Clinical trial NCT04399265: Efficacy Of Oral Trehalose In Spinocerebellar Ataxia 3
Official title: A Randomised Controlled Trial on the Clinical Efficacy of Oral Trehalose in Patients With Spinocerebellar Ataxia 3: Clinical & FMRI Correlation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Spinocerebellar Ataxia Type 3
Keywords: Spinocerebellar ataxia Type 3
Cerebellar Cognitive and Affective Syndrome
Trehalose
Neuropsychology
Magnetic resonance imaging
Lead sponsor: National University of Malaysia
Sponsor class: OTHER
Collaborators: name: Radboud University Medical Center
First posted: 2020-05-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Baseline, 3 months, and 6 months, as well as 3, 6, 9, and 12 months post-treatment follow-up.
Secondary outcomes:
measure: 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.
timeFrame: Baseline, 3 months, and 6 months, as well as 3, 6, 9, and 12 months post-treatment follow-up.
measure: 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.
timeFrame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
measure: 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.
timeFrame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
measure: 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.
timeFrame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
measure: 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.
timeFrame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
measure: 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.
timeFrame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
measure: Changes from Baseline Resting state fMRI at 3 months.
timeFrame: Baseline and 3 months
measure: Changes from Magnetic resonance spectroscopy at 3 months.
timeFrame: Baseline and 3 months
Other outcomes:
measure: Changes from Baseline Structural / T1 MRI at 3 months.
timeFrame: Baseline and 3 months
measure: 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.
timeFrame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
measure: 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.
timeFrame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
measure: Adverse event
timeFrame: Baseline, 3 months, and 6 months; as well as 3, 6, 9, and 12 months post-treatment follow-up.
Locations:
city: Cheras
country: Malaysia
facility: UKM Medical Centre
state: Kuala Lumpur
Study officials:
affiliation: National University of Malaysia
name: Norlinah Mohamed Ibrahim, MRCP
role: PRINCIPAL_INVESTIGATOR
References: