STN+NBM DBS for Mild Cognitive Impairment in Parkinson's Disease

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Helen M. Bronte-Stewart

Disqualifiers: Dementia, Seizures, Untreated depression, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to deep brain stimulation (DBS) to address both cognitive and movement issues in people with Parkinson's disease. The study aims to determine if using extra leads in the brain during DBS is safe and tolerable. Participants will undergo a specific type of surgery to explore how different surgical paths affect outcomes. Individuals with Parkinson's disease who are approved for DBS and willing to pause their medications for research checks might be suitable candidates. The trial will monitor participants closely over two years to evaluate the treatment's effects. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance future DBS treatments.

Will I have to stop taking my current medications?

The trial requires participants to be willing to stop their current medications when necessary for research visits.

What prior data suggests that this combined STN+NBM DBS approach is safe for treating cognitive and cognitive-motor symptoms in Parkinson's disease?

Research shows that deep brain stimulation (DBS) targeting the Subthalamic Nucleus (STN) is generally safe for treating movement problems in people with Parkinson's disease.

When researchers add the Nucleus Basalis of Meynert (NBM) as a target, studies indicate this method remains safe and feasible. Early results in conditions like Parkinson's disease dementia and Alzheimer's suggest that targeting the NBM does not cause serious safety issues.

In these studies, participants tolerated the combined DBS treatment well, with no major negative effects reported. Although this trial uses a slightly different path for the DBS leads, past research suggests that this combined approach is likely to be well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the combined STN+NBM DBS treatment for mild cognitive impairment in Parkinson's disease because it offers a novel approach to managing the condition. Unlike standard treatments that typically involve medications like Levodopa or dopamine agonists to manage motor symptoms, this technique uses deep brain stimulation (DBS) to target specific brain areas. The treatment is unique in its dual approach: one arm uses a lateral trajectory to stimulate the lateral efferent bundle from the nucleus basalis of Meynert (NBM), while the other uses a vertical trajectory to directly target the nucleus itself. This precise targeting could potentially improve cognitive function more effectively than existing therapies, which primarily focus on motor symptoms.

What evidence suggests that this combined STN+NBM DBS is effective for cognitive symptoms in Parkinson's disease?

This trial will explore the effects of Deep Brain Stimulation (DBS) on two specific brain areas to address thinking and memory problems in people with Parkinson's disease. Participants will receive combined STN + NBM DBS, with one group receiving the Lateral NBM Bundle Trajectory and another group receiving the Vertical Nuclear Trajectory. Previous studies have shown that DBS targeting the NBM can improve behavior and mood, suggesting possible benefits for thinking and memory. The NBM plays a role in these cognitive functions, so stimulating it might alleviate cognitive symptoms. Although data remains limited, these findings provide a reason to explore this combined approach further. ^{1 2 3 4 5}

Who Is on the Research Team?

Helen M Bronte-Stewart, MD MSE

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for individuals with Parkinson's disease who have mild cognitive impairment. They must be willing to adjust their medication for research visits, able to consent, approved for STN DBS surgery, and can walk 100 feet without help. It excludes pregnant individuals, those with unstable conditions or significant depression, dementia, a history of seizures, or the need for MRI.

Inclusion Criteria

I am approved for or planning on getting deep brain stimulation in the subthalamic nucleus.

Ability to provide informed consent

I am willing to stop my current medications for research visits if needed.

Exclusion Criteria

I need help to walk 100 feet.

Unstable medical, psychiatric conditions including significant untreated depression, history of suicidal attempt, or current suicide ideation

Pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Treatment

Participants undergo surgery for the placement of DBS leads in the STN and NBM, followed by initial treatment with novel stimulation patterns

4 weeks

1 visit (in-person)

Treatment and Monitoring

Participants receive ongoing DBS therapy with assessments at baseline and every six months, including neuropsychological evaluations, cognitive assessments, motor tasks, and questionnaires

104 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Combined STN+NBM DBS

Trial Overview The study tests a new deep brain stimulation method combining STN and NBM targeting both motor and cognitive symptoms in Parkinson's patients. Ten participants will receive this treatment over two years with regular assessments using neuropsychological evaluations and motor tasks.

How Is the Trial Designed?

Group I: Vertical Nuclear Trajectory Experimental Treatment 1 Intervention

Participants will receive combined STN + NBM DBS. The lead placed within the NBM will use a vertical trajectory targeting the nucleus itself.

Group II: Lateral NBM Bundle Trajectory Experimental Treatment 1 Intervention

Participants will receive combined STN + NBM DBS. The lead placed within the NBM will use a lateral trajectory targeting the lateral efferent bundle from the NBM

Who Is Running the Clinical Trial?

Helen M. Bronte-Stewart

Lead Sponsor

Trials

1

Recruited

10+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

In a study of 320 candidates for subthalamic deep brain stimulation (STN-DBS), 48% were found to have mild cognitive impairment (PD-MCI), with the majority classified as frontostriatal (80%) and a smaller group as posterior cortical (20%).

Patients with PD-MCI exhibited significant cortical thinning and changes in the left caudate nucleus and hippocampus compared to those with normal cognition, indicating that cognitive impairment in Parkinson's disease is associated with structural brain alterations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterogeneity of PD-MCI in Candidates to Subthalamic Deep Brain Stimulation: Associated Cortical and Subcortical Modifications. Devignes, Q., Daoudi, S., Viard, R., et al.[2022]

In a study of 24 patients undergoing subthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson's disease, significant declines in both semantic and phonemic verbal fluency were observed immediately after surgery and persisted for at least six months.

The acute decline in phonemic verbal fluency post-surgery may indicate a long-term deficit, but this cognitive impairment does not predict the development of Parkinson's disease dementia, which is more closely related to the disease itself rather than the surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does early verbal fluency decline after STN implantation predict long-term cognitive outcome after STN-DBS in Parkinson's disease? Borden, A., Wallon, D., Lefaucheur, R., et al.[2014]

In a study of 126 Parkinson's disease patients undergoing subthalamic nucleus deep brain stimulation (STN-DBS), those with mild cognitive impairment (MCI) experienced a lower risk of cognitive decline post-surgery compared to patients with normal cognitive function (NC).

Pre-operative cognitive status was identified as a significant predictor of post-operative cognitive changes, indicating that patients' cognitive abilities before surgery can influence their outcomes after STN-DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parkinson's disease with mild cognitive impairment may has a lower risk of cognitive decline after subthalamic nucleus deep brain stimulation: A retrospective cohort study. Xie, H., Zhang, Q., Jiang, Y., et al.[2022]

Subthalamic nucleus deep brain stimulation (STN-DBS) significantly improves motor function and quality of life in patients with Parkinson's disease, as shown in a study of 21 patients over 6 months.

While STN-DBS is considered safe regarding cognitive functions, there was a notable decline in phonemic verbal fluency, which may be linked to the progression of Parkinson's disease and a reduction in medication dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive effects of subthalamic nucleus stimulation in Parkinson's disease: a controlled study. Sáez-Zea, C., Escamilla-Sevilla, F., Katati, MJ., et al.[2022]

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease patients affects their ability to switch from automatic to controlled cognitive processing, particularly during tasks requiring higher cognitive load.

In a study of 15 Parkinson's patients, it was found that with STN DBS on, patients relied more on automatic counting strategies under increased cognitive load, while they could use more controlled strategies when DBS was off, indicating a load-dependent effect of STN DBS on cognitive control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Load-Dependent Interference of Deep Brain Stimulation of the Subthalamic Nucleus with Switching from Automatic to Controlled Processing During Random Number Generation in Parkinson's Disease. Williams, IA., Wilkinson, L., Limousin, P., et al.[2018]

In a study of 33 Parkinson's disease patients with high-frequency deep brain stimulation (DBS) in the internal Globus pallidus (GPi), unintentional stimulation of the nucleus basalis of Meynert (NBM) did not lead to a significant decline in cognitive function over one year.

These findings suggest that high-frequency NBM-DBS may not have the detrimental effects on cognition that were initially hypothesized, indicating a need for further research to explore the therapeutic potential of NBM-DBS in treating cognitive symptoms associated with Parkinson's disease dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serendipitous Stimulation of Nucleus Basalis of Meynert-The Effect of Unintentional, Long-Term High-Frequency Stimulation on Cognition in Parkinson's Disease. Bogdan, ID., Oterdoom, DLM., van Laar, T., et al.[2022]

A 75-year-old woman with Parkinson's disease experienced severe cognitive decline and developed dementia following deep brain stimulation (DBS) of the bilateral subthalamic nuclei, despite an initial brief improvement.

This case highlights the potential cognitive risks associated with STN DBS, suggesting that certain patients may be at higher risk for developing dementia after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dementia after DBS Surgery: A Case Report and Literature Review. Rektorova, I., Hummelova, Z., Balaz, M.[2021]

In a study of 26 elderly patients with Parkinson's disease undergoing subthalamic deep brain stimulation (STN-DBS), there was a higher incidence of serious adverse events, particularly psychosis and hallucinations, compared to younger patients from the EARLYSTIM study.

Despite these psychiatric complications being transient, the overall benefits of STN-DBS in improving Parkinson's symptoms were found to outweigh the risks, highlighting the importance of thorough psychiatric evaluations before and after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Older Candidates for Subthalamic Deep Brain Stimulation in Parkinson's Disease Have a Higher Incidence of Psychiatric Serious Adverse Events. Cozac, VV., Ehrensperger, MM., Gschwandtner, U., et al.[2020]

In a long-term study of 184 Parkinson's disease patients treated with subthalamic deep brain stimulation (STN-DBS), those with mild cognitive impairment (MCI) showed a higher prevalence of cognitive decline over time, with dementia affecting over 30% of these patients after 6 years.

Despite the cognitive challenges, STN-DBS demonstrated sustained efficacy on motor functions in both patients with MCI and those with normal cognition, indicating that the surgery remains beneficial for motor symptoms regardless of cognitive status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthalamic deep brain stimulation: clinical and neuropsychological outcomes in mild cognitive impaired parkinsonian patients. Merola, A., Rizzi, L., Artusi, CA., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05968703

Combined STN and NBM Deep Brain Stimulation for Mild ... The goal of this clinical trial is to evaluate the safety and tolerability of a novel deep brain stimulation (DBS) of the Subthalamic Nucleus (STN) and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12190852/

Nucleus Basalis of Meynert Volume and Cognitive ... Conclusions: Smaller NBM volume appears to be associated with PDD at baseline, but not with cognitive decline six months after STN DBS. Keywords ...

3. withpower.com withpower.com/trial/stnnbm-dbs-for-mild-cognitive-impairment-in-parkinsons-disease-e41f0

STN+NBM DBS for Mild Cognitive Impairment in ... This N/A medical study run by Helen M. Bronte-Stewart is evaluating whether Combined STN+NBM DBS will have tolerable side effects & efficacy for patients ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05320523

Simultaneous DBS of the GPi and the NBM in Patients ... This study aims to provide a proof of safety of combined bilateral Globus Pallidus internus (GPi) and Nucleus Basalis of Meynert (NBM) stimulation in patients ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7650115/

Combined subthalamic and nucleus basalis of Meynert ... However, an improvement in Neuropsychiatric Inventory (NPI) scores was observed in two patients with NBM-DBS. Case reports and small exploratory ...