rTMS for Impulse Control Disorders in Parkinson's Disease

Recruiting in Morgantown (>99 mi)

Overseen By Mariya V Cherkasova, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: West Virginia University

Must be taking: Dopamine-replacement therapy

Must not be taking: Seizure-threshold reducers

Disqualifiers: Seizures, Brain lesions, Stroke, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1-2 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This study's objective is to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (dlPFC) of patients with Parkinson's Disease (PD) who experience impulse control disorders (ICDs) on impulse control symptoms and cognitive behaviors linked to ICDs: reinforcement learning and delay-discounting. This is a randomized sham-controlled cross-over trial. All patients will undergo a session of active rTMS and a session of sham rTMS, with the order of sessions randomized across participants. Following recruitment and eligibility screening, the eligible participants will undergo two sessions of rTMS (active and sham), immediately followed by neurocognitive tasks and questionnaires, no more than 1-2 weeks apart. Each session will have a duration of approximately 1-1.5 hours.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you must be on dopamine-replacement therapy to participate, and you cannot use substances or medications that significantly reduce seizure threshold.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude people using substances or medications that significantly lower the seizure threshold. It's best to discuss your current medications with the trial team to see if they might be an issue.

What data supports the idea that rTMS for Impulse Control Disorders in Parkinson's Disease is an effective treatment?

The available research shows that repetitive transcranial magnetic stimulation (rTMS) can have positive effects on impulse control disorders in Parkinson's Disease. One study found that rTMS over a specific brain area temporarily reduced a behavior called punding, which is a type of impulse control disorder. This effect was more noticeable when the treatment was applied to the right side of the brain. Another study showed that rTMS could improve movement and reaction times in Parkinson's patients, suggesting it might help with other symptoms too. While rTMS didn't show a big difference compared to a placebo in reducing certain movement problems, it did have some lasting positive effects. Overall, these studies suggest that rTMS might be a helpful treatment for impulse control issues in Parkinson's Disease. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment rTMS for impulse control disorders in Parkinson's disease?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can temporarily reduce punding (a repetitive behavior) in Parkinson's patients without worsening their movement issues. Additionally, rTMS has shown small but significant improvements in dyskinesia (involuntary movements) and enhanced performance in cognitive tasks, suggesting potential benefits for impulse control disorders in Parkinson's disease. ^{1 2 3 4 5}

What safety data exists for rTMS in treating impulse control disorders in Parkinson's Disease?

Safety data for rTMS, including its variants like drTMS, has been extensively reviewed and updated over the years. Initial safety guidelines were established in 1996, with updates in 2008 and 2021, focusing on adverse events, precautions, and dosing considerations. Studies have shown that rTMS can be safely administered to patients with Parkinson's Disease, with some variation in adverse event severity. Specific studies have demonstrated that rTMS can transiently reduce impulse control disorders like punding in Parkinson's Disease without worsening motor symptoms. Overall, rTMS is considered safe when following established guidelines. ^{1 6 7 8 9}

Is rTMS safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) has been used safely in both healthy individuals and those with various brain disorders since the 1990s. While there have been some adverse events like seizures, safety guidelines have been established and updated to minimize risks. Studies show that rTMS, including deep rTMS, can be safely administered to patients with Parkinson's disease and other conditions, with some variation in the rate and severity of side effects. ^{1 6 7 8 9}

Is rTMS a promising treatment for impulse control disorders in Parkinson's disease?

Yes, rTMS is a promising treatment for impulse control disorders in Parkinson's disease. It has shown potential in reducing repetitive behaviors and improving motor performance without worsening symptoms. Studies suggest it could be useful for managing these disorders in Parkinson's patients. ^{1 2 3 10 11}

How does the treatment rTMS differ from other treatments for impulse control disorders in Parkinson's disease?

rTMS (repetitive transcranial magnetic stimulation) is unique because it uses magnetic fields to stimulate specific areas of the brain, like the prefrontal cortex, to help manage impulse control disorders in Parkinson's disease. Unlike medications, it is a non-invasive procedure that can temporarily improve symptoms without worsening motor function. ^{1 2 3 10 11}

Research Team

Mariya V Cherkasova, PhD

Principal Investigator

West Virginia University

Eligibility Criteria

This trial is for Parkinson's Disease patients who struggle with impulse control disorders. Participants will undergo two types of brain stimulation sessions: real and pretend (sham). They must be able to complete tasks and questionnaires after each session, which are spaced 1-2 weeks apart.

Inclusion Criteria

My depression score is 14 or less.

My doctor has diagnosed me with Parkinson's disease.

I am on medication to increase dopamine levels.

Exclusion Criteria

Meeting the criteria for a major psychiatric illness such as schizophrenia or depression (BDI score of 14 or higher)

Pregnancy assessed in female patients

I have a history of seizures or epilepsy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo two sessions of rTMS (active and sham), immediately followed by neurocognitive tasks and questionnaires

1-2 weeks

2 sessions (in-person)

Follow-up

Participants are monitored for changes in impulse control disorder symptoms, reinforcement learning, and delay-discounting

1 hour following each intervention

Treatment Details

Interventions

• rTMS

Trial Overview The study tests if repetitive transcranial magnetic stimulation (rTMS) on a specific brain area can help manage impulse control in Parkinson's patients. It's a cross-over trial where everyone gets both the actual treatment and a fake one at different times.

Participant Groups

Group I: rTMS Active Active Control 1 Intervention

the participant will receive a type of TMS called repetitive TMS (rTMS) wherein the magnetic pulses delivered will be close together in a rapid sequence over the dlPFC. Participants receive excitatory rTMS with a stimulation frequency of 20 Hz between 100-120% of their resting motor threshold.

Group II: rTMS Sham Placebo Group 1 Intervention

Sham rTMS will be the same as real rTMS, except a special sham coil will be used, which produces the same sensation on the scalp of the patients as the real coil but delivers no magnetic stimulation to the brain.

rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder
• Migraines
• Smoking cessation

Approved in European Union as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder

Who Is Running the Clinical Trial?

West Virginia University

Lead Sponsor

Trials

192

Recruited

64,700+

Findings from Research

Low-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex (DLPFC) was found to temporarily reverse punding behavior in four patients with Parkinson's disease, indicating its potential efficacy in treating this impulse-control disorder.

The treatment did not worsen motor impairment in the patients, suggesting that rTMS could be a safe therapeutic option for managing punding and possibly other impulse-control disorders associated with dopamine-replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation transiently reduces punding in Parkinson's disease: a preliminary study. Nardone, R., De Blasi, P., Höller, Y., et al.[2021]

In a study involving 6 patients with Parkinson's disease and 10 normal controls, repetitive transcranial magnetic stimulation (rTMS) significantly improved choice reaction time and movement time in patients without affecting their error rate, suggesting enhanced motor function.

The rTMS treatment also improved performance on a grooved peg-board test in Parkinson's patients, particularly when they were not on medication, indicating its potential as a therapeutic intervention for motor symptoms in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Akinesia in Parkinson's disease. II. Effects of subthreshold repetitive transcranial motor cortex stimulation. Pascual-Leone, A., Valls-Solé, J., Brasil-Neto, JP., et al.[2019]

In a study involving 10 patients with Parkinson's disease, real repetitive transcranial magnetic stimulation (rTMS) showed a small but significant reduction in dyskinesia severity compared to baseline, particularly affecting dystonia symptoms.

Real rTMS resulted in sustained improvements in subjective dyskinesia scores for up to 3 days after treatment, with no reported side effects or adverse impacts on motor function, suggesting its potential as a therapeutic option for managing dyskinesias in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for levodopa-induced dyskinesias in Parkinson's disease. Filipović, SR., Rothwell, JC., van de Warrenburg, BP., et al.[2013]

A single session of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the inferior frontal gyri significantly improved performance on the Stroop test in ten nondemented Parkinson's disease patients, indicating enhanced cognitive processing speed.

While rTMS improved specific aspects of the Stroop test, it did not affect overall scores on the Frontal Assessment Battery, suggesting targeted effects of rTMS on certain cognitive tasks rather than a broad enhancement of executive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of the inferior frontal gyri in cognitive processing of patients with Parkinson's disease: a pilot rTMS study. Srovnalova, H., Marecek, R., Rektorova, I.[2019]

In a study involving 11 patients with Parkinson's disease (PD), subthreshold repetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex did not show a consistent effect on fine motor movement performance, as measured by the Grooved Pegboard test.

While some patients experienced faster performance with rTMS, the overall results indicated no significant therapeutic benefit, suggesting that this method may not be effective for improving movement in PD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous repetitive transcranial magnetic stimulation does not speed fine movement in PD. Ghabra, MB., Hallett, M., Wassermann, EM.[2019]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

Deep repetitive transcranial magnetic stimulation (drTMS) is safe for patients with various Parkinson Syndromes and can effectively reduce their self-reported motor symptom severity and depression, based on a retrospective analysis of 21 patients.

The treatment showed more significant benefits in older patients with Parkinson's disease, although it did not demonstrate any improvement in cognitive performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Deep Repetitive Transcranial Magnetic Stimulation (drTMS) against Medical Refractory Symptoms in Parkinson Syndromes: First German Real-World Data with a Specific H5 Coil. Cont, C., Lehto, A., Stute, N., et al.[2022]

In a study involving 26 patients with mild to moderate Parkinson's disease, 50-Hz repetitive transcranial magnetic stimulation (rTMS) was found to be safe, with no adverse effects or increased risk of cortical excitability.

However, the treatment did not lead to significant improvements in motor symptoms such as gait and bradykinesia, although there was a brief improvement in daily living activities, suggesting that longer or different rTMS protocols may be needed for better efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled study of 50-Hz repetitive transcranial magnetic stimulation for the treatment of Parkinson disease. Benninger, DH., Iseki, K., Kranick, S., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Wassermann, EM.[2022]

In untreated Parkinson's disease patients, repetitive transcranial magnetic stimulation (rTMS) of the dorsal premotor cortex (PMd) can normalize abnormal excitability in the primary motor cortex (M1), indicating that the connections between these areas are altered due to the disease.

After the first dose of l-dopa, the excitability changes in M1 induced by rTMS were reversed, suggesting that dopamine levels significantly influence the interaction between premotor and motor areas in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abnormal excitability of premotor-motor connections in de novo Parkinson's disease. Buhmann, C., Gorsler, A., Bäumer, T., et al.[2013]

In a study involving 12 patients with idiopathic Parkinson's disease, 0.2 Hz repetitive transcranial magnetic stimulation (rTMS) to the frontal cortex significantly improved daily living activities and motor scores, while occipital rTMS showed no significant clinical effects.

The study suggests that rTMS may have indirect effects on subcortical structures that contribute to symptom improvement, despite reduced regional cerebral blood flow (rCBF) in the stimulated areas, indicating a complex mechanism of action that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of successive repetitive transcranial magnetic stimulation on motor performances and brain perfusion in idiopathic Parkinson's disease. Ikeguchi, M., Touge, T., Nishiyama, Y., et al.[2019]

References

1. Austria pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation transiently reduces punding in Parkinson's disease: a preliminary study. [2021]

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

Akinesia in Parkinson's disease. II. Effects of subthreshold repetitive transcranial motor cortex stimulation. [2019]

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

Repetitive transcranial magnetic stimulation for levodopa-induced dyskinesias in Parkinson's disease. [2013]

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

The role of the inferior frontal gyri in cognitive processing of patients with Parkinson's disease: a pilot rTMS study. [2019]

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

Simultaneous repetitive transcranial magnetic stimulation does not speed fine movement in PD. [2019]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of Deep Repetitive Transcranial Magnetic Stimulation (drTMS) against Medical Refractory Symptoms in Parkinson Syndromes: First German Real-World Data with a Specific H5 Coil. [2022]

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

Controlled study of 50-Hz repetitive transcranial magnetic stimulation for the treatment of Parkinson disease. [2021]

9. Ireland pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Abnormal excitability of premotor-motor connections in de novo Parkinson's disease. [2013]

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

Effects of successive repetitive transcranial magnetic stimulation on motor performances and brain perfusion in idiopathic Parkinson's disease. [2019]