Effects of acetyl-dl-leucine in patients with cerebellar ataxia: a case series

Strupp, Michael; Teufel, Julian; Habs, M.; Feuerecker, Regina; Muth, Carolin; Warrenburg, Bart P. van de; Klopstock, Thomas; Feil, Katharina

doi:10.1007/s00415-013-7016-x

Cited by 89 publications

(57 citation statements)

References 21 publications

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“…The sample size was calculated on the basis of the primary hypothesis, using our own preliminary case series data (13 patients [17]) and a similar placebo-controlled trial (20 patients [7]) investigating the efficacy of varenicline on the change in SARA total score in patients with SCA 3. Hence, assuming a minimum clinically relevant difference in the SARA total score of 1.5 points [25] to be detected (i.e.…”

Section: Methodsmentioning

confidence: 99%

“…In a first case series on 13 patients with different types of hereditary and non-hereditary non-acquired CA, we reported positive effects of acetyl-DL-leucine (5 g per day for one week) on the motor function measured by the Scale for the Assessment and Rating of Ataxia (SARA) and the Spinocerebellar Ataxia Functional Index (SCAFI) [17]. The agent was well tolerated [17].…”

Section: Introductionmentioning

confidence: 99%

“…The agent was well tolerated [17]. Mean total SARA decreased from 16.1 ± 7.1 (mean ± SD) at baseline to 12.8 ± 6.8 after one week on medication ( p = 0.002), and patients showed better performance in the SCAFI consisting of the 8-m-walking-time (8 MW), 9-Hole-Peg-Test of the dominant hand (9HPTD) and the PATA rate task (timed speech task where the patient is asked to repeat “PATA” as quickly and distinctly as possible for 10 s two times).…”

Section: Introductionmentioning

confidence: 99%

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Effects of acetyl-DL-leucine on cerebellar ataxia (ALCAT trial): study protocol for a multicenter, multinational, randomized, double-blind, placebo-controlled, crossover phase III trial

et al. 2017

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BackgroundCerebellar ataxia (CA) is a frequent and often disabling condition that impairs motor functioning and impacts on quality of life (QoL). No medication has yet been proven effective for the symptomatic or even causative treatment of hereditary or non-hereditary, non-acquired CA. So far, the only treatment recommendation is physiotherapy. Therefore, new therapeutic options are needed. Based on three observational studies, the primary objective of the acetyl-DL-leucine on ataxia (ALCAT) trial is to examine the efficacy and tolerability of a symptomatic therapy with acetyl-DL-leucine compared to placebo on motor function measured by the Scale for the Assessment and Rating of Ataxia (SARA) in patients with CA.Methods/DesignAn investigator-initiated, multicenter, European, randomized, double-blind, placebo-controlled, 2-treatment 2-period crossover phase III trial will be carried out. In total, 108 adult patients who meet the clinical criteria of CA of different etiologies (hereditary or non-hereditary, non-acquired) presenting with a SARA total score of at least 3 points will be randomly assigned in a 1:1 ratio to one of two different treatment sequences, either acetyl-DL-leucine (up to 5 g per day) followed by placebo or vice versa. Each sequence consists of two 6-week treatment periods, separated by a 4-week wash-out period. A follow-up examination is scheduled 4 weeks after the end of treatment. The primary efficacy outcome is the absolute change in the SARA total score. Secondary objectives are to demonstrate that acetyl-DL-leucine is effective in improving (1) motor function measured by the Spinocerebellar Ataxia Functional Index (SCAFI) and SARA subscore items and (2) QoL (EuroQoL 5 dimensions and 5 level version, EQ-5D-5 L), depression (Beck Depression Inventory, BDI-II) and fatigue (Fatigue Severity Score, FSS). Furthermore, the incidence of adverse events will be investigated.DiscussionThe results of this trial will inform whether symptomatic treatment with the modified amino-acid acetyl-DL-leucine is a worthy candidate for a new drug therapy to relieve ataxia symptoms and to improve patient care. If superiority of the experimental drug to placebo can be established it will also be re-purposing of an agent that has been previously used for the symptomatic treatment of dizziness.Trial registrationThe trial was prospectively registered at www.clinicaltrialsregister.eu (EudraCT no. 2015–000460–34) and at https://www.germanctr.de (DRKS-ID: DRKS00009733).

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of acetyl-DL-leucine on cerebellar ataxia (ALCAT trial): study protocol for a multicenter, multinational, randomized, double-blind, placebo-controlled, crossover phase III trial

et al. 2017

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“…Acetyl- dl -leucine (Tanganil™) has been widely used in France for symptomatic treatment of vertigo and dizziness. Recently, 13 patients with cerebellar ataxia of different etiologies (SCA1/2, ADCA, AOA, SAOA) were treated with acetyl- dl -leucine (5 g/day) for 1 week in an open label case series [73]. Mean SARA score decreased by about four points.…”

Section: Drug Therapy For Cerebellar Ataxiamentioning

confidence: 99%

“…In all other situations, there is no medication which is of reliable and reproducible help in patients with cerebellar ataxia. Some drugs appear to be promising, particularly acetyl- dl -leucine and chlorzoxazone, but effects need to be verified in large controlled trials [23, 73]. There is consensus that, as yet, treatment is largely limited to physiotherapy, speech therapy, and occupational therapy.…”

Section: Consensus and Future Directionsmentioning

confidence: 99%

Consensus Paper: Management of Degenerative Cerebellar Disorders

et al. 2013

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Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized. There is consensus that up to date, no medication has been proven effective. Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy. For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non-invasive brain stimulation.

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Safety and Efficacy of Acetyl-DL-Leucine in Certain Types of Cerebellar Ataxia

et al. 2021

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Key Points Question Is the modified amino acid acetyl-DL-leucine effective and safe in patients with cerebellar ataxia of different etiologies? Findings In this randomized clinical crossover trial including 108 patients with cerebellar ataxia, a 6-week treatment with acetyl-DL-leucine was not effective. Adverse events were mild. Meaning This study’s findings suggest that further symptom-oriented trials evaluating the long-term effects of acetyl-DL-leucine for well-defined subgroups of cerebellar ataxia are needed.

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Effects of acetyl-dl-leucine in patients with cerebellar ataxia: a case series

Cited by 89 publications

References 21 publications

Effects of acetyl-DL-leucine on cerebellar ataxia (ALCAT trial): study protocol for a multicenter, multinational, randomized, double-blind, placebo-controlled, crossover phase III trial

Effects of acetyl-DL-leucine on cerebellar ataxia (ALCAT trial): study protocol for a multicenter, multinational, randomized, double-blind, placebo-controlled, crossover phase III trial

Consensus Paper: Management of Degenerative Cerebellar Disorders

Safety and Efficacy of Acetyl-DL-Leucine in Certain Types of Cerebellar Ataxia

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