Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03901638
Recruitment Status : Recruiting
First Posted : April 3, 2019
Last Update Posted : April 3, 2019
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital

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.

Condition or disease Intervention/treatment Phase
Ataxia, Cerebellar Multiple System Atrophy Drug: Tllsh2910 Drug: Placebo Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : April 2, 2019
Estimated Primary Completion Date : November 15, 2021
Estimated Study Completion Date : November 15, 2021


Arm Intervention/treatment
Experimental: Tllsh2910 to placebo
Tllsh2910 160mg per day for 12 weeks with wash-out period 12 weeks and subsequent placebos for 12 weeks.
Drug: Tllsh2910
Tllsh2910 80mg twice per day orally for 12 weeks

Drug: Placebo
Placebo

Experimental: Placebo to Tllsh2910
Placebos for 12 weeks with wash-out period 12 weeks and subsequent Tllsh2910 160mg per day for 12 weeks
Drug: Tllsh2910
Tllsh2910 80mg twice per day orally for 12 weeks

Drug: Placebo
Placebo




Primary Outcome Measures :
  1. =Scale for the assessment and rating of ataxia (SARA) score [ Time Frame: Baseline, 12 weeks, 24 weeks, 36 weeks ]
    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.


Secondary Outcome Measures :
  1. International Cooperative Ataxia Rating Scale (ICARS) score [ Time Frame: Baseline, 12 weeks, 24 weeks, 36 weeks ]
    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.

  2. Unified multiple system atrophy rating scale (UMSARS) Part II score [ Time Frame: Baseline, 12 weeks, 24 weeks, 36 weeks ]
    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.

  3. The composition change of gut microbiota [ Time Frame: Baseline, 12 weeks ]
    The gut microbiota will be measured at baseline and 12th weeks.

  4. The change of total time needed for a 8-meter walking test [ Time Frame: Baseline, 12 weeks, 24 weeks, 36 weeks ]
    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.

  5. The change of the World Health Organization Quality of Life (WHOQOL-BREF) scale [ Time Frame: Baseline, 12 weeks, 24 weeks, 36 weeks ]
    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.

  6. The total time needed for 9 hole peg test [ Time Frame: Baseline, 12 weeks, 24 weeks, 36 weeks ]
    The total time needed for 9 hole peg test will be measured at the baseline, 12-week, 24-week, and 36-week.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03901638


Contacts
Layout table for location contacts
Contact: Ming-Che Kuo 886-919992342 kuomingche0402@gmail.com
Contact: Shau-Hua Kuo 886-911606669 sarakuo1988@gmail.com

Locations
Layout table for location information
Taiwan
National Taiwan University Hospital Recruiting
Taipei city, Taiwan, 100
Contact: Ming-Che Kuo    886-919992342    kuomingche0402@gmail.com   
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Layout table for investigator information
Principal Investigator: Chun-Hwei Tai National Taiwan University Hospital (NTUH)

Layout table for additonal information
Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT03901638     History of Changes
Other Study ID Numbers: 201810015MINC
First Posted: April 3, 2019    Key Record Dates
Last Update Posted: April 3, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Taiwan University Hospital:
multiple system atrophy, cerebellar ataxia, NMDA, microbiota

Additional relevant MeSH terms:
Layout table for MeSH terms
Ataxia
Cerebellar Ataxia
Atrophy
Multiple System Atrophy
Shy-Drager Syndrome
Pathological Conditions, Anatomical
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Primary Dysautonomias
Autonomic Nervous System Diseases
Basal Ganglia Diseases
Movement Disorders
Neurodegenerative Diseases
Hypotension
Vascular Diseases
Cardiovascular Diseases