Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy

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StatusRecruiting

Keywords

Abstract

Multiple system atrophy (MSA) is a fetal, rare neurodegenerative disease presenting with parksinonism, autonomic dysfunction, and cerebellar ataxia. Numerous anti-parkinsonism agents have been developed. However, no medication has yet been proven effective for the symptomatic or even causative treatment in cerebellar ataxia. To our knowledge, cerebellar N-methyl-D- aspartic acid (NMDA) receptors play a special role in the modulation of motor learning and coordination. Tllsh2910, a NMDA modulator, has been found to attenuate the ataxic gait in the mouse model. Here, we designed a large-scale double-blind randomized controlled, cross-over phase III trial to investigate the efficacy of Tllsh2910 in neurodegenerative ataxic patients and the association of gut microbiota change.

Dates

Last Verified:	02/28/2019
First Submitted:	03/23/2019
Estimated Enrollment Submitted:	04/01/2019
First Posted:	04/02/2019
Last Update Submitted:	04/01/2019
Last Update Posted:	04/02/2019
Actual Study Start Date:	04/01/2019
Estimated Primary Completion Date:	11/14/2021
Estimated Study Completion Date:	11/14/2021

Condition or disease

Ataxia, Cerebellar

Multiple System Atrophy

Intervention/treatment

Drug: Tllsh2910

Drug: Placebo

Phase

Phase 3

Arm Groups

Arm	Intervention/treatment
Experimental: Tllsh2910 to placebo Tllsh2910 160mg per day for 12 weeks with wash-out period 12 weeks and subsequent placebos for 12 weeks.
Experimental: Placebo to Tllsh2910 Placebos for 12 weeks with wash-out period 12 weeks and subsequent Tllsh2910 160mg per day for 12 weeks

Eligibility Criteria

Ages Eligible for Study	18 Years To 18 Years
Sexes Eligible for Study	All
Accepts Healthy Volunteers	Yes
Criteria	Inclusion Criteria: - 1. Clinically confirmed cerebellar ataxia with a SARA total score ≥ 3 (range 0-40). - 2. Clinical diagnosis of probable or possible MSA-C. - 3. Patients older than 18 years old and younger than 80 years old. Exclusion Criteria: - 1. Major systemic diseases such as hepatic, renal or heart failure, malignancy, stroke. - 2. Concomitant medication which inhibit CYP2C19 enzyme such as Clopidogrel, cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, fluoxetine, fluvoxamine, ticlopidine. - 3. Pregnancy and/or breastfeeding. - 4. Acute diseases that might interfere with the trial.

Outcome

Primary Outcome Measures

1. =Scale for the assessment and rating of ataxia (SARA) score [Baseline, 12 weeks, 24 weeks, 36 weeks]

SARA is an 8-item performance based scale with gait, stance, sitting, speech disturbance, finger chase, nose-finger test, fast alternative hand movements, and heel-shin slide, yielding a total score of 0 (no ataxia) to 40 (most severe ataxia). The change in the SARA score will be recorded from period-level baseline to the end of the 12-week, 24-week, 36-week treatment period.

Secondary Outcome Measures

1. International Cooperative Ataxia Rating Scale (ICARS) score [Baseline, 12 weeks, 24 weeks, 36 weeks]

ICARS is an 19-item performance based scale with 4 subscales of postural and gait disturbances, kinetic function, speech disorders, and oculomotor disorders, yielding a total score of 0 (no ataxia) to 100 (most severe ataxia). The change in the ICARS score will be measured from period-level baseline to the end of the 12-week, 24-week, 36-week treatment period.

2. Unified multiple system atrophy rating scale (UMSARS) Part II score [Baseline, 12 weeks, 24 weeks, 36 weeks]

UMSARS is an validated 26-items scale for multiple system atrophy with 4 subscales of historical review, motor examination scale, autonomic examination, and global disability scale. The Part II is a performance based subscale, yield a total score of 0 (no motor impairment) to 56 (most severe motor impairment). The change in the UMSARS Part-II score will be measured from period-level baseline to the end of the 12-week, 24-week, 36-week treatment period.

3. The composition change of gut microbiota [Baseline, 12 weeks]

The gut microbiota will be measured at baseline and 12th weeks.

4. The change of total time needed for a 8-meter walking test [Baseline, 12 weeks, 24 weeks, 36 weeks]

Total time of 8-meter walking test will be measured from period-level baeline to the end of the 12-week, 24-week, and 36-week.

5. The change of the World Health Organization Quality of Life (WHOQOL-BREF) scale [Baseline, 12 weeks, 24 weeks, 36 weeks]

The WHOQOL-BREF scale is a 28-item questionnaire about quality of life. The change of WHOQOL-BREF scores will be measured at baseline, 12-week, 24-week, and 36-week.

6. The total time needed for 9 hole peg test [Baseline, 12 weeks, 24 weeks, 36 weeks]

The total time needed for 9 hole peg test will be measured at the baseline, 12-week, 24-week, and 36-week.

Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy

Keywords

atrophy

neurodegenerative diseases

ataxia

aspartic acid