Deep Brain Stimulation for Tourette Syndrome

Overseen By Emily Rafferty, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Must be taking: Dopamine blockers, Alpha-2 agonists

Must not be taking: Stimulants, Anticonvulsants

Disqualifiers: Previous neurosurgery, Untreated anxiety, Severe comorbidity, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

8 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial involves using a small implantable device to help control severe tics in patients with Tourette syndrome. The device works by monitoring brain activity and sending electrical signals to specific brain areas to stop the tics. This method has been increasingly used for symptom management in severe cases of Tourette syndrome.

Do I have to stop taking my current medications for the trial?

The trial requires that you keep your Tourette Syndrome medications stable and unchanged throughout the study. If you have stopped taking TS medications, you must be stabilized for three months off them before participating.

What data supports the effectiveness of the treatment Medtronic Percept Neurostimulator for Tourette Syndrome?

Research shows that deep brain stimulation (DBS) can significantly reduce tic severity in patients with severe Tourette Syndrome who do not respond to other treatments. In one study, patients experienced a 37% improvement in tic severity after DBS, and this effect was sustained with a 49% improvement one year after surgery. ^{1 2 3 4 5}

Is deep brain stimulation generally safe for humans?

Deep brain stimulation (DBS) has been used safely for various conditions like Parkinson's disease and obsessive-compulsive disorder. In studies for Tourette syndrome, some patients experienced side effects like speech difficulties and infections, but these were generally manageable. Overall, DBS is considered a safe treatment option, though it carries some surgical risks. ^{3 4 6 7 8}

How is the Medtronic Percept Neurostimulator treatment different from other treatments for Tourette Syndrome?

The Medtronic Percept Neurostimulator is a deep brain stimulation (DBS) device that targets specific brain areas to reduce tics in patients with severe Tourette Syndrome who do not respond to other treatments. Unlike medications, which can have systemic side effects, DBS offers a targeted approach, although it requires surgery and carries risks like infection or bleeding. ^{1 4 9 10 11}

Research Team

Michael Okun, MD

Principal Investigator

University of Florida

Christopher Butson, PhD

Principal Investigator

University of Florida

Aysegul Gunduz, PhD

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for adults with severe Tourette Syndrome (TS) that's not improved with medication. They must have a confirmed diagnosis by specialists, stable mental health if they have depression, and a significant impact on their life due to TS. Pregnant women or those planning pregnancy during the study are excluded, as well as individuals with drug-induced tics, recent suicide attempts or substance abuse, metal in the head, previous brain surgery, or other serious health issues.

Inclusion Criteria

I have been diagnosed with Tourette Syndrome by both a specialized neurologist and a psychiatrist.

I am 18 years old or older.

Must be willing to keep TS related medications stable and unchanged throughout the trial.

Exclusion Criteria

I haven't attempted suicide, abused substances, or had multiple failed medication treatments in the last six months.

I experience severe mental health issues or only have simple body movements.

I have not had brain surgery, metal implants in my head, or any type of implanted stimulator.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation and Monitoring

Participants are implanted with the Medtronic Percept PC device and monitored for tic detection and suppression

6 months

Regular in-person visits for monitoring and adjustments

Follow-up

Participants are monitored for safety and effectiveness after the implantation and monitoring phase

4 weeks

Treatment Details

Interventions

• Medtronic Percept Neurostimulator

Trial Overview The trial tests an FDA-approved device called 'Medtronic Percept PC', which is implanted into the brain to detect and suppress tic symptoms in TS patients. It targets specific areas of the brain and records neural signals to understand how tics occur and can be controlled.

Participant Groups

Group I: Medtronic Percept Neurostimulator Experimental Treatment 1 Intervention

This is a deep brain stimulator that can also record brain signals and deliver stimulation through a control algorithm based on brain activity.

Medtronic Percept Neurostimulator is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Medtronic Percept PC for:

• Parkinson's disease
• essential tremor
• dystonia
• epilepsy
• obsessive-compulsive disorder

Approved in European Union as Medtronic Percept PC for:

• Parkinson's disease
• essential tremor
• dystonia
• epilepsy
• obsessive-compulsive disorder

Approved in Japan as Medtronic Percept RC for:

• Parkinson's disease
• essential tremor
• dystonia
• epilepsy

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

Deep brain stimulation (DBS) has shown promising results in reducing tics and improving comorbidities in patients with severe, refractory Tourette's syndrome, particularly in younger adults who experience significant social impairment.

The effectiveness of DBS may depend on the specific target area in the brain, highlighting the need for careful patient selection and target choice, as well as the importance of a skilled multidisciplinary team for managing the complexities of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Issues related to deep brain stimulation for treatment-refractory Tourette's syndrome. Porta, M., Servello, D., Sassi, M., et al.[2010]

In a study of 6 patients with treatment-refractory Tourette's syndrome who underwent GPi-deep brain stimulation (DBS), 4 patients showed significant functional improvement, as measured by the Global Assessment of Functioning Scale (GAF), with scores increasing from an average of 53.75 to 83.75 over a follow-up period of 12 to 72 months.

The study highlights the importance of assessing psychosocial outcomes alongside tic severity, as improvements in tic symptoms were correlated with enhanced quality of life, indicating that successful DBS treatment can lead to significant psychosocial changes that both patients and clinicians should be aware of.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional outcome and quality of life in Tourette's syndrome after deep brain stimulation of the posteroventrolateral globus pallidus internus: long-term follow-up. Dehning, S., Leitner, B., Schennach, R., et al.[2014]

Bilateral deep brain stimulation of the centromedian parafascicular complex (CM-Pf) in an adolescent with treatment-resistant Tourette's syndrome led to positive outcomes, including improved adaptive functioning and reduced need for psychiatric medications over 1.5 years.

Neurocognitive testing showed no significant changes, and importantly, the patient reported no suicidal thoughts after the procedure, suggesting that deep brain stimulation can be a safe and effective intervention for severe cases of Tourette's syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychiatric Outcome of an Adolescent Who Received Deep Brain Stimulation for Tourette's Syndrome. Pullen, SJ., Wall, CA., Lee, KH., et al.[2022]

Deep brain stimulation of the thalamus significantly reduced tic severity in patients with refractory Tourette syndrome, showing a 37% improvement during stimulation and a sustained 49% improvement one year post-surgery, as measured by the Yale Global Tic Severity Scale.

While the stimulation was effective in reducing tics, there were notable adverse effects, including cognitive challenges in attention and energy levels, as well as serious events like a small hemorrhage and infection, highlighting the need for careful consideration of risks in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind clinical trial of thalamic stimulation in patients with Tourette syndrome. Ackermans, L., Duits, A., van der Linden, C., et al.[2022]

In a long-term follow-up of 5-6 years involving 18 patients with severe Tourette Syndrome, bilateral thalamic deep brain stimulation (DBS) resulted in a significant reduction in tic severity and improvements in obsessive-compulsive behaviors, anxiety, and depressive symptoms, indicating its efficacy as a treatment.

Despite the positive outcomes, there were challenges such as non-compliance and differing satisfaction levels between patients and medical teams, suggesting the need for better patient selection and controlled studies for future DBS interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for treatment of refractory Tourette syndrome: long-term follow-up. Porta, M., Servello, D., Zanaboni, C., et al.[2012]

Deep brain stimulation is recognized as a safe and effective treatment for several neurological disorders, including Parkinson's disease, dystonia, tremor, and obsessive-compulsive disorder, with FDA approval for these uses.

Research is expanding into the use of deep brain stimulation for other neuropsychiatric conditions like dementia, depression, and epilepsy, with new targets being explored to enhance treatment for symptoms that do not respond well to traditional medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances and Future Directions of Neuromodulation in Neurologic Disorders. Burns, MR., Chiu, SY., Patel, B., et al.[2021]

Bilateral deep brain stimulation (DBS) of the thalamic CM-Pf complex significantly reduced tic severity in 10 patients with severe, treatment-resistant Tourette syndrome, with an average improvement of 54% over a follow-up period of about 26 months.

The procedure was found to be safe, with no intraoperative complications and manageable postoperative issues, supporting the use of CM-Pf DBS as an effective treatment option for patients with refractory Tourette syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Centromedian-Parafascicular Complex Deep Brain Stimulation for Tourette Syndrome: A Retrospective Study. Testini, P., Zhao, CZ., Stead, M., et al.[2018]

Deep brain stimulation (DBS) significantly reduced tic severity in 25 Japanese patients with refractory Tourette syndrome, showing an average decrease of 45.2% at 1 year and 56.6% at the last follow-up after 3 years, which aligns with international efficacy reports.

While DBS is effective, it carries risks such as dysarthria (32% of patients) and device infection (12%), highlighting the need for careful patient selection and consideration of surgical risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Refractory Tourette Syndrome: Electrode Position and Clinical Outcome. Kimura, Y., Iijima, K., Takayama, Y., et al.[2021]

Bilateral thalamic deep brain stimulation can lead to significant and sustained tic reduction in Tourette Syndrome patients, with one patient maintaining a 92.6% improvement in tics after 10 years.

While tic reduction was sustained, attention to psychosocial adaptation is crucial, as one patient experienced cognitive decline and increased aggression, highlighting the need for comprehensive post-surgery support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of thalamic deep brain stimulation in two patients with Tourette syndrome. Ackermans, L., Duits, A., Temel, Y., et al.[2022]

Deep brain stimulation (DBS) has shown significant clinical improvement in managing tics for individuals with Tourette syndrome, particularly targeting the centromedian thalamus and globus pallidus internus.

Despite the promising results, the current evidence is limited due to small patient numbers and varying study methodologies, prompting the creation of an international registry to standardize data collection and enhance research collaboration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Tourette Syndrome: Potential Role in the Pediatric Population. Deeb, W., Malaty, I.[2021]

Thalamic deep brain stimulation (DBS) showed significant long-term tic reduction in some patients with Tourette syndrome, with one patient experiencing an 88.9% improvement over 78 months, indicating potential for sustained efficacy.

However, the long-term follow-up revealed increasing side effects, such as reduced energy and visual disturbances, leading some patients to switch off the stimulator or require additional surgeries to change the stimulation target.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thalamic Deep Brain Stimulation for Refractory Tourette Syndrome: Clinical Evidence for Increasing Disbalance of Therapeutic Effects and Side Effects at Long-Term Follow-Up. Smeets, AYJM., Duits, AA., Leentjens, AFG., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Issues related to deep brain stimulation for treatment-refractory Tourette's syndrome. [2010]

2. England pubmed.ncbi.nlm.nih.gov

Functional outcome and quality of life in Tourette's syndrome after deep brain stimulation of the posteroventrolateral globus pallidus internus: long-term follow-up. [2014]

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

Neuropsychiatric Outcome of an Adolescent Who Received Deep Brain Stimulation for Tourette's Syndrome. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Double-blind clinical trial of thalamic stimulation in patients with Tourette syndrome. [2022]

5. Austria pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for treatment of refractory Tourette syndrome: long-term follow-up. [2012]

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

Advances and Future Directions of Neuromodulation in Neurologic Disorders. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Centromedian-Parafascicular Complex Deep Brain Stimulation for Tourette Syndrome: A Retrospective Study. [2018]

8. Japan pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Refractory Tourette Syndrome: Electrode Position and Clinical Outcome. [2021]

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

Long-term outcome of thalamic deep brain stimulation in two patients with Tourette syndrome. [2022]

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

Deep Brain Stimulation for Tourette Syndrome: Potential Role in the Pediatric Population. [2021]

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

Thalamic Deep Brain Stimulation for Refractory Tourette Syndrome: Clinical Evidence for Increasing Disbalance of Therapeutic Effects and Side Effects at Long-Term Follow-Up. [2022]