Amyotrophic Lateral SclerosisPhase 2/3ALCALSNCT06126315
Trial on the Biological and Clinical Effects of Acetyl-L-carnitine in ALS
A Phase 2/3 study testing Acetyl-l-carnitine in people with Amyotrophic Lateral Sclerosis, run by Mario Negri Institute for Pharmacological Research at 19 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Acetyl-l-carnitine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 246 participants
- Where
- 19 sitesin 2 countries
- Study dates
- 26 Mar 2025to Sep 2027
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18+;
- ALS diagnosis according to the Gold Coast Criteria;
- Disease duration < 24 months from symptom onset, as indicated by limb weakness or bulbar symptoms, at the randomization/baseline visit*;
- Self-sufficiency [Satisfactory bulbar and spinal function (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.
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- Ability to understand and comply with the study requirements;
- Ability to give written informed consent personally or, as an alternative, via a legally authorized representative;
- Treatment with riluzole 50 mg twice/day for at least 4 weeks prior to randomization visit;
- Intact cognitive function, again determined by the Principal Investigator.
- The qualifying first symptoms of ALS are limited to manifestations of weakness in extremity, bulbar, or respiratory muscles. Cramps, fasciculations, or fatigue should not be taken in isolation as a first symptom of ALS.
Who cannot join
- Antecedent polio infection or other active infection;
- Motor neuron disease (MND) other than ALS;
- Involvement of other systems possibly determining a functional impairment (as measured by the endpoints) for the entire duration of the study;
- Other severe clinical conditions (e.g., cardiovascular disorders, neoplasms) with an impact on survival or functional disability in the next 12 months;
- Previous use of ALCAR for any reason;
- Poor compliance with previous treatments;
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- Other experimental treatments in the three months prior to the screening visit (if a subject is receiving another experimental drug, a 3-month wash-out period before participating in the present clinical trial will be required);
- Women who are lactating or able to become pregnant (e.g. who are not post-menopausal, surgically sterile, or using inadequate birth control) and men unable to practice contraception for the duration of the treatment and three months after its completion;
- Inability to understand and comply with the study requirements;
- Unwillingness or inability to take riluzole.
Trial locations and contacts
19 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
19 sites in 2 countries
Italy18 sites, 18 recruiting
- Recruiting
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Dipartimento di Neurologia
Bergamo, Italy, 24127
Marcella Vedovello, MD, +390352678906, mvedovello@asst-pg23.it
- Recruiting
Fondazione Serena ONLUS Centro Clinico NEMO Brescia
Brescia, Brescia, 25064
Massimiliano Filosto, MD, +39 0306729100, massimiliano.filosto@unibs.it
Chiara Colombi, chiara.colombi@centrocliniconemo.it
- Recruiting
Istituto Auxologico Italiano, IRCCS Dipartimento di Neurologia
Milan, Italy, 20149
Alberto Doretti, MD, +3902619112937, a.doretti@auxologico.it
- Recruiting
Fondazione Serena ONLUS centro clinico NEMO
Milan, Milano, 20162
Federica Cerri, MD, +39 02914 3371, federica.cerri@centrocliniconemo.it
Jasmine Refran, jasmine.refran@centrocliniconemo.it
- Recruiting
AOU di Modena Nuovo Ospedale Civile S. Agostino Estense di Modena - Ospedale di Baggiovara
Modena, Modena, 41126
Jessica Mandrioli, MD, +39 0593961640, jessica.mandrioli@unimore.it
Giulia Gianferrari, gianferrari.giulia@gmail.com
- Recruiting
Azienda Ospedaliera Universitaria Federico II Di Napoli
Naples, Italy, 80131
Raffaele Dubbioso, MD, +390817454587, Raffaele.dubbioso@unina.it
- Not yet recruiting
Azienda Ospedaliera Universitaria "Luigi Vanvitelli", Dipartimento di Scienze mediche e chirurgiche avanzate
Naples, Italy, 80138
Francesca Trojsi, MD, +390815665659, francesca.trojsi@unicampania.it
- Recruiting
Azienda Ospedaliero-Universitaria Maggiore della Carità
Novara, Italy, 28100
Fabiola De Marchi, MD, +39, fabiola.demarchi@uniupo.it
- Recruiting
Azienda Ospedale-Università di Padova, Unità di Neurologia Clinica
Padova, Italy, 35128
Gianni Sorarù, MD, +39049 8216394, centro.motoneurone@aopd.veneto.it
- Not yet recruiting
A.S.P. Palermo, Villa delle Ginestre Hospital
Palermo, Italy, 90135
Rossella Spataro, MD, +39 0916743111, rossella.spataro@asppalermo.org
- Recruiting
Fondazione Mondino Istituto Neurologico Nazionale a Carattere Scientifico IRCCS
Pavia, Pavia, 27100
Luca Diamanti, MD, +39 0382491929, luca.diamanti@mondino.it
- Recruiting
Fondazione Serena ONLUS-Centro Clinico NEMO Trento
Pergine Valsugana, Italy, 38057
Riccardo Zuccarino, MD, +390461515400, riccardo.zuccarino@centrocliniconemo.it
Raffaella Tanel, MD
- Not yet recruiting
Azienda Ospedaliera di Perugia
Perugia, Italy, 06156
Paola Brunori, MD, +39 075 5781, paola.brunori@ospedale.perugia.it
- Not yet recruiting
Azienda Ospedaliero Universitaria Pisana, Dipartimento di Medicina Clinica e Sperimentale
Pisa, Italy
Gabriele Siciliano, MD, +39050993604, g.siciliano@med.unipi.it
- Recruiting
Azienda Ospedaliero Universitaria Pisana
Pisa, Pisa, 56124
Paolo Bongioanni, MD, +39 050996964, bongioanni.paolo@gmail.com
- Not yet recruiting
San Camillo Forlanini Hospital, Center for Neuromuscolar and Neurological Rare Diseases, Unit of Neurology and Neurophysiopathology
Roma, Italy, 00152
Antonio Petrucci, MD, +39 0658704530, anpetrucci@scamilloforlanini.rm.it
- Recruiting
Azienda Ospedaliero-Universitaria Policlinico Umberto I - Università di Roma "La Sapienza"
Roma, Roma, 00161
Maurizio Inghilleri, MD, +39 0649914485 (24485), maurizio.inghilleri@uniroma1.it
Laura Libonati, MD, laura.libonati@uniroma1.it
- Recruiting
Fondazione Serena ONLUS - Centro Clinico NeMO Ancona
Torrette, Italy, 60126
Michela Coccia, MD, +39 0715965978, michela.coccia@centrocliniconemo.it
Australia1 site, 1 recruiting
- Recruiting
Concord Hospital
Sydney, Australia, 2139
Julie Ryder, +61 02 9767 8461, julie.ryder@health.nsw.gov.au
About this study
Official title: A Randomized, Phase II/III Trial on the Biological and Clinical Effects of Acetyl-L-carnitine in ALS
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.
Read more
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.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Acetyl-l-carnitine, Placebo
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetyl-l-carnitineDrug
Acetyl-l-carnitine
PlaceboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| alcar 1.5 g | Experimental | 2 pockets of ALCAR will be administered t.i.d for 48 weeks. Total daily dosage: 1.5 g Receives: Drug: Acetyl-l-carnitine |
| alcar 3 g | Experimental | 2 pockets of ALCAR will be administered t.i.d for 48 weeks. Total daily dosage: 3 g Receives: Drug: Acetyl-l-carnitine |
| placebo | Placebo comparator | 2 pockets of placebo will be administered t.i.d for 48 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
self-sufficient
The proportion of participants remaining self-sufficient after 48 weeks in each treatment arm
Measured: 48 weeks
Secondary outcomes (11)
Mean change of ALSFRS-R total score in each treatment arm
Mean change of ALSFRS-R total score in each treatment arm
Measured: from baseline to week 48
Mean change of FVC% in each treatment arm
Mean change of FVC% in each treatment arm
Measured: from baseline to week 48
Mean change in the five domains of ALSAQ-40 measuring different aspects of quality of life (physical mobility, ADL/independence, eating and drinking, emotional reactions, communication) in each treatment arm
Mean change in the five domains of ALSAQ-40 measuring different aspects of quality of life (physical mobility, ADL/independence, eating and drinking, emotional reactions, communication) in each treatment arm
Measured: from baseline to week 48
Mean change in ECAS total score in each treatment arm
Mean change in ECAS total score in each treatment arm
Measured: from baseline to week 48
Cumulative probability of remaining self-sufficient in each treatment arm
Cumulative probability of remaining self-sufficient in each treatment arm
Measured: from baseline to week 48
Cumulative probability of remaining free from a 6-point or greater decline in ALSFRS-R total score in each treatment arm
Cumulative probability of remaining free from a 6-point or greater decline in ALSFRS-R total score in each treatment arm
Measured: from baseline to week 48
Cumulative probability of remaining without gastrostomy in each treatment arm
Cumulative probability of remaining without gastrostomy in each treatment arm
Measured: from baseline to week 48
Cumulative probability of remaining without non-invasive ventilation (NIV) support (≥12 hours a day in a 24-hour period) in each treatment arm
Cumulative probability of remaining without non-invasive ventilation (NIV) support (≥12 hours a day in a 24-hour period) in each treatment arm
Measured: from baseline to week 48
Cumulative survival probability (of being alive and without tracheostomy) in each treatment arm
Cumulative survival probability (of being alive and without tracheostomy) in each treatment arm
Measured: from baseline to week 48
The mean change in the levels of PGC-1 alpha, 3-NT, acetyl-PPIA in the peripheral blood mononuclear cells (PBMCs) and of NFL, MMP-9, MCP-1, CK, MiR-206, Musclin/osteocrin, Uric acid, HNE in plasma in each treatment arm, during the entire treatment period
The mean change in the levels of PGC-1 alpha, 3-NT, acetyl-PPIA in the peripheral blood mononuclear cells (PBMCs) and of NFL, MMP-9, MCP-1, CK, MiR-206, Musclin/osteocrin, Uric acid, HNE in plasma in each treatment arm, during the entire treatment period
Measured: from baseline to week 48
Number of adverse events and serious adverse events in each treatment arm
Number of adverse events and serious adverse events in each treatment arm
Measured: from baseline to week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2023
- Study start26 Mar 2025
- Primary completionApr 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 246 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mario Negri Institute for Pharmacological Research
- Sponsor type
- University, hospital or other
- Collaborators
- University of Sydney, FightMND
- Responsible party
- Sponsor
- Investigators
- Elisabetta Pupillo, PharmD, Study chair, Istituto Di Ricerche Farmacologiche Mario Negri
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06126315
- Sponsor's protocol ID
- ALCALS
- Acronym
- ALCALS
- Status last verified
- Oct 2026
- First submitted
- 6 Nov 2023
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No