A Randomised Controlled Trial on the Clinical Efficacy of Oral Trehalose in Patients With Spinocerebellar Ataxia 3: Clinical & FMRI Correlation
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Changes from Baseline Scale for Ataxia Rating Assessment (SARA) at 3 months, 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
研究概览
简要总结
This study evaluates the effectiveness of oral trehalose in alleviating the neuropathological and motor behaviour deficits among patients with SCA3. A total of 40 participants with SCA3 will be recruited, with 20 participants to be administered with trehalose while another 20 participants to be administered with a maltose placebo.
详细描述
Spinocerebellar ataxia 3 (SCA3) is a rare form of inherited neurodegenerative disease involving progressive degeneration of spinocerebellar tract. SCA3 is characterised by increasingly worsening cerebellar function leading to gait abnormalities and poor coordination, dysarthria, and abnormal eye movements. Non-ataxia features include pyramidal and extrapyramidal manifestations, sensorimotor, neuropsychological and psychiatric symptoms. This is attributed to the role of cerebellum in motor, cognitive and affective processing (i.e. cerebellar cognitive and affective syndrome; CCAS), as well as its extensive connection with cerebral structures.
Trehalose is an omnipotent disaccharide molecule found in lower and higher life forms except in vertebrates. It has an amorphous (i.e. non-reducing) property, which is shown in its high hydrophilicity, chemical stability and strong resistance to denaturation / breakdown by heat, acid or enzyme. It is also shown to help refold partially denatured protein, thereby stabilizes protein aggregates, including those of polyglutamine, in vivo as well as in vitro. This has provided an avenue in which trehalose as a therapeutic agent for neurodegenerative disorders with pathological changes of protein aggregates.
In this study, a double-blinded randomised controlled trial (RCT) will be employed. A total of 40 patients with SCA3 will be randomly allocated to oral trehalose group and a placebo group (20 participants for each arm). With regards to clinical outcomes, motor and cognitive performances will be assessed to infer the efficacy of trehalose. Likewise, structural, resting-state fMRI (i.e. functional connectivity), and MR spectroscopy (i.e. metabolism), will be used as imaging biomarkers in this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
Patients with SCA 3 will be randomised into the active treatment group and placebo group to which they are blinded from their group allocation. Likewise, the outcome assessor will be blinded from the patient's group status. A partial unblinding will be made with Group A vs. Group B (rather than the actual grouping) for preliminary analysis on Visit 1 and Visit 2.
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 85 years old.
- •Genetically confirmed SCA 3 diagnosis.
- •Presence of progressive cerebellar syndrome (i.e. symptomatic) and genetic confirmation of SCA 3 in one of the immediate family members with similar clinical syndrome.
- •Able to read, speak, and understand English or Malay.
排除标准
- •Diagnosis of Diabetes Mellitus Type 1 or Type 2
- •Presence of any concomitant neurological condition that might interfere with clinical measures used in this study.
- •Presence of contraindication or hypersensitivity to trehalose.
- •Use of stimulant / medication, caffeine, and tobacco within less than 24 hours washout period prior to assessment and / or scan.
- •Presence of severe visual and / or auditory perceptual deficits.
- •MRI contra-indications: claustrophobia, pregnancy, electronic implants (e.g. pacemaker) in the body, aneurysm clip, and current or past employment as machinists, welders or metal workers.
结局指标
主要结局
Changes from Baseline Scale for Ataxia Rating Assessment (SARA) at 3 months, 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
时间窗: Baseline, 3 months, and 6 months, as well as 3, 6, 9, and 12 months post-treatment follow-up.
An 8-item scale to quantify the severity of ataxia with a scoring of 0 (no ataxia) to 40 (most severe ataxia). Total time taken for test administration is estimated at 10 minutes.
次要结局
- Changes from Baseline Cerebellar Cognitive & Affective Syndrome (CCAS) Scale at 3 months and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.(Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.)
- Changes from Baseline Spinocerebellar Ataxia Functional Index (SCAFI) at 3 months and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.(Baseline, 3 months, and 6 months, as well as 3, 6, 9, and 12 months post-treatment follow-up.)
- Changes from Baseline Wechsler Adult Intelligence Scale (WAIS - 4) at 3 months and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.(Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.)
- Changes from Baseline Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS Update) at 3 months and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.(Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.)
- Changes from Baseline Inventory of Non-Ataxia Symptoms (INAS) at 3 months and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.(Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.)
- Changes from Baseline Resting state fMRI at 3 months.(Baseline and 3 months)
- Changes from Magnetic resonance spectroscopy at 3 months.(Baseline and 3 months)
- Changes from Baseline Delis-Kaplan Executive Function System (D - KEFS) at 3 months and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.(Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.)
研究者
Dr Norlinah Mohamed Ibrahim
Professor
National University of Malaysia