Cerebellar AtaxiaNCT05351255
Motor Learning After Cerebellar Damage: The Role of the Primary Motor Cortex
A study testing Transcranial Magnetic Stimulation (TMS) in people with Cerebellar Ataxia, run by Albert Einstein Healthcare Network at 1 site in United States.
Trial summary
This study will determine (1) whether baseline inhibitory activity in the primary motor cortex can predict motor learning ability in individuals with cerebellar degeneration, and (2) whether modulating primary motor cortex activity with non-invasive brain stimulation alters motor learning ability in this population. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cerebellar Ataxia
- What is being tested?
- Transcranial Magnetic Stimulation (TMS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2022to 19 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Diagnosis of cerebellar ataxia from cerebellar degeneration
- Normal or corrected-to-normal vision
- Normal or corrected-to-normal hearing
- Meet safety criteria for receipt of transcranial magnetic stimulation
Who cannot join
- Extrapyramidal signs on neurologic examination
- History of alcohol or illicit drug abuse
- Peripheral sensory loss in the arms
- Cognitive or attention deficits that interfere with testing, the capacity to understand and follow task instructions, or the capacity to provide informed consent
- Orthopedic injury or pain in the arms
Trial locations and contacts
1 site in 1 country.
United States1 site
Moss Rehabilitation Research Institute
Elkins Park, Pennsylvania, 19027
About this study
This study will determine (1) whether baseline inhibitory activity in the primary motor cortex can predict motor learning ability in individuals with cerebellar degeneration, and (2) whether modulating primary motor cortex activity with non-invasive brain stimulation alters motor learning ability in this population.
Read the detailed description
Cerebellar damage causes the disabling movement disorder ataxia, which is characterized by impaired movement coordination affecting all body movements. In the arms, ataxia causes reaching movements with irregular, oscillating, and prolonged trajectory paths. People with cerebellar ataxia (PWCA) are also impaired in an important form of motor learning, called adaptation, which normally keeps movement well calibrated. In prior research, the principal investigator showed that PWCA can learn to correct their reaching movements if they instead employ reinforcement learning (RL). Although many PWCA learned optimally in RL conditions, this prior work found variability across individuals: some learned more than others. While adaptation critically relies on cerebellar integrity, RL depends more heavily on dopaminergic circuitry in the midbrain and excitatory plasticity in M1. Cerebellar damage has been shown to increase intracortical inhibition in M1, which may hamper the plasticity needed for RL. The repetitive TMS protocols of continuous theta burst stimulation (cTBS) and intermittent theta burst stimulation (iTBS) have further been shown to modulate intracortical inhibition: cTBS decreases it, while iTBS increases it. Here, the investigators will systematically test whether increased intracortical inhibition in M1 predicts RL capacity (Aim 1) and whether modulating inhibition in M1 can alter RL capacity in PWCA (Aim 2). 12 PWCA from a degenerative condition will complete 4 experimental sessions over a 6-month period. In session 1, TMS will be used to assess baseline recruitment curves for corticomotor excitability and short-interval intracortical inhibition, and the cortical silent period. PWCA will then complete a standardized clinical rating of their ataxia severity and an established behavioral task that requires learning a reaching skill using the RL paradigm. In sessions 2-4, PWCA will complete 3 additional sessions of the RL task. In each session, PWCA will receive cTBS, iTBS, or sham stimulation to modulate intracortical inhibition in M1 prior to performing the RL task. For Aim 1, the investigators will use multi-level regression to quantify relationships between TMS measures of M1 state and the magnitude and speed of learning in the RL task. For Aim 2, the investigators will use multi-level modeling to quantify differences in the magnitude and speed of learning across stimulation conditions. The investigators hypothesize that increased baseline inhibition in M1 will show a positive association with a lower magnitude and speed of learning in the RL task (Aim 1), and cTBS will improve the magnitude of learning, the speed of learning, or both, in the RL task relative to iTBS or sham stimulation (Aim 2).
- Conditions
- Cerebellar Ataxia
- Being tested
- Transcranial Magnetic Stimulation (TMS)
- Medical subject headings
- Cerebellar Ataxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic Stimulation (TMS)Device
Aim 2 of the study includes an intervention where participants receive a repetitive TMS protocol called theta burst stimulation (TBS) to study its effect on motor learning behavior.
| Study group | Role | What they receive |
|---|---|---|
| rTMS Intervention | Experimental | In aim 2 of the study, participants receive a repetitive transcranial magnetic stimulation intervention called theta burst stimulation (TBS) to study its effect on motor learning behavior. All participants will complete 3 sessions in which they will receive continuous TBS, intermittent TBS, or sham TBS before completing a behavioral motor learning task. The order of TBS sessions will be counter-balanced across participants. Receives: Device: Transcranial Magnetic Stimulation (TMS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
International Cooperative Ataxia Rating Scale Total Score
The sore out of 100 that results from assessment using the International Cooperative Ataxia Rating Scale (ICARS). The rating scale has a minimum score of 0 and a maximum score of 100. Higher scores indicate more severe impairment.
Measured: Baseline
International Cooperative Ataxia Rating Scale Limb Coordination Sub-Score
The score out of 52 that results from assessment using the Limb Kinetic sub-section of the International Cooperative Ataxia Rating Scale (ICARS). The Limb Kinetic sub-score has a minimum score of 0 and a maximum score of 52. Higher scores indicate more severe impairment.
Measured: Baseline
Reinforcement Learning Rate
The slope of the time series of reach path lengths (determined from digital 3D kinematic data recorded using a motion capture system) over the first 80 trials of the intervention phase of the reinforcement motor learning task.
Measured: During the intervention, assessed up to 10 days
Total Reinforcement Learning
The difference in mean reach path length (determined from digital 3D kinematic data recorded using a motion capture system) between the baseline phase and the end of the intervention phase of the reinforcement motor learning task.
Measured: During the intervention, assessed up to 10 days
Slope of the Corticomotor Excitability Recruitment Curve
The slope of motor evoked potential amplitudes (determined from electromyographic recordings of target muscle activity) between TMS intensities of 120-140% of resting motor threshold.
Measured: Baseline
Slope of the Short-Interval Intracortical Inhibition (SICI) Recruitment Curve
SICI will be computed as the difference in average motor evoked potential amplitude (determined from electromyographic recordings of target muscle activity) between a TMS condition where a single conditioning pulse is applied 3 ms before a single test pulse and a TMS condition where only the test pulse is applied. A range of conditioning pulse TMS intensities will be tested and SICI will be measured for each. The outcome measure comprises the slope of the SICI values over each conditioning pulse intensity.
Measured: Baseline
Cortical Silent Period
Single pulses of TMS will be applied at an intensity of 110% of resting motor threshold while participants tonically activate the target muscle at 20% of their maximum voluntary isometric contraction. 12 repetitions of the protocol will be performed. The outcome measure comprises the average time, in ms, from the end of the motor evoked potential to the reoccurrence of tonic background electromyographic activity.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2022
- Study start1 Jul 2022
- Primary completion19 Dec 2026 (estimated)
- Study completion19 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebellar AtaxiaStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Albert Einstein Healthcare Network
- Sponsor type
- University, hospital or other
- Collaborators
- Medical University of South Carolina
- Responsible party
- Principal investigator, Amanda Therrien, PhD, Albert Einstein Healthcare Network
- Investigators
- Amanda S Therrien, PhD, Principal investigator, Moss Rehabilitation Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05351255
- Sponsor's protocol ID
- AEHN-IRB-2022-881
- Other IDs
- P2CHD086844
- Status last verified
- Jan 2025
- First submitted
- 6 Apr 2022
- Last updated
- 15 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Participants will indicate, via written informed consent, whether they allow the study team to share the data collected as part of this study with other researchers. all individual participant data (IDP) that underlie results in a publication will be made available to other researchers. The study team will maintain the confidentiality of participant information to the extent possible. That is, participant's names and other identifying information will be removed from the data prior to sharing. The data will be coded with the participant's arbitrary study identification code. The key linking study identification codes to participant's identity will only be accessible to approved members of the study team.
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Motor Learning After Cerebellar Damage: The Role of the Primary Motor Cortex
- ClinicalTrials.gov ID
- NCT05351255
- Acronym / sponsor ID
- AEHN-IRB-2022-881
- Conditions
- Cerebellar Ataxia
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Albert Einstein Healthcare NetworkUniversity, hospital or other
- Collaborators
- Medical University of South Carolina
- Study start
- 1 Jul 2022 (actual)
- Primary completion
- 19 Dec 2026 (estimated)
- Study completion
- 19 Dec 2026 (estimated)
- First posted
- 28 Apr 2022 (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.
This study will determine (1) whether baseline inhibitory activity in the primary motor cortex can predict motor learning ability in individuals with cerebellar degeneration, and (2) whether modulating primary motor cortex activity with non-invasive brain stimulation alters motor learning ability in this population.
Detailed description
Cerebellar damage causes the disabling movement disorder ataxia, which is characterized by impaired movement coordination affecting all body movements. In the arms, ataxia causes reaching movements with irregular, oscillating, and prolonged trajectory paths. People with cerebellar ataxia (PWCA) are also impaired in an important form of motor learning, called adaptation, which normally keeps movement well calibrated. In prior research, the principal investigator showed that PWCA can learn to correct their reaching movements if they instead employ reinforcement learning (RL). Although many PWCA learned optimally in RL conditions, this prior work found variability across individuals: some learned more than others. While adaptation critically relies on cerebellar integrity, RL depends more heavily on dopaminergic circuitry in the midbrain and excitatory plasticity in M1. Cerebellar damage has been shown to increase intracortical inhibition in M1, which may hamper the plasticity needed for RL. The repetitive TMS protocols of continuous theta burst stimulation (cTBS) and intermittent theta burst stimulation (iTBS) have further been shown to modulate intracortical inhibition: cTBS decreases it, while iTBS increases it. Here, the investigators will systematically test whether increased intracortical inhibition in M1 predicts RL capacity (Aim 1) and whether modulating inhibition in M1 can alter RL capacity in PWCA (Aim 2). 12 PWCA from a degenerative condition will complete 4 experimental sessions over a 6-month period. In session 1, TMS will be used to assess baseline recruitment curves for corticomotor excitability and short-interval intracortical inhibition, and the cortical silent period. PWCA will then complete a standardized clinical rating of their ataxia severity and an established behavioral task that requires learning a reaching skill using the RL paradigm. In sessions 2-4, PWCA will complete 3 additional sessions of the RL task. In each session, PWCA will receive cTBS, iTBS, or sham stimulation to modulate intracortical inhibition in M1 prior to performing the RL task. For Aim 1, the investigators will use multi-level regression to quantify relationships between TMS measures of M1 state and the magnitude and speed of learning in the RL task. For Aim 2, the investigators will use multi-level modeling to quantify differences in the magnitude and speed of learning across stimulation conditions. The investigators hypothesize that increased baseline inhibition in M1 will show a positive association with a lower magnitude and speed of learning in the RL task (Aim 1), and cTBS will improve the magnitude of learning, the speed of learning, or both, in the RL task relative to iTBS or sham stimulation (Aim 2).
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| rTMS Intervention | Experimental | Device: Transcranial Magnetic Stimulation (TMS)In aim 2 of the study, participants receive a repetitive transcranial magnetic stimulation intervention called theta burst stimulation (TBS) to study its effect on motor learning behavior. All participants will complete 3 sessions in which they will receive continuous TBS, intermittent TBS, or sham TBS before completing a behavioral motor learning task. The order of TBS sessions will be counter-balanced across participants. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of cerebellar ataxia from cerebellar degeneration
- Normal or corrected-to-normal vision
- Normal or corrected-to-normal hearing
- Meet safety criteria for receipt of transcranial magnetic stimulation
Key exclusion criteria (5 listed)
- Extrapyramidal signs on neurologic examination
- History of alcohol or illicit drug abuse
- Peripheral sensory loss in the arms
- Cognitive or attention deficits that interfere with testing, the capacity to understand and follow task instructions, or the capacity to provide informed consent
- Orthopedic injury or pain in the arms
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 |
|---|---|---|
| Transcranial Magnetic Stimulation (TMS)Aim 2 of the study includes an intervention where participants receive a repetitive TMS protocol called theta burst stimulation (TBS) to study its effect on motor learning behavior. | Device | rTMS Intervention |
Primary outcome
International Cooperative Ataxia Rating Scale Total Score
Time frame: Baseline
The sore out of 100 that results from assessment using the International Cooperative Ataxia Rating Scale (ICARS). The rating scale has a minimum score of 0 and a maximum score of 100. Higher scores indicate more severe impairment.
International Cooperative Ataxia Rating Scale Limb Coordination Sub-Score
Time frame: Baseline
The score out of 52 that results from assessment using the Limb Kinetic sub-section of the International Cooperative Ataxia Rating Scale (ICARS). The Limb Kinetic sub-score has a minimum score of 0 and a maximum score of 52. Higher scores indicate more severe impairment.
Reinforcement Learning Rate
Time frame: During the intervention, assessed up to 10 days
The slope of the time series of reach path lengths (determined from digital 3D kinematic data recorded using a motion capture system) over the first 80 trials of the intervention phase of the reinforcement motor learning task.
Total Reinforcement Learning
Time frame: During the intervention, assessed up to 10 days
The difference in mean reach path length (determined from digital 3D kinematic data recorded using a motion capture system) between the baseline phase and the end of the intervention phase of the reinforcement motor learning task.
Slope of the Corticomotor Excitability Recruitment Curve
Time frame: Baseline
The slope of motor evoked potential amplitudes (determined from electromyographic recordings of target muscle activity) between TMS intensities of 120-140% of resting motor threshold.
Slope of the Short-Interval Intracortical Inhibition (SICI) Recruitment Curve
Time frame: Baseline
SICI will be computed as the difference in average motor evoked potential amplitude (determined from electromyographic recordings of target muscle activity) between a TMS condition where a single conditioning pulse is applied 3 ms before a single test pulse and a TMS condition where only the test pulse is applied. A range of conditioning pulse TMS intensities will be tested and SICI will be measured for each. The outcome measure comprises the slope of the SICI values over each conditioning pulse intensity.
Cortical Silent Period
Time frame: Baseline
Single pulses of TMS will be applied at an intensity of 110% of resting motor threshold while participants tonically activate the target muscle at 20% of their maximum voluntary isometric contraction. 12 repetitions of the protocol will be performed. The outcome measure comprises the average time, in ms, from the end of the motor evoked potential to the reoccurrence of tonic background electromyographic activity.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2025.
- Individual participant dataSharing planned: Yes. Participants will indicate, via written informed consent, whether they allow the study team to share the data collected as part of this study with other researchers. all individual participant data (IDP) that underlie results in a publication will be made available to other researchers. The study team will maintain the confidentiality of participant information to the extent possible. That is, participant's names and other identifying information will be removed from the data prior to sharing. The data will be coded with the participant's arbitrary study identification code. The key linking study identification codes to participant's identity will only be accessible to approved members of the study team.
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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.
Amanda S Therrien, PhD principal investigator
Moss Rehabilitation Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation (TMS) in people with Cerebellar Ataxia, run by Albert Einstein Healthcare Network at 1 site in United States.
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 4 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 15 Sep 2025. 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 United States. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
International Cooperative Ataxia Rating Scale Total Score (time frame: Baseline). The study lists 7 primary outcomes in all. 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 15 Sep 2025.