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Forsøg på de biologiske og kliniske virkninger af acetyl-L-carnitin i ALS (ALCALS)

Et randomiseret, fase II/III-forsøg om de biologiske og kliniske virkninger af acetyl-L-carnitin i 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.

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.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

246

Fase

  • Fase 2
  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: alcar 1.5 g

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

Acetyl-l-carnitine

Eksperimentel: alcar 3 g

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

Acetyl-l-carnitine

Placebo komparator: placebo

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

placebo

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
self-sufficient
Tidsramme: 48 weeks

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

48 weeks

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Mean change of ALSFRS-R total score in each treatment arm
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: from baseline to week 48

Number of adverse events and serious adverse events in each treatment arm

from baseline to week 48

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Samarbejdspartnere

Efterforskere

  • Studiestol: Elisabetta Pupillo, PharmD, Istituto Di Ricerche Farmacologiche Mario Negri

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

26. marts 2025

Primær færdiggørelse (Anslået)

1. april 2027

Studieafslutning (Anslået)

1. september 2027

Datoer for studieregistrering

Først indsendt

6. november 2023

Først indsendt, der opfyldte QC-kriterier

6. november 2023

Først opslået (Faktiske)

13. november 2023

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

6. oktober 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

5. oktober 2026

Sidst verificeret

1. oktober 2026

Mere information

Begreber relateret til denne undersøgelse

Andre undersøgelses-id-numre

  • ALCALS

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ingen

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .