Efficacy Of Oral Trehalose In Spinocerebellar Ataxia 3
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|ClinicalTrials.gov Identifier: NCT04399265|
Recruitment Status : Recruiting
First Posted : May 22, 2020
Last Update Posted : September 11, 2020
|Condition or disease||Intervention/treatment||Phase|
|Spinocerebellar Ataxia Type 3||Dietary Supplement: Trehalose Dietary Supplement: Maltose||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||This study will employ a double-blind randomised controlled trial (RCT) with two arms. Patients with SCA3 will be randomly allocated to oral trehalose group and a maltose placebo group. A total of 20 participants will be allocated to each group. There is a possibility of including other types of SCA at later stage of the study.|
|Masking:||Double (Participant, Outcomes Assessor)|
|Masking Description:||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.|
|Official Title:||A Randomised Controlled Trial on the Clinical Efficacy of Oral Trehalose in Patients With Spinocerebellar Ataxia 3: Clinical & FMRI Correlation|
|Actual Study Start Date :||February 24, 2020|
|Estimated Primary Completion Date :||September 30, 2021|
|Estimated Study Completion Date :||February 23, 2022|
Trehalose powder form to be dissolved in water, to be consumed by mouth, every day for 3 months.
Dietary Supplement: Trehalose
A disaccharide sugar usually used as food preservative, but for this study it is given at a higher dose
Placebo Comparator: Maltose placebo
Isocaloric maltose powder form to be dissolved in water, to be consumed by mouth, every day for 3 months.
Dietary Supplement: Maltose
- Changes from Baseline Scale for Ataxia Rating Assessment (SARA) at 3 months and 6 months. [ Time Frame: Baseline, 3 months, and 6 months ]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.
- Changes from Baseline Spinocerebellar Ataxia Functional Index (SCAFI) at 3 months and 6 months. [ Time Frame: Baseline, 3 months, and 6 months ]A validated multi-modal assessment tool that is composed of: a) timed 8 metre walk (8MW); b) the 9-hole peg test (9HPT); and c) the rate of "PATA" repetition over 10 seconds (PATA) to rate speech performance. Total time taken for test administration is estimated at 10 minutes.
- Changes from Baseline Inventory of Non-Ataxia Symptoms (INAS) at 3 months and 6 months. [ Time Frame: Baseline, 3 months, and 6 months ]A validated scale assessing non-cerebellar signs with a scoring of 0 (no non-ataxia sign) to 16 (all assessed systems affected). Total time taken for test administration is estimated at 10 minutes.
- Changes from Baseline Cerebellar Cognitive & Affective Syndrome (CCAS) Scale at 3 months and 6 months. [ Time Frame: Baseline, 3 months, and 6 months ]CCAS Scale is a brief cognitive screening tool to help identify CCAS in patients with cerebellar impairment. It derives a total score of 120 as a continuous measure; as well as an ordinal measure in accordance to the number of failed tests: 1) Possible CCAS = 1 failed test; 2) Probable CCAS = 2 failed tests; Definite CCAS = 3 or more failed tests. Four different forms were available to minimize the practice effect. Total time taken for test administration is estimated at 10 minutes.
- Changes from Baseline Wechsler Adult Intelligence Scale (WAIS - 4) at 3 months and 6 months. [ Time Frame: Baseline, 3 months, and 6 months ]WAIS - 4 is an IQ test designed to measure intelligence and cognitive ability in adults and older adolescents. The selected subtests are Matrix Reasoning, Digit Span, and Coding. These subtests are used to measure abstract reasoning, WM, and processing speed respectively. These index and subtests have good reliability
- Changes from Baseline Delis-Kaplan Executive Function System (D - KEFS) at 3 months and 6 months. [ Time Frame: Baseline, 3 months, and 6 months ]D - KEFS is a neuropsychological battery designed to measure various subdomains of executive function from 8 - 89 years old. The selected subtests are: Tower Test, Trail Making Test (TMT), Colour-Word Interference Test (CWIT). These tests measure planning, set-shifting, and inhibition abilities respectively.
- Changes from Baseline Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS Update) at 3 months and 6 months. [ Time Frame: Baseline, 3 months, and 6 months ]RBANS Update is a neuropsychological battery designed to measure 5 neuropsychological domains from 12:0 - 89:11 years old. The selected subtests are: Figure Copy and Figure Recall. These tests measure visual construction, visual memory, and language abilities respectively.
- Changes from Baseline Resting state fMRI at 3 months. [ Time Frame: Baseline and 3 months ]The level of measurement of oxy-Hb (activation level) is continuous; greater oxy-Hb (mM.mm) indicates greater activation.
- Changes from Magnetic resonance spectroscopy at 3 months. [ Time Frame: Baseline and 3 months ]The level of measurement of N-Acetyl Aspartate (NAA; metabolism) is continuous; greater NAA (ppm) indicates greater metabolism.
- Changes from Baseline Structural / T1 MRI at 3 months. [ Time Frame: Baseline and 3 months ]The level of measurement of grey matter density (structural) is continuous; greater grey matter density indicates greater structural volume.
- Changes from Baseline Situational Motivation Scale (SIMS) at 3 months and 6 months. [ Time Frame: Baseline, 3 months, and 6 months ]SIMS comprises 16 items on four subscales, Intrinsic motivation (e.g., "I think that this activity is interesting"), Identified regulation (e.g., "I am doing it for my own good"), External regulation (e.g., "I am supposed to do it") and Amotivation (e.g., "I don't see what this activity brings me"). It contains 4 items per subscale scored on a scale from 1 to 7 providing a score between 4 and 28 for each subscale. It has an internal reliability of α = .74 - .83 for the four subscales. Total time taken for test administration is estimated at 5 minutes.
- Changes from Baseline EuroQol-5D 3L (EQ-5D-3L) at 3 months and 6 months. [ Time Frame: Baseline, 3 months, and 6 months ]EQ-5D-3L consists of 2 parts: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). EQ-5D has 5 dimensions of assessment (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). Each dimension has 3 levels (ordinal): no problem, some problem, and extreme problem. It has an internal reliability of α = .83 and valid among clinically and demographically heterogeneous patients. Total time taken for test administration is estimated at 5 minutes.
- Adverse event [ Time Frame: Baseline, 3 motnhs, and 6 months ]Adverse event will be recorded in terms of severity, study intervention relationship, action taken regarding study intervention, outcome of adverse event, expected, and serious adverse event.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04399265
|Contact: Kah Hui Yap, Masteremail@example.com|
|Contact: Norlinah Mohamed Ibrahim, MRCPfirstname.lastname@example.org|
|Principal Investigator:||Norlinah Mohamed Ibrahim, MRCP||National University of Malaysia|