- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04399265
Efficacy Of Oral Trehalose In Spinocerebellar Ataxia 3
A Randomised Controlled Trial on the Clinical Efficacy of Oral Trehalose in Patients With Spinocerebellar Ataxia 3: Clinical & FMRI Correlation
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Kah Hui Yap, Master
- Phone Number: +60165536721
- Email: kahhui0411@gmail.com
Study Contact Backup
- Name: Norlinah Mohamed Ibrahim, MRCP
- Phone Number: +60122145306
- Email: norlinah@ppukm.ukm.edu.my
Study Locations
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Kuala Lumpur
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Cheras, Kuala Lumpur, Malaysia, 56000
- Recruiting
- UKM Medical Centre
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Contact:
- Norlinah Mohamed Ibrahim, MRCP
- Phone Number: +60122145306
- Email: norlinah@ppukm.ukm.edu.my
-
Contact:
- Kah Hui Yap, Master
- Phone Number: 0165536721
- Email: kahhui0411@gmail.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Trehalose
Trehalose powder form to be dissolved in water, to be consumed by mouth, every day for 3 months.
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A disaccharide sugar usually used as food preservative, but for this study it is given at a higher dose
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Placebo Comparator: Maltose placebo
Isocaloric maltose powder form to be dissolved in water, to be consumed by mouth, every day for 3 months.
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Maltose power
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
Time Frame: Baseline, 3 months, and 6 months, as well as 3, 6, 9, and 12 months post-treatment follow-up.
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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.
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Baseline, 3 months, and 6 months, as well as 3, 6, 9, and 12 months post-treatment follow-up.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
Time Frame: Baseline, 3 months, and 6 months, as well as 3, 6, 9, and 12 months post-treatment follow-up.
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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.
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Baseline, 3 months, and 6 months, as well as 3, 6, 9, and 12 months post-treatment follow-up.
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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.
Time Frame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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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.
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Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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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.
Time Frame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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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.
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Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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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.
Time Frame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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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
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Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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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.
Time Frame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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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.
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Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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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.
Time Frame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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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.
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Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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Changes from Baseline Resting state fMRI at 3 months.
Time Frame: Baseline and 3 months
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The level of measurement of oxy-Hb (activation level) is continuous; greater oxy-Hb (mM.mm) indicates greater activation.
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Baseline and 3 months
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Changes from Magnetic resonance spectroscopy at 3 months.
Time Frame: Baseline and 3 months
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The level of measurement of N-Acetyl Aspartate (NAA; metabolism) is continuous; greater NAA (ppm) indicates greater metabolism.
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Baseline and 3 months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes from Baseline Structural / T1 MRI at 3 months.
Time Frame: Baseline and 3 months
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The level of measurement of grey matter density (structural) is continuous; greater grey matter density indicates greater structural volume.
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Baseline and 3 months
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Changes from Baseline Situational Motivation Scale (SIMS) at 3 months and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
Time Frame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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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.
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Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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Changes from Baseline EuroQol-5D 3L (EQ-5D-3L) at 3 months and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
Time Frame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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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.
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Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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Adverse event
Time Frame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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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.
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Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Norlinah Mohamed Ibrahim, MRCP, National University of Malaysia
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Genetic Diseases, Inborn
- Neurodegenerative Diseases
- Dyskinesias
- Spinal Cord Diseases
- Heredodegenerative Disorders, Nervous System
- Cerebellar Diseases
- Ataxia
- Cerebellar Ataxia
- Spinocerebellar Ataxias
- Spinocerebellar Degenerations
- Machado-Joseph Disease
Other Study ID Numbers
- DIP-2019-007
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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