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

NCT03901638 | Terminated Phase 3

• 1 other identifier: 201810015MINC
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Ataxia, Cerebellar; Multiple System Atrophy

Keywords

multiple system atrophy, cerebellar ataxia, NMDA, microbiota

Outcome Measures

Primary Outcomes (1)

• =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.

  Baseline, 12 weeks, 24 weeks, 36 weeks

Secondary Outcomes (6)

• International Cooperative Ataxia Rating Scale (ICARS) score

  Baseline, 12 weeks, 24 weeks, 36 weeks

• Unified multiple system atrophy rating scale (UMSARS) Part II score

  Baseline, 12 weeks, 24 weeks, 36 weeks

• The composition change of gut microbiota

  Baseline, 12 weeks

• The change of total time needed for a 8-meter walking test

  Baseline, 12 weeks, 24 weeks, 36 weeks

• The change of the World Health Organization Quality of Life (WHOQOL-BREF) scale

  Baseline, 12 weeks, 24 weeks, 36 weeks

Study Arms (2)

Tllsh2910 to placebo

EXPERIMENTAL

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

Drug: Tllsh2910; Drug: Placebo

Placebo to Tllsh2910

EXPERIMENTAL

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

Drug: Tllsh2910; Drug: Placebo

Interventions

Tllsh2910 DRUG

Tllsh2910 80mg twice per day orally for 12 weeks

Placebo to Tllsh2910; Tllsh2910 to placebo

Placebo DRUG

Placebo

Placebo to Tllsh2910; Tllsh2910 to placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Clinically confirmed cerebellar ataxia with a SARA total score ≥ 3 (range 0-40).
• \. Clinical diagnosis of probable or possible MSA-C.
• \. Patients older than 18 years old and younger than 80 years old.

You may not qualify if:

• \. Major systemic diseases such as hepatic, renal or heart failure, malignancy, stroke.
• \. Concomitant medication which inhibit CYP2C19 enzyme such as Clopidogrel, cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, fluoxetine, fluvoxamine, ticlopidine.
• \. Pregnancy and/or breastfeeding.
• \. Acute diseases that might interfere with the trial.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

MeSH Terms

Conditions

Cerebellar Ataxia; Multiple System Atrophy

Condition Hierarchy (Ancestors)

Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Primary Dysautonomias; Autonomic Nervous System Diseases; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Chun-Hwei Tai

  National Taiwan University Hospital (NTUH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2019
• First Posted: April 3, 2019
• Study Start: April 2, 2019
• Primary Completion: April 3, 2023
• Study Completion: April 3, 2023
• Last Updated: April 7, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)