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

Sponsors

Lead Sponsor: National University of Malaysia

Collaborator: Radboud University

Source National University of Malaysia
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.

Overall Status Recruiting
Start Date February 24, 2020
Completion Date February 23, 2022
Primary Completion Date September 30, 2021
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Changes from Baseline Scale for Ataxia Rating Assessment (SARA) at 3 months and 6 months. Baseline, 3 months, and 6 months
Secondary Outcome
Measure Time Frame
Changes from Baseline Spinocerebellar Ataxia Functional Index (SCAFI) at 3 months and 6 months. Baseline, 3 months, and 6 months
Changes from Baseline Inventory of Non-Ataxia Symptoms (INAS) at 3 months and 6 months. Baseline, 3 months, and 6 months
Changes from Baseline Cerebellar Cognitive & Affective Syndrome (CCAS) Scale at 3 months and 6 months. Baseline, 3 months, and 6 months
Changes from Baseline Wechsler Adult Intelligence Scale (WAIS - 4) at 3 months and 6 months. Baseline, 3 months, and 6 months
Changes from Baseline Delis-Kaplan Executive Function System (D - KEFS) at 3 months and 6 months. Baseline, 3 months, and 6 months
Changes from Baseline Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS Update) at 3 months and 6 months. Baseline, 3 months, and 6 months
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
Enrollment 40
Condition
Intervention

Intervention Type: Dietary Supplement

Intervention Name: Trehalose

Description: A disaccharide sugar usually used as food preservative, but for this study it is given at a higher dose

Arm Group Label: Trehalose

Intervention Type: Dietary Supplement

Intervention Name: Maltose

Description: Maltose power

Arm Group Label: Maltose placebo

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: 85 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Norlinah Mohamed Ibrahim, MRCP Principal Investigator National University of Malaysia
Overall Contact

Last Name: Kah Hui Yap, Master

Phone: +60165536721

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: UKM Medical Centre Kah Hui Yap, Master 0165536721 [email protected]
Location Countries

Malaysia

Verification Date

July 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: National University of Malaysia

Investigator Full Name: Dr Norlinah Mohamed Ibrahim

Investigator Title: Professor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Trehalose

Type: Experimental

Description: Trehalose 100g powder form to be dissolved in water, to be consumed by mouth, every day for 3 months.

Label: Maltose placebo

Type: Placebo Comparator

Description: Malthose 30g powder form to be dissolved in water, to be consumed by mouth, every day for 3 months.

Patient Data No
Study Design Info

Allocation: Randomized

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.

Primary Purpose: Treatment

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.

Source: ClinicalTrials.gov