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

Multiple System Atrophy Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03901638
• Other study ID #: 201810015MINC
• Status: Terminated
• Phase: Phase 3
• Start date: April 2, 2019
• Est. completion date: April 3, 2023

Study information

• Verified date: April 2020
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. completion date: April 3, 2023
• Est. primary completion date: April 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Ataxia
• Ataxia, Cerebellar
• Atrophy
• Cerebellar Ataxia
• Multiple System Atrophy
• Shy-Drager Syndrome

Intervention

Drug:
• Tllsh2910
Tllsh2910 80mg twice per day orally for 12 weeks
• Placebo
Placebo

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei city

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	=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	International Cooperative Ataxia Rating Scale (ICARS) score	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.	Baseline, 12 weeks, 24 weeks, 36 weeks
Secondary	Unified multiple system atrophy rating scale (UMSARS) Part II score	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.	Baseline, 12 weeks, 24 weeks, 36 weeks
Secondary	The composition change of gut microbiota	The gut microbiota will be measured at baseline and 12th weeks.	Baseline, 12 weeks
Secondary	The change of total time needed for a 8-meter walking test	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.	Baseline, 12 weeks, 24 weeks, 36 weeks
Secondary	The change of the World Health Organization Quality of Life (WHOQOL-BREF) scale	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.	Baseline, 12 weeks, 24 weeks, 36 weeks
Secondary	The total time needed for 9 hole peg test	The total time needed for 9 hole peg test will be measured at the baseline, 12-week, 24-week, and 36-week.	Baseline, 12 weeks, 24 weeks, 36 weeks