Trial on the Biological and Clinical Effects of Acetyl-L-carnitine in ALS
Status:
Not yet recruiting
Trial end date:
2026-09-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 2/Phase 3
Details
Lead Sponsor:
Mario Negri Institute for Pharmacological Research