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ALSにおけるアセチル-L-カルニチンの生物学的および臨床的効果に関する試験 (ALCALS)

2026年10月5日 更新者：Mario Negri Institute for Pharmacological Research

ALSにおけるアセチル-L-カルニチンの生物学的および臨床的効果に関する無作為化第II/III相試験

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.

調査の概要

状態

募集

条件

介入・治療

研究の種類

介入

入学 (推定)

246

段階

  • フェーズ2
  • フェーズ 3

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究場所

  • イタリア
    • Brescia
    • Italy
      • Bergamo、Italy、イタリア、24127
        • 募集
        • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Dipartimento di Neurologia
        • コンタクト：
      • Milan、Italy、イタリア、20149
        • 募集
        • Istituto Auxologico Italiano, IRCCS Dipartimento di Neurologia
        • コンタクト：
      • Naples、Italy、イタリア、80131
        • 募集
        • Azienda Ospedaliera Universitaria Federico II Di Napoli
        • コンタクト：
      • Naples、Italy、イタリア、80138
        • まだ募集していません
        • Azienda Ospedaliera Universitaria "Luigi Vanvitelli", Dipartimento di Scienze mediche e chirurgiche avanzate
        • コンタクト：
      • Novara、Italy、イタリア、28100
        • 募集
        • Azienda Ospedaliero-Universitaria Maggiore della Carità
        • コンタクト：
      • Padova、Italy、イタリア、35128
        • 募集
        • Azienda Ospedale-Università di Padova, Unità di Neurologia Clinica
        • コンタクト：
      • Palermo、Italy、イタリア、90135
        • まだ募集していません
        • A.S.P. Palermo, Villa delle Ginestre Hospital
        • コンタクト：
      • Pergine Valsugana、Italy、イタリア、38057
        • 募集
        • Fondazione Serena ONLUS-Centro Clinico NEMO Trento
        • コンタクト：
        • 副調査官：
          • Raffaella Tanel, MD
      • Perugia、Italy、イタリア、06156
        • まだ募集していません
        • Azienda Ospedaliera di Perugia
        • コンタクト：
      • Pisa、Italy、イタリア
        • まだ募集していません
        • Azienda Ospedaliero Universitaria Pisana, Dipartimento di Medicina Clinica e Sperimentale
        • コンタクト：
      • Roma、Italy、イタリア、00152
        • まだ募集していません
        • San Camillo Forlanini Hospital, Center for Neuromuscolar and Neurological Rare Diseases, Unit of Neurology and Neurophysiopathology
        • コンタクト：
      • Torrette、Italy、イタリア、60126
        • 募集
        • Fondazione Serena ONLUS - Centro Clinico NeMO Ancona
        • コンタクト：
    • Milano
    • Modena
      • Modena、Modena、イタリア、41126
        • 募集
        • AOU di Modena Nuovo Ospedale Civile S. Agostino Estense di Modena - Ospedale di Baggiovara
        • コンタクト：
        • コンタクト：
    • Pavia
      • Pavia、Pavia、イタリア、27100
        • 募集
        • Fondazione Mondino Istituto Neurologico Nazionale a Carattere Scientifico IRCCS
        • コンタクト：
    • Pisa
      • Pisa、Pisa、イタリア、56124
        • 募集
        • Azienda Ospedaliero Universitaria Pisana
        • コンタクト：
    • Roma
      • Roma、Roma、イタリア、00161
        • 募集
        • Azienda Ospedaliero-Universitaria Policlinico Umberto I - Università di Roma "La Sapienza"
        • コンタクト：
        • コンタクト：
  • オーストラリア
    • Australia
      • Sydney、Australia、オーストラリア、2139

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：4倍

武器と介入

参加者グループ / アーム
介入・治療
実験的：alcar 1.5 g

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

Acetyl-l-carnitine
実験的：alcar 3 g

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

Acetyl-l-carnitine
プラセボコンパレーター：placebo

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

placebo

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
self-sufficient
時間枠：48 weeks

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

二次結果の測定

結果測定
メジャーの説明
時間枠
Mean change of ALSFRS-R total score in each treatment arm
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：from baseline to week 48

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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Mario Negri Institute for Pharmacological Research

協力者

University of Sydney
FightMND

捜査官

  • スタディチェア：Elisabetta Pupillo, PharmD、Istituto Di Ricerche Farmacologiche Mario Negri

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2025年3月26日

一次修了 (推定)

2027年4月1日

研究の完了 (推定)

2027年9月1日

試験登録日

最初に提出

2023年11月6日

QC基準を満たした最初の提出物

2023年11月6日

最初の投稿 (実際)

2023年11月13日

学習記録の更新

投稿された最後の更新 (実際)

2026年10月6日

QC基準を満たした最後の更新が送信されました

2026年10月5日

最終確認日

2026年10月1日

詳しくは

本研究に関する用語

追加の関連 MeSH 用語

その他の研究ID番号

  • ALCALS

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

いいえ

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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