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Ensaio sobre os efeitos biológicos e clínicos da acetil-L-carnitina na ELA (ALCALS)

5 de outubro de 2026 atualizado por: Mario Negri Institute for Pharmacological Research

Um ensaio randomizado de fase II/III sobre os efeitos biológicos e clínicos da acetil-L-carnitina na ELA

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.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Estimado)

246

Estágio

  • Fase 2
  • Fase 3

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Locais de estudo

  • Austrália
    • Australia
      • Sydney, Australia, Austrália, 2139
  • Itália
    • Brescia
    • Italy
      • Bergamo, Italy, Itália, 24127
        • Recrutamento
        • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Dipartimento di Neurologia
        • Contato:
      • Milan, Italy, Itália, 20149
        • Recrutamento
        • Istituto Auxologico Italiano, IRCCS Dipartimento di Neurologia
        • Contato:
      • Naples, Italy, Itália, 80131
        • Recrutamento
        • Azienda Ospedaliera Universitaria Federico II Di Napoli
        • Contato:
      • Naples, Italy, Itália, 80138
        • Ainda não está recrutando
        • Azienda Ospedaliera Universitaria "Luigi Vanvitelli", Dipartimento di Scienze mediche e chirurgiche avanzate
        • Contato:
      • Novara, Italy, Itália, 28100
        • Recrutamento
        • Azienda Ospedaliero-Universitaria Maggiore della Carità
        • Contato:
      • Padova, Italy, Itália, 35128
        • Recrutamento
        • Azienda Ospedale-Università di Padova, Unità di Neurologia Clinica
        • Contato:
      • Palermo, Italy, Itália, 90135
        • Ainda não está recrutando
        • A.S.P. Palermo, Villa delle Ginestre Hospital
        • Contato:
      • Pergine Valsugana, Italy, Itália, 38057
        • Recrutamento
        • Fondazione Serena ONLUS-Centro Clinico NEMO Trento
        • Contato:
        • Subinvestigador:
          • Raffaella Tanel, MD
      • Perugia, Italy, Itália, 06156
      • Pisa, Italy, Itália
        • Ainda não está recrutando
        • Azienda Ospedaliero Universitaria Pisana, Dipartimento di Medicina Clinica e Sperimentale
        • Contato:
      • Roma, Italy, Itália, 00152
        • Ainda não está recrutando
        • San Camillo Forlanini Hospital, Center for Neuromuscolar and Neurological Rare Diseases, Unit of Neurology and Neurophysiopathology
        • Contato:
      • Torrette, Italy, Itália, 60126
        • Recrutamento
        • Fondazione Serena ONLUS - Centro Clinico NeMO Ancona
        • Contato:
    • Milano
    • Modena
      • Modena, Modena, Itália, 41126
    • Pavia
      • Pavia, Pavia, Itália, 27100
        • Recrutamento
        • Fondazione Mondino Istituto Neurologico Nazionale a Carattere Scientifico IRCCS
        • Contato:
    • Pisa
      • Pisa, Pisa, Itália, 56124
        • Recrutamento
        • Azienda Ospedaliero Universitaria Pisana
        • Contato:
    • Roma
      • Roma, Roma, Itália, 00161
        • Recrutamento
        • Azienda Ospedaliero-Universitaria Policlinico Umberto I - Università di Roma "La Sapienza"
        • Contato:
        • Contato:

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  1. Age 18+;

  2. ALS diagnosis according to the Gold Coast Criteria;

  3. Disease duration < 24 months from symptom onset, as indicated by limb weakness or bulbar symptoms, at the randomization/baseline visit*;

  4. Self-sufficiency [Satisfactory bulbar and spinal function (score 3+ on the ALSFRS-R for swallowing, cutting food and handling utensils, and walking)];

  5. Satisfactory respiratory function (FVC ≥80% of predicted);

  6. 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.

  7. Ability to understand and comply with the study requirements;

  8. Ability to give written informed consent personally or, as an alternative, via a legally authorized representative;

  9. Treatment with riluzole 50 mg twice/day for at least 4 weeks prior to randomization visit;

  10. 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.

Exclusion Criteria:

  1. Antecedent polio infection or other active infection;
  2. Motor neuron disease (MND) other than ALS;
  3. Involvement of other systems possibly determining a functional impairment (as measured by the endpoints) for the entire duration of the study;
  4. Other severe clinical conditions (e.g., cardiovascular disorders, neoplasms) with an impact on survival or functional disability in the next 12 months;
  5. Previous use of ALCAR for any reason;
  6. Poor compliance with previous treatments;
  7. 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);
  8. 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;
  9. Inability to understand and comply with the study requirements;
  10. Unwillingness or inability to take riluzole.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Quadruplicar

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: alcar 1.5 g

2 pockets of ALCAR will be administered t.i.d for 48 weeks. Total daily dosage: 1.5 g
Medicamento: Acetyl-l-carnitine

Acetyl-l-carnitine
Experimental: alcar 3 g

2 pockets of ALCAR will be administered t.i.d for 48 weeks. Total daily dosage: 3 g
Medicamento: Acetyl-l-carnitine

Acetyl-l-carnitine
Comparador de Placebo: placebo

2 pockets of placebo will be administered t.i.d for 48 weeks.
Medicamento: Placebo

placebo

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
self-sufficient
Prazo: 48 weeks

The proportion of participants remaining self-sufficient after 48 weeks in each treatment arm
48 weeks

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Mean change of ALSFRS-R total score in each treatment arm
Prazo: from baseline to week 48

Mean change of ALSFRS-R total score in each treatment arm
from baseline to week 48
Mean change of FVC% in each treatment arm
Prazo: from baseline to week 48

Mean change of FVC% in each treatment arm
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
Prazo: 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
from baseline to week 48
Mean change in ECAS total score in each treatment arm
Prazo: from baseline to week 48

Mean change in ECAS total score in each treatment arm
from baseline to week 48
Cumulative probability of remaining self-sufficient in each treatment arm
Prazo: from baseline to week 48

Cumulative probability of remaining self-sufficient in each treatment arm
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
Prazo: 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
from baseline to week 48
Cumulative probability of remaining without gastrostomy in each treatment arm
Prazo: from baseline to week 48

Cumulative probability of remaining without gastrostomy in each treatment arm
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
Prazo: 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
from baseline to week 48
Cumulative survival probability (of being alive and without tracheostomy) in each treatment arm
Prazo: from baseline to week 48

Cumulative survival probability (of being alive and without tracheostomy) in each treatment arm
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
Prazo: 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
from baseline to week 48
Number of adverse events and serious adverse events in each treatment arm
Prazo: from baseline to week 48

Number of adverse events and serious adverse events in each treatment arm
from baseline to week 48

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Mario Negri Institute for Pharmacological Research

Colaboradores

University of Sydney
FightMND

Investigadores

  • Cadeira de estudo: Elisabetta Pupillo, PharmD, Istituto Di Ricerche Farmacologiche Mario Negri

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

26 de março de 2025

Conclusão Primária (Estimado)

1 de abril de 2027

Conclusão do estudo (Estimado)

1 de setembro de 2027

Datas de inscrição no estudo

Enviado pela primeira vez

6 de novembro de 2023

Enviado pela primeira vez que atendeu aos critérios de CQ

6 de novembro de 2023

Primeira postagem (Real)

13 de novembro de 2023

Atualizações de registro de estudo

Última Atualização Postada (Real)

6 de outubro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

5 de outubro de 2026

Última verificação

1 de outubro de 2026

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • ALCALS

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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