Efficacy Of Oral Trehalose In Spinocerebellar Ataxia 3

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Sponsorlar

National University of Malaysia

Əməkdaşlar

Radboud University

KLINIK SINAQ: NCT04399265

BioSeek: nct04399265

Açar sözlər

Mücərrəd

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.

Təsvir

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.

Tarixlər

Son Doğrulandı:	06/30/2020
İlk təqdim:	03/10/2020
Təxmini qeydiyyat təqdim edildi:	05/20/2020
İlk Göndərmə:	05/21/2020
Son Yeniləmə Göndərildi:	07/07/2020
Son Yeniləmə Göndərildi:	07/09/2020
Həqiqi Təhsilin Başlama Tarixi:	02/23/2020
Təxmini İlkin Tamamlanma Tarixi:	09/29/2021
Təxmini İşin Tamamlanma Tarixi:	02/22/2022

Vəziyyət və ya xəstəlik

Spinocerebellar Ataxia Type 3

Müdaxilə / müalicə

Dietary Supplement: Trehalose

Dietary Supplement: Maltose placebo

Faza

Qol Qrupları

Qol	Müdaxilə / müalicə
Experimental: Trehalose Trehalose 100g 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 Malthose 30g powder form to be dissolved in water, to be consumed by mouth, every day for 3 months.	Dietary Supplement: Maltose placebo Maltose power

Uyğunluq Kriteriyaları

Təhsil üçün uyğun yaşlar	18 Years Üçün 18 Years
Təhsilə Uyğun Cinslər	All
Sağlam Könüllüləri qəbul edir	Bəli
Kriteriyalar	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.

Nəticə

İlkin nəticə tədbirləri

1. Changes from Baseline Scale for Ataxia Rating Assessment (SARA) at 3 months and 6 months. [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.

İkincili Nəticə Tədbirləri

1. Changes from Baseline Spinocerebellar Ataxia Functional Index (SCAFI) at 3 months and 6 months. [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.

2. Changes from Baseline Inventory of Non-Ataxia Symptoms (INAS) at 3 months and 6 months. [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.

3. Changes from Baseline Cerebellar Cognitive & Affective Syndrome (CCAS) Scale at 3 months and 6 months. [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.

4. Changes from Baseline Wechsler Adult Intelligence Scale (WAIS - 4) at 3 months and 6 months. [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

5. Changes from Baseline Delis-Kaplan Executive Function System (D - KEFS) at 3 months and 6 months. [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.

6. 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]

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.

7. Changes from Baseline Resting state fMRI at 3 months. [Baseline and 3 months]

The level of measurement of oxy-Hb (activation level) is continuous; greater oxy-Hb (mM.mm) indicates greater activation.

8. Changes from Magnetic resonance spectroscopy at 3 months. [Baseline and 3 months]

The level of measurement of N-Acetyl Aspartate (NAA; metabolism) is continuous; greater NAA (ppm) indicates greater metabolism.

Digər nəticə tədbirləri

1. Changes from Baseline Structural / T1 MRI at 3 months. [Baseline and 3 months]

The level of measurement of grey matter density (structural) is continuous; greater grey matter density indicates greater structural volume.

2. Changes from Baseline Situational Motivation Scale (SIMS) at 3 months and 6 months. [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.

3. Changes from Baseline EuroQol-5D 3L (EQ-5D-3L) at 3 months and 6 months. [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.

4. Adverse event [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.

Efficacy Of Oral Trehalose In Spinocerebellar Ataxia 3

Açar sözlər

maltoza

trehalose

atrofiya

neurodegenerative diseases

machado-joseph disease

ataksiya

dysarthria

disaccharide

alpha maltose

mantar