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

Phase 3TerminatedNCT03901638

National Taiwan University Hospital18 enrolled

Overview

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.

The study is terminated prematurely due to project replanning and difficulty in recruitment during the pandemic. The overall sample size is not adequate to meet the requirement of estimated power. The statistical results will be investigated. No severe drug-related adverse events were reported during the study period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Ataxia, Cerebellar Multiple System Atrophy

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

=Scale for the assessment and rating of ataxia (SARA) score

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.