Clinical trial NCT03901638: Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy
Official title: Gut Microbiota Alteration and Improvement of Ataxia in Patients of Multiple System Atrophy Treating With Tllsh2910 - a Randomized, Placebo-controlled, Double-blinded, Cross-over, Single-center Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Ataxia, Cerebellar
Multiple System Atrophy
Keywords: multiple system atrophy, cerebellar ataxia, NMDA, microbiota
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2019-04-03
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility 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.

Primary outcomes:
measure: =Scale for the assessment and rating of ataxia (SARA) score
timeFrame: Baseline, 12 weeks, 24 weeks, 36 weeks
Secondary outcomes:
measure: International Cooperative Ataxia Rating Scale (ICARS) score
timeFrame: Baseline, 12 weeks, 24 weeks, 36 weeks
measure: Unified multiple system atrophy rating scale (UMSARS) Part II score
timeFrame: Baseline, 12 weeks, 24 weeks, 36 weeks
measure: The composition change of gut microbiota
timeFrame: Baseline, 12 weeks
measure: The change of total time needed for a 8-meter walking test
timeFrame: Baseline, 12 weeks, 24 weeks, 36 weeks
measure: The change of the World Health Organization Quality of Life (WHOQOL-BREF) scale
timeFrame: Baseline, 12 weeks, 24 weeks, 36 weeks
measure: The total time needed for 9 hole peg test
timeFrame: Baseline, 12 weeks, 24 weeks, 36 weeks
Other outcomes:
Locations:
city: Taipei city
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital (NTUH)
name: Chun-Hwei Tai
role: PRINCIPAL_INVESTIGATOR
References: