Speech-motor behavioral testing

Recruiting at 2 trial locations

Overseen By Anne Findlay

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must not be taking: Certain medications

Disqualifiers: Neurological, Psychiatric, Alcohol, Drug, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

660 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will investigate the how the cerebellum is involved in speech motor learning over time and short-term corrections in patients with cerebellar ataxia and healthy controls. This will be accomplished through three approaches: behavioral studies, magnetic resonance imaging (MRI), and transcranial magnetic stimulation (TMS). During behavioral studies, participants will be asked to speak into a microphone while their voice is played back over earphones, and to do other speaking tasks. MRI will be acquired to perform a detailed analysis on brain function and anatomy related to speech and the cerebellum. In healthy controls, TMS will also be performed to temporarily disrupt the cerebellum before, during, or after the participant performs speaking tasks. Patients with cerebellar ataxia and healthy volunteers will be asked to complete behavioral studies and/or MRI; healthy volunteers may be asked to additionally participate in TMS.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are a healthy volunteer, certain medications might be a concern for TMS participation. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of this treatment for cerebellar ataxia?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can improve symptoms of cerebellar ataxia, such as balance and coordination, as seen in studies where patients experienced better scores on ataxia rating scales after treatment. Additionally, a systematic review and meta-analysis found that rTMS over the cerebellum significantly improved ataxia symptoms without causing significant adverse effects. ^{1 2 3 4 5}

Is TMS and MRI safe for treating cerebellar ataxia?

Repetitive Transcranial Magnetic Stimulation (rTMS) has been studied for various neurological conditions, including cerebellar ataxia, and is generally considered safe with only mild side effects reported in some cases. There is a slight risk of seizures, but no severe adverse events have been commonly reported in studies. ^{4 6 7 8 9}

How does the TMS and MRI treatment for cerebellar ataxia differ from other treatments?

The TMS and MRI treatment for cerebellar ataxia is unique because it uses non-invasive brain stimulation (TMS) to improve brain function, which is not a standard treatment for this condition. TMS has shown promise in improving symptoms in other neurological disorders by enhancing brain connectivity and function, offering a novel approach compared to traditional therapies. ^{5 8 9 10 11}

Research Team

Ben Parrell, Ph.D.

Principal Investigator

University of Wisconsin, Madison

Richard Ivry, Ph.D.

Principal Investigator

University of California, Berkeley

John F. Houde, Ph.D.

Principal Investigator

University of California, San Francisco

Srikantan S. Nagarajan, Ph.D.

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for people with cerebellar ataxia who have normal hearing and speak American English, or healthy individuals without physical/neurological issues. Participants must not have seizures, metal implants, heart disease, be pregnant, use hearing aids, or suffer from psychiatric illnesses unrelated to cerebellar damage.

Inclusion Criteria

For some studies, primary language of American English may be required

You have a condition called cerebellar ataxia that affects your balance and coordination and you have no hearing problems, OR you are a healthy person with no history of physical or neurological problems and have normal speech, hearing, and reading abilities.

Exclusion Criteria

Ongoing seizures that are not well controlled despite medication

Any contraindications to participating in a TMS study including the following: epilepsy, use of certain medications, heart disease, and pregnancy; scalp wounds or infections; any other contraindication discovered during screening procedures

Any condition that would prevent the subject from giving voluntary informed consent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Behavioral Studies

Participants perform speaking tasks while their voice is played back over earphones, and other speaking tasks are conducted.

4-6 weeks

Multiple visits (in-person)

MRI Studies

MRI is acquired to analyze brain function and anatomy related to speech and the cerebellum.

1-2 weeks

1-2 visits (in-person)

TMS Studies

In healthy controls, TMS is performed to temporarily disrupt the cerebellum during speaking tasks.

1-2 weeks

1-2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the main study activities.

4 weeks

Treatment Details

Interventions

• MRI
• Speech-motor behavioral testing
• TMS

Trial Overview The study examines the cerebellum's role in speech by using behavioral tests where participants talk into a mic with voice feedback. MRI scans analyze brain function and anatomy related to speech. In healthy subjects only, TMS disrupts cerebellum activity during speaking tasks.

Participant Groups

Group I: Patients with cerebellar ataxia (CA) Experimental Treatment 2 Interventions

Behavioral testing including various speaking tasks Magnetic resonance imaging (MRI)

Group II: Additional healthy volunteers Experimental Treatment 3 Interventions

Behavioral testing including various speaking tasks Magnetic resonance imaging (MRI) Transcranial magnetic stimulation (TMS)

Group III: Matched controls Active Control 2 Interventions

Behavioral testing including various speaking tasks Magnetic resonance imaging (MRI)

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

University of Wisconsin, Madison

Collaborator

Trials

1,249

Recruited

3,255,000+

National Institute on Deafness and Other Communication Disorders (NIDCD)

Collaborator

Trials

377

Recruited

190,000+

University of California, Berkeley

Collaborator

Trials

193

Recruited

716,000+

Findings from Research

A review of 84 single pulse and paired-pulse TMS studies with 1091 Parkinson's disease patients, and 77 repetitive TMS studies with 1137 patients, found a very low risk of adverse events, with no seizures reported.

The overall risk of adverse events from rTMS was 0.040 per patient, with common side effects being mild and transient, such as headaches and scalp pain, indicating that TMS is generally safe for Parkinson's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial magnetic stimulation in Parkinson's disease: a review of the literature. Vonloh, M., Chen, R., Kluger, B.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effectiveness of High-Frequency Repetitive Transcranial Magnetic Stimulation in Patients With Spinocerebellar Ataxia Type 3. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Cerebellar TMS in treatment of a patient with cerebellar ataxia: evidence from clinical, biomechanics and neurophysiological assessments. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation of the cerebellum improves ataxia and cerebello-fronto plasticity in multiple system atrophy: a randomized, double-blind, sham-controlled and TMS-EEG study. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Repetitive Transcranial Magnetic Stimulation in Cerebellar Ataxia: a Systematic Review and Meta-analysis. [2023]

5. Denmark pubmed.ncbi.nlm.nih.gov

Reduced intracortical facilitation in patients with cerebellar degeneration. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Safety of transcranial magnetic stimulation in Parkinson's disease: a review of the literature. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

The Effect of Cerebellar rTMS on Modulating Motor Dysfunction in Neurological Disorders: a Systematic Review. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Short-term efficacy of repetitive transcranial magnetic stimulation in SCA3: A prospective, randomized, double-blind, sham-controlled study. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Improvement of hand dexterity following motor cortex rTMS in multiple sclerosis patients with cerebellar impairment. [2008]

10. Italy pubmed.ncbi.nlm.nih.gov

Motor cortex rTMS improves dexterity in relapsing-remitting and secondary progressive multiple sclerosis. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical diagnostic utility of transcranial magnetic stimulation in neurological disorders. Updated report of an IFCN committee. [2023]