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

National Taiwan University

Status and phase: Terminated; Phase 3

Conditions: Multiple System Atrophy; Ataxia, Cerebellar

Treatments: Drug: Placebo; Drug: Tllsh2910

Study type: Interventional

Funder types: Other

Identifiers

NCT03901638

201810015MINC

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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18 participants in 2 patient groups

Tllsh2910 to placebo

Experimental group

Description:

Tllsh2910 160mg per day for 12 weeks with wash-out period 12 weeks and subsequent placebos for 12 weeks.

Treatment:

Drug: Tllsh2910

Drug: Placebo

Placebo to Tllsh2910

Experimental group

Description:

Placebos for 12 weeks with wash-out period 12 weeks and subsequent Tllsh2910 160mg per day for 12 weeks

Treatment:

Drug: Tllsh2910

Drug: Placebo