motor system), comorbidity, concomitant treatments and adverse
 events. Blood samples will be collected at baseline -Day 1 (randomization)-, 4, 12, 24, 36
 and 48 weeks to test biomarkers. Functional disability will be assessed at each visit using
 the ALS-FRS-R scale. The respiratory function will be assessed using a spirometer to measure
 FVC before starting treatment (baseline visit) and at 4, 12, 24, 36 and 48 weeks. Cognitive
 function will be evaluated at baseline, weeks 24 and 48, using ECAS scale. Health-related
 quality of life, measured by the ALSAQ-40, will be tested at baseline, 24 and 48 weeks.
 Compliance will be tested by the local investigators, counting unused packages at each
 follow-up visit. Pre-planned statistical analyses will be done on Intention-to-treat and
 Per-protocol (PP) populations. The statistical plan will include descriptive statistics and a
 comparison of the proportions of self-sufficient participants at week 48 using the chi-square
 or Fisher's exact test for the primary endpoint. Secondary endpoints measured by numerical
 scores obtained from clinical scales will be analyzed using repeated measures mixed models,
 while biomarkers using repeated measures ANOVA. Time-to-event endpoints, such as survival and
 the probability of remaining self-sufficient over 48 weeks, will be analyzed with
 Kaplan-Meier curves. The number of adverse events and serious adverse events after 48 weeks
 will be compared between treatment arms.

ICD-10 Classifications