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@ARTICLE{Feil:163389,
      author       = {Feil, Katharina and Adrion, Christine and Boesch, Sylvia
                      and Doss, Sarah and Giordano, Ilaria and Hengel, Holger and
                      Jacobi, Heike and Klockgether, Thomas and Klopstock, Thomas
                      and Nachbauer, Wolfgang and Schöls, Ludger and Steiner,
                      Katharina Marie and Stendel, Claudia and Timmann, Dagmar and
                      Naumann, Ivonne and Mansmann, Ulrich and Strupp, Michael},
      collaboration = {Group, ALCAT Study},
      title        = {{S}afety and {E}fficacy of {A}cetyl-{DL}-{L}eucine in
                      {C}ertain {T}ypes of {C}erebellar {A}taxia: {T}he {ALCAT}
                      {R}andomized {C}linical {C}rossover {T}rial.},
      journal      = {JAMA network open},
      volume       = {4},
      number       = {12},
      issn         = {2574-3805},
      address      = {Chicago, Ill.},
      publisher    = {American Medical Association},
      reportid     = {DZNE-2022-00151},
      pages        = {e2135841},
      year         = {2021},
      note         = {(CC BY)},
      abstract     = {Cerebellar ataxia is a neurodegenerative disease impairing
                      motor function characterized by ataxia of stance, gait,
                      speech, and fine motor disturbances.To investigate the
                      efficacy, safety, and tolerability of the modified essential
                      amino acid acetyl-DL-leucine in treating patients who have
                      cerebellar ataxia.The Acetyl-DL-leucine on Cerebellar Ataxia
                      (ALCAT) trial was an investigator-initiated, multicenter,
                      double-blind, randomized, placebo-controlled, clinical
                      crossover trial. The study was conducted at 7 university
                      hospitals in Germany and Austria between January 25, 2016,
                      and February 17, 2017. Patients were aged at least 18 years
                      and diagnosed with cerebellar ataxia of hereditary
                      (suspected or genetically confirmed) or nonhereditary or
                      unknown type presenting with a total score of at least 3
                      points on the Scale for the Assessment and Rating of Ataxia
                      (SARA). Statistical analysis was performed from April 2018
                      to June 2018 and January 2020 to March 2020.Patients were
                      randomly assigned (1:1) to receive acetyl-DL-leucine orally
                      (5 g per day after 2 weeks up-titration) followed by a
                      matched placebo, each for 6 weeks, separated by a 4-week
                      washout, or vice versa. The randomization was done via a
                      web-based, permuted block-wise randomization list (block
                      size, 2) that was stratified by disease subtype (hereditary
                      vs nonhereditary or unknown) and site.Primary efficacy
                      outcome was the absolute change of SARA total score from
                      (period-dependent) baseline to week 6.Among 108 patients who
                      were randomly assigned to sequence groups (54 patients
                      each), 55 $(50.9\%)$ were female; the mean (SD) age was 54.8
                      (14.4) years; and the mean (SD) SARA total score was 13.33
                      (5.57) points. The full analysis set included 105 patients
                      (80 patients with hereditary, 25 with nonhereditary or
                      unknown cerebellar ataxia). There was no evidence of a
                      difference in the mean absolute change from baseline to week
                      6 in SARA total scores between both treatments (mean
                      treatment difference: 0.23 points $[95\%$ CI, -0.40 to 0.85
                      points]).In this large multicenter, double-blind,
                      randomized, placebo-controlled clinical crossover trial,
                      acetyl-DL-leucine in the investigated dosage and treatment
                      duration was not superior to placebo for the symptomatic
                      treatment of certain types of ataxia. The drug was well
                      tolerated; and ALCAT yielded valuable information about the
                      duration of treatment periods and the role of placebo
                      response in cerebellar ataxia. These findings suggest that
                      further symptom-oriented trials are needed for evaluating
                      the long-term effects of acetyl-DL-leucine for well-defined
                      subgroups of cerebellar ataxia.EudraCT 2015-000460-34.},
      keywords     = {Administration, Oral / Adult / Aged / Cerebellar Ataxia:
                      classification / Cerebellar Ataxia: drug therapy /
                      Cross-Over Studies / Double-Blind Method / Drug
                      Administration Schedule / Female / Humans / Leucine:
                      administration $\&$ dosage / Leucine: analogs $\&$
                      derivatives / Male / Middle Aged / Treatment Outcome /
                      Leucine (NLM Chemicals) / acetylleucine (NLM Chemicals)},
      cin          = {Patient studies, Bonn / AG Gasser 1 / AG Klockgether / AG
                      Höglinger 2 / AG Höglinger 1},
      ddc          = {610},
      cid          = {I:(DE-2719)1011101 / I:(DE-2719)1210000 /
                      I:(DE-2719)1011001 / I:(DE-2719)1111015 /
                      I:(DE-2719)1110002},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34905009},
      pmc          = {pmc:PMC8672236},
      doi          = {10.1001/jamanetworkopen.2021.35841},
      url          = {https://pub.dzne.de/record/163389},
}