MRI to Study Deep Brain Stimulation Effects in Neurodegenerative Disease

Overseen By Tasnuva Hoque, BHA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Cognitive impairments, Speech deficits, others

Stay on Your Current Meds You can continue your current medications while participating

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

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how deep brain stimulation (DBS), a treatment using electrical impulses for brain disorders, affects brain activity and structure. Researchers aim to better understand DBS's impact on conditions like epilepsy, Alzheimer's, and depression by using advanced MRI technology. The trial seeks individuals who either plan to receive or already have DBS implants and can understand the study's purpose and provide consent. Participants will undergo MRI scans while researchers adjust DBS settings to determine if this can improve treatment outcomes. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance DBS treatment for various brain disorders.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this MRI technique is safe for studying deep brain stimulation effects?

Research has shown that deep brain stimulation (DBS) is generally safe and well-tolerated by patients. This treatment has been used for many years to help with conditions like Parkinson's disease, essential tremor, and dystonia, which causes muscle contractions. Studies have found that patients typically do not experience serious side effects from DBS. One report noted that DBS can improve thinking skills and quality of life early in the treatment. While some research highlights the benefits of DBS, other studies confirm its safety even if symptoms do not improve. Overall, DBS has a strong history as a safe option for many people with neurological conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about exploring the effects of fMRI-based programming in deep brain stimulation (DBS) for neurodegenerative diseases because it offers a personalized approach to treatment. Unlike standard DBS programming, which often relies on trial and error, this method uses real-time brain imaging to fine-tune stimulation settings. This could lead to more precise symptom control and potentially improve overall outcomes for patients. The ability to tailor DBS settings based on fMRI feedback represents a significant step forward in optimizing treatment effectiveness and enhancing patient quality of life.

What evidence suggests that this trial's treatments could be effective for neurodegenerative disease?

Research has shown that deep brain stimulation (DBS) is an effective treatment for conditions like Parkinson's disease, tremors, and OCD. For Alzheimer's disease, studies are exploring how DBS might help by influencing brain areas related to memory and thinking. Recent findings suggest that DBS could improve brain function by encouraging new cell growth in the hippocampus, a part of the brain important for memory. Additionally, using DBS in certain brain areas can activate circuits related to movement, which may help with symptoms in neurological diseases. While the exact effects on Alzheimer's and other conditions are still under investigation, early results are promising and support its potential effectiveness. Participants in this trial will undergo fMRI-based programming to optimize DBS settings, which may further enhance its therapeutic effects. ^{2 4 6 7 8}

Who Is on the Research Team?

Andres Lozano

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 with neurodegenerative diseases who are undergoing or have undergone deep brain stimulation (DBS) electrode implantation. They must understand the study and consent to participate, acknowledging they won't directly benefit from it. Those with serious cognitive impairments or communication issues, such as non-English speakers or those with speech deficits, cannot join.

Inclusion Criteria

Participants must be able to understand the purpose of this research and must sign the informed consent form

Participants must understand that the role of this research is to enhance our understanding of brain functioning and that he/she will not directly or indirectly benefit from the study

I am scheduled for or have had DBS electrode implantation.

Exclusion Criteria

Participants who are unable to effectively or efficiently communicate, for example patients suffering from speech deficits (dysarthria, aphasia) or are non-English speaking

I am able to understand and consent to participate in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Assessment

Patients undergo pre-operative MRI scans to assess brain structure and function before DBS implantation

3 months

Multiple visits for MRI scans

Post-operative Follow-up

Patients undergo fMRI scanning with different DBS settings to aid in programming and assess therapeutic effects

1 year

Regular visits for fMRI and clinical assessments

Long-term Follow-up

Participants are monitored for safety and effectiveness of DBS therapy over an extended period

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Deep Brain Stimulation (DBS)
• fMRI

Trial Overview The trial uses advanced MRI technology to perform functional magnetic resonance imaging (fMRI) on patients with DBS implants. The goal is to observe how DBS affects brain function and explore if fMRI can help improve clinical practices for these patients.

How Is the Trial Designed?

Group I: fMRI-based programming Experimental Treatment 1 Intervention

DBS patients will undergo fMRI scanning while on different stimulation settings. The results will be fed to the programming clinician (movement disorder neurologist) to aid the conventional programming process at the clinician's discretion.

Deep Brain Stimulation (DBS) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Deep Brain Stimulation for:

• Advanced Parkinson's disease
• Medically refractory tremor
• Dystonia
• Obsessive-compulsive disorder

Approved in European Union as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Dystonia
• Psychiatric conditions

Approved in Canada as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Dystonia

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

Using a body-transmit coil for cranial MRI in patients with deep brain stimulation (DBS) devices can lead to increased electrode heating, but remains within safe limits at 1.5T, with temperature increases below 1°C under controlled conditions.

At 3T, cranial MRI can exceed safety guidelines for heating, indicating that careful monitoring and specific protocols are essential for safely conducting fMRI studies in DBS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety of Using Body-Transmit MRI in Patients with Implanted Deep Brain Stimulation Devices. Kahan, J., Papadaki, A., White, M., et al.[2022]

A study using the Deep Brain Stimulation Brain Tissue Network's database found no adverse clinical or pathological effects from performing 1.5 T MRI scans on patients with implanted DBS devices, suggesting that MRI is relatively safe for these patients.

Further examination of post-mortem brains with DBS leads exposed to prolonged 3T MRI also showed no evidence of heat-related damage, supporting the safety of higher field strength MRI in DBS patients under current guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of human brain tissue post-magnetic resonance imaging: information from the National Deep Brain Stimulation Brain Tissue Network (DBS-BTN). Ullman, M., Vedam-Mai, V., Krock, N., et al.[2011]

A study involving 249 deep brain stimulation (DBS) patients who underwent 445 MRI sessions found no adverse events related to the MRI scans, indicating that brain MRI at 1.5 Tesla is safe for DBS patients.

The study highlighted that the specific absorption rates (SAR) during scans were higher than current product labeling allows, suggesting a need for updated safety guidelines for MRI use in DBS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of brain MRI after deep brain stimulation hardware implantation. Nazzaro, JM., Lyons, KE., Wetzel, LH., et al.[2010]

The study established an effective MRI protocol using MPRAGE T1W, FSE T2W, and ME-GRE sequences for clear visualization of brain targets and electrodes in patients undergoing deep brain stimulation (DBS), involving 29 patients and healthy controls.

Despite the severe imaging artifacts caused by DBS electrodes, these artifacts can be beneficial for accurately locating the electrodes, enhancing the reliability of postoperative imaging assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging patients pre and post deep brain stimulation: Localization of the electrodes and their targets. Li, Y., Buch, S., He, N., et al.[2021]

Deep brain stimulation is an effective treatment for movement disorders, involving an implanted electrode and pulse generator, but its mechanisms of action are not fully understood and were developed without extensive preclinical safety studies.

Complication rates for deep brain stimulation can exceed 25%, with 4-6% of patients experiencing permanent neurological issues, highlighting the need for better understanding of adverse events and safer stimulation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety considerations for deep brain stimulation: review and analysis. Grill, WM.[2007]

Deep Brain Stimulation (DBS) for Parkinson's disease can lead to rare complications, such as an intracranial abscess, as demonstrated in a case involving a 59-year-old male who developed significant inflammation and required multiple surgeries after the procedure.

Despite the complications, the patient's Parkinson's symptoms improved after the abscess was surgically drained, suggesting that the abscess may have inadvertently provided some therapeutic benefit similar to a subthalomotomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. Brandão, E., Rosas, MJ., Abreu, P., et al.[2013]

Deep brain stimulation (DBS) is generally safe and effective for treating movement disorders, but this case highlights a rare complication: a cerebral infarction following DBS surgery in a patient with cervical dystonia.

The ischemia may have been caused by high-amplitude microstimulation, potentially leading to small-vessel vasospasm, indicating that while DBS is beneficial, careful monitoring of stimulation parameters is crucial to avoid such complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral ischemia related to globus pallidus internus stimulation for cervical dystonia. Kang, DW., Kim, HY., Chang, JW.[2011]

In a study of 40 Parkinson's disease patients undergoing subthalamic deep brain stimulation (STN-DBS), 45% reported significant improvement in sleep quality at 6 months, although this improvement was not statistically significant at 12 months.

The most common benefits included better overall sleep quality and maintenance, but some patients experienced new-onset daytime sleepiness, indicating that while STN-DBS can improve sleep, the effects can vary widely among individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in Parkinson's disease sleep symptoms and daytime somnolence after bilateral subthalamic deep brain stimulation in Parkinson's disease. Kharkar, S., Ellenbogen, JR., Samuel, M., et al.[2020]

Deep brain stimulation (DBS) is a surgical treatment for neurological disorders that can be enhanced by using ultrahigh-field (UHF) MRI for planning, which allows for greater precision in targeting areas of the brain.

Using UHF MRI improves the clinical efficacy of DBS by enabling a more individualized approach to treatment, potentially leading to better outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra High Field MRI-Guided Deep Brain Stimulation. Forstmann, BU., Isaacs, BR., Temel, Y.[2018]

Deep brain stimulation (DBS) for advanced Parkinson's disease, using Multiple Sequences Image Fusion (MuSIF) for accurate targeting, led to a significant reduction of 76% in L-dopa equivalent daily dose after 3 months.

Patients experienced a 50% reduction in dyskinesias and a 45% decrease in motor fluctuations, demonstrating the efficacy of the combined imaging techniques in improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple sequential image-fusion and direct MRI localisation of the subthalamic nucleus for deep brain stimulation. Rampini, PM., Locatelli, M., Alimehmeti, R., et al.[2017]

Deep brain stimulation (DBS) has been explored as a treatment for dementia, with three studies focusing on its effects, including one on fornix DBS for Alzheimer's disease and two on nucleus basalis of Meynert for Alzheimer's and Parkinson's disease dementia.

Current evidence for the effectiveness of DBS in treating dementia is still preliminary and limited, indicating a need for further research to understand its potential clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for the treatment of Alzheimer disease and dementias. Laxton, AW., Lozano, AM.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6397644/

Deep brain stimulation: current challenges and future directions ... treatment plans in highly refractory patients. DBS in Alzheimer disease. AD is the most common neurodegenerative condition and is marked by progressive ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2949669125000016

Effectiveness of DBS as a treatment for Alzheimer's disease Nevertheless, neuromodulation is gaining more attention in studies of neurodegenerative diseases, with an emphasis on Deep Brain Stimulation (DBS). In this ...

3. nature.com nature.com/articles/s41531-025-01124-7

Chronic adaptive deep brain stimulation for Parkinson's ... While continuous deep brain stimulation (cDBS) is an effective therapy ... German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.

4. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2839117

Long-Term Personalized Adaptive Deep Brain Stimulation ... We report the results of the Adaptive DBS Algorithm for Personalized Therapy in Parkinson Disease ... Neurodegenerative Disease Research project ( ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03115814

Deep Brain Stimulation for Treatment of Severe ... ... deep brain stimulation ... Diseases. Nervous System Diseases. Tauopathies. Neurodegenerative Diseases. Neurocognitive Disorders. Mental Disorders. Alzheimer ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2667049622000278

Deep brain stimulation in neurological diseases and other ... The FDA first approved deep brain stimulation in 1997 to treat essential tremor, in 2002 it was approved for Parkinson's disease, in 2003 for dystonia and in ...

7. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2838886

Five-Year Outcomes from Deep Brain Stimulation of the ... From screening, a significant improvement in motor outcomes is reported 1 year after deep brain stimulation (DBS) and sustained out to 5 years.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12004396/

Efficacy and Safety of Bilateral Deep Brain Stimulation ... All patients tolerated DBS well, with no serious adverse effects reported. Early on, DBS significantly improved cognitive function and quality ...