Acetyl-leucine in Post-stroke Ataxia

Official title

The Safety and Efficacy of Acetyl-leucine in Post-stroke Ataxia: a Randomized Placebo-controlled Trial

Overview

Along with the current clinical trial, the efficacy and safety of 4 gram of acetyl-leucine daily for three months in patients with post-stroke ataxia following posterior-circulation ischaemic stroke assessed through BBS, SARA, and mRS, and possible adverse effects.

Detailed description

the investigators will conduct our double-blinded, placebo-controlled, parallel-group trial in Kafr-Elsheikh University in the time between 1st January 2026 to 1st July 2026.

the study will include 200 post-circulation AIS patients who will undergo randomization and divided into two groups; The (A) group, which consisted of 100 patients who administered (a 4 gram of acetyl-leucine per day) and the (B) group, which had 100 patients who administered a placebo during the first 24 hours of stroke onset and for 3 months.

Both groups received (open-label 300 mg loading dose aspirin and 300 mg loading clopidogrel during the first 24 hours of stroke onset, followed by 75 mg clopidogrel and 100 mg aspirin once daily from the 2nd to the 90th day.

The diagnosis of ischemic stroke was established through a detailed clinical history and examination and suitable brain imaging. All of the patients had CT of the brain and CT angiography (CTA) including the aortic arch through the circle of Willis before thrombolysis; the CT of the brain was performed on the 64-slice dual-source spiral CT scanner of Somatom definition by Siemens, and the supratentorial compartment scans were imaged with 5-8mm contiguous sections and the brain stem and cerebellum scans were imaged with 3-5mm slices, and we obtained eighteen images for each series. After thrombolysis, all of the patients underwent an MRI brain on a 1.5 T (Siemens Essenza) MR system, stroke protocol: T1W, T2W, fluid attenuation inversion recovery imaging (FLAIR), diffusion-weighted imaging (DWI), T2 Echo Gradient, and MRA brain \& neck time of flight (TOF) if CTA was contraindicated; the investigators performed an additional brain CT scan after 24-36 hours to evaluate hemorrhagic transformation. (8), and considered hemorrhagic transformation symptomatic if the NIHSS score increased by 4 points or more. (9) The computed tomography (CT)/ magnetic resonance imaging (MRI) examinations were assessed in our study by two highly experienced professionals: a senior stroke physician and a senior radiologist.

the investigators identified posterior-circulation stroke (PCS) when ischemic occlusion affected basilar, posterior cerebral or vertebral arteries

Interventions

• Drug Acetyl-Leucine
  The acetyl-leucine arm will receive (a 4 gram of acetyl-leucine daily for three months and an open-label loading 300 mg aspirin and 300 mg clopidogrel during the first 24 hours of stroke, followed by a maintenance dose of 100 mg aspirin and 75 mg clopidogrel.
• Drug Placebo
  The placebo arm will receive (a 4 gram of placebo daily for three months and an open-label loading 300 mg aspirin and 300 mg clopidogrel during the first 24 hours of stroke, followed by a maintenance dose of 100 mg aspirin and 75 mg clopidogrel.
• Drug Clopidogrel 75 Mg Oral Tablet
  All patients received an open-label loading 300 mg clopidogrel during the first 24 hours of stroke, followed by a maintenance dose of 75 mg clopidogrel once daily.
• Drug aspirin 100mg
  All patients received an open-label loading 300 mg aspirin during the first 24 hours of stroke, followed by a maintenance dose of 100 mg aspirin once daily.

Primary outcome measures

• value of the Berg balance scale (BBS) [Time frame: 90 days]
• the rate of participants who suffered from treatment-related side effects [Time frame: 90 days]

Secondary outcome measures (2)

• value of Scale for the Assessment and Rating of Ataxia (SARA) [Time frame: 90 days]
• value of Modified Rankin Scale(mRS) at three months [Time frame: 90 days]

Eligibility criteria

Inclusion criteria

• the investigators included both males and females, aged between 18 and 80 years, who experienced their first-ever posterior-circulation ischaemic stroke and presented with gait ataxia and score at least 1 point on the items gait, stance, trunk or heel-shin-slide of the Scale for the Assessment and Rating of Ataxia (SARA) and 47 points or less on the Berg Balance Scale (BBS).
• All of our patients underwent randomisation during the first 24 hours of the symptoms' onset, and within the first 24 hours from the time at which the patient's condition was last reported to be normal for wake-up stroke patients.

Exclusion criteria

• the investigators excluded patients with modified Rankin Scale (mRS) score of 5 or more, physical or mental conditions that would not allow safe participation in the study or would influence the assessment of outcomes (e.g., dementia, disturbed conscious level, severe aphasia, etc.).
• the investigators ruled out participants who suffered from neurological diseases associated with recurrent neurological deficits, such as (epilepsy, multiple sclerosis, head trauma followed by neurological deficit).
• the investigators excluded participants who underwent intravenous thrombolysis, carotid, cerebrovascular, or coronary revascularization during the first week of the trial to avoid clouding of efficacy and safety analysis.
• the investigators excluded patients who experienced recurrent ischemic stroke detected from their clinical data and/or magnetic resonance imaging (MRI) brain findings. In addition, we excluded participants who experienced hypersensitivity to the study treatment
• the investigators excluded participants who experienced organ failure such as renal failure and liver cell failure, active malignancies, and patients with a known bleeding diathesis or coagulation disorder, a history of intracerebral hemorrhage, gastrointestinal bleeding within the past 6 months, or major surgery within 30 days before randomisation .

the investigators excluded pregnant and lactating women, patients with cerebral venous thrombosis, and patients with stroke associated with cardiac arrest.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Egypt · 1 center

• Kafr Elsheikh University Hospital — Kafr ash Shaykh

Publications

• Paciaroni M, Ince B, Hu B, Jeng JS, Kutluk K, Liu L, Lou M, Parfenov V, Wong KSL, Zamani B, Paek D, Min Han J, Del Aguila M, Girotra S. Benefits and Risks of Clopidogrel vs. Aspirin Monotherapy after Recent Ischemic Stroke: A Systematic Review and Meta-Analysis. Cardiovasc Ther. 2019 Dec 1;2019:1607181. doi: 10.1155/2019/1607181. eCollection 2019. PMID 31867054
• Lipton RB, Liberman JN, Kolodner KB, Bigal ME, Dowson A, Stewart WF. Migraine headache disability and health-related quality-of-life: a population-based case-control study from England. Cephalalgia. 2003 Jul;23(6):441-50. doi: 10.1046/j.1468-2982.2003.00546.x. PMID 12807523

Identifiers

NCT: NCT07275749 · 19012025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗