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Ensayo sobre los efectos biológicos y clínicos de la acetil-L-carnitina en la ELA (ALCALS)

5 de octubre de 2026 actualizado por: Mario Negri Institute for Pharmacological Research

Un ensayo aleatorizado de fase II/III sobre los efectos biológicos y clínicos de la acetil-L-carnitina en la 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.

Descripción general del estudio

Estado

Reclutamiento

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Estimado)

246

Fase

  • Fase 2
  • Fase 3

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

Ubicaciones de estudio

  • Australia
    • Australia
      • Sydney, Australia, Australia, 2139
  • Italia
    • Brescia
    • Italy
      • Bergamo, Italy, Italia, 24127
        • Reclutamiento
        • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Dipartimento di Neurologia
        • Contacto:
      • Milan, Italy, Italia, 20149
        • Reclutamiento
        • Istituto Auxologico Italiano, IRCCS Dipartimento di Neurologia
        • Contacto:
      • Naples, Italy, Italia, 80131
        • Reclutamiento
        • Azienda Ospedaliera Universitaria Federico II Di Napoli
        • Contacto:
      • Naples, Italy, Italia, 80138
        • Aún no reclutando
        • Azienda Ospedaliera Universitaria "Luigi Vanvitelli", Dipartimento di Scienze mediche e chirurgiche avanzate
        • Contacto:
      • Novara, Italy, Italia, 28100
        • Reclutamiento
        • Azienda Ospedaliero-Universitaria Maggiore della Carità
        • Contacto:
      • Padova, Italy, Italia, 35128
        • Reclutamiento
        • Azienda Ospedale-Università di Padova, Unità di Neurologia Clinica
        • Contacto:
      • Palermo, Italy, Italia, 90135
        • Aún no reclutando
        • A.S.P. Palermo, Villa delle Ginestre Hospital
        • Contacto:
      • Pergine Valsugana, Italy, Italia, 38057
        • Reclutamiento
        • Fondazione Serena ONLUS-Centro Clinico NEMO Trento
        • Contacto:
        • Sub-Investigador:
          • Raffaella Tanel, MD
      • Perugia, Italy, Italia, 06156
        • Aún no reclutando
        • Azienda Ospedaliera di Perugia
        • Contacto:
      • Pisa, Italy, Italia
        • Aún no reclutando
        • Azienda Ospedaliero Universitaria Pisana, Dipartimento di Medicina Clinica e Sperimentale
        • Contacto:
      • Roma, Italy, Italia, 00152
        • Aún no reclutando
        • San Camillo Forlanini Hospital, Center for Neuromuscolar and Neurological Rare Diseases, Unit of Neurology and Neurophysiopathology
        • Contacto:
      • Torrette, Italy, Italia, 60126
        • Reclutamiento
        • Fondazione Serena ONLUS - Centro Clinico NeMO Ancona
        • Contacto:
    • Milano
    • Modena
      • Modena, Modena, Italia, 41126
        • Reclutamiento
        • AOU di Modena Nuovo Ospedale Civile S. Agostino Estense di Modena - Ospedale di Baggiovara
        • Contacto:
        • Contacto:
    • Pavia
      • Pavia, Pavia, Italia, 27100
        • Reclutamiento
        • Fondazione Mondino Istituto Neurologico Nazionale a Carattere Scientifico IRCCS
        • Contacto:
    • Pisa
      • Pisa, Pisa, Italia, 56124
        • Reclutamiento
        • Azienda Ospedaliero Universitaria Pisana
        • Contacto:
    • Roma
      • Roma, Roma, Italia, 00161
        • Reclutamiento
        • Azienda Ospedaliero-Universitaria Policlinico Umberto I - Università di Roma "La Sapienza"
        • Contacto:
        • Contacto:

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Cuadruplicar

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: alcar 1.5 g

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

Acetyl-l-carnitine
Comparador de placebos: placebo

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

placebo

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
self-sufficient
Periodo de tiempo: 48 weeks

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

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Mean change of ALSFRS-R total score in each treatment arm
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Mario Negri Institute for Pharmacological Research

Colaboradores

University of Sydney
FightMND

Investigadores

  • Silla de estudio: Elisabetta Pupillo, PharmD, Istituto Di Ricerche Farmacologiche Mario Negri

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

26 de marzo de 2025

Finalización primaria (Estimado)

1 de abril de 2027

Finalización del estudio (Estimado)

1 de septiembre de 2027

Fechas de registro del estudio

Enviado por primera vez

6 de noviembre de 2023

Primero enviado que cumplió con los criterios de control de calidad

6 de noviembre de 2023

Publicado por primera vez (Actual)

13 de noviembre de 2023

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

6 de octubre de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

5 de octubre de 2026

Última verificación

1 de octubre de 2026

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • ALCALS

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

NO

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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