Ataxia, CerebellarPhase 3NCT03901638
Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy
A Phase 3 study testing Tllsh2910 in people with Ataxia, Cerebellar and Multiple System Atrophy, run by National Taiwan University Hospital at 1 site in Taiwan.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Ataxia, Cerebellar, Multiple System Atrophy
- What is being tested?
- Tllsh2910
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteTaiwan
- Study dates
- 2 Apr 2019to 3 Apr 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Ataxia, Cerebellar, Multiple System Atrophy
- Being tested
- Tllsh2910, Placebo
- Keywords
- multiple system atrophy, cerebellar ataxia, NMDA, microbiota
- Medical subject headings
- Cerebellar Ataxia, Multiple System Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tllsh2910Drug
Tllsh2910 80mg twice per day orally for 12 weeks
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Tllsh2910 to placebo | Experimental | Tllsh2910 160mg per day for 12 weeks with wash-out period 12 weeks and subsequent placebos for 12 weeks. Receives: 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 Receives: Drug: Tllsh2910; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
=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.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks
Secondary outcomes (6)
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.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks
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.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks
The composition change of gut microbiota
The gut microbiota will be measured at baseline and 12th weeks.
Measured: Baseline, 12 weeks
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.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks
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.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks
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.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2019
- Study start2 Apr 2019
- Primary completion3 Apr 2023
- Study completion3 Apr 2023
Why it stopped: Project replanning
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ataxia, CerebellarStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chun-Hwei Tai, Principal investigator, National Taiwan University Hospital (NTUH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03901638
- Sponsor's protocol ID
- 201810015MINC
- Status last verified
- Apr 2020
- First submitted
- 24 Mar 2019
- Last updated
- 7 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03901638
- Acronym / sponsor ID
- 201810015MINC
- Conditions
- Ataxia, Cerebellar, Multiple System Atrophy
- Keywords
- multiple system atrophy, cerebellar ataxia, NMDA, microbiota
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Project replanning
- Enrolment
- 18 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 2 Apr 2019 (actual)
- Primary completion
- 3 Apr 2023 (actual)
- Study completion
- 3 Apr 2023 (actual)
- First posted
- 3 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tllsh2910 to placebo | Experimental | Drug: Tllsh2910, Drug: PlaceboTllsh2910 160mg per day for 12 weeks with wash-out period 12 weeks and subsequent placebos for 12 weeks. |
| Placebo to Tllsh2910 | Experimental | Drug: Tllsh2910, Drug: PlaceboPlacebos for 12 weeks with wash-out period 12 weeks and subsequent Tllsh2910 160mg per day for 12 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tllsh2910Tllsh2910 80mg twice per day orally for 12 weeks | Drug | Placebo to Tllsh2910, Tllsh2910 to placebo |
| PlaceboPlacebo | Drug | Placebo to Tllsh2910, Tllsh2910 to placebo |
Primary outcome
=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.
6 secondary outcomes
International Cooperative Ataxia Rating Scale (ICARS) score
Time frame: Baseline, 12 weeks, 24 weeks, 36 weeks
Unified multiple system atrophy rating scale (UMSARS) Part II score
Time frame: Baseline, 12 weeks, 24 weeks, 36 weeks
The composition change of gut microbiota
Time frame: Baseline, 12 weeks
The change of total time needed for a 8-meter walking test
Time frame: Baseline, 12 weeks, 24 weeks, 36 weeks
The change of the World Health Organization Quality of Life (WHOQOL-BREF) scale
Time frame: Baseline, 12 weeks, 24 weeks, 36 weeks
The total time needed for 9 hole peg test
Time frame: Baseline, 12 weeks, 24 weeks, 36 weeks
Results and safety
The study was stopped early (reason given: Project replanning). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chun-Hwei Tai principal investigator
National Taiwan University Hospital (NTUH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tllsh2910 in people with Ataxia, Cerebellar and Multiple System Atrophy, run by National Taiwan University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Project replanning). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
=Scale for the assessment and rating of ataxia (SARA) score (time frame: Baseline, 12 weeks, 24 weeks, 36 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2023.