Deep Brain Stimulation for Apathy in Parkinson's Disease

Overseen By Nora Vanegas-Arroyave, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Nora Vanegas

Must be taking: Dopamine-based treatments

Disqualifiers: Dementia, Depression, Psychosis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 9 to 15 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to help people with Parkinson's Disease who struggle with severe apathy, a lack of motivation or interest that can affect daily life. The study uses deep brain stimulation (DBS) in a specific brain area linked to motivation and reward. This method, known as VC/VS Deep Brain Stimulation, has shown promise in other conditions like depression and addiction. People diagnosed with Parkinson's, who have experienced severe apathy for at least two years, and have not improved with standard treatments might be suitable for this trial. As an unphased trial, this study offers a unique opportunity to explore innovative treatments that could enhance quality of life.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, your antidepressant medication dose must be stable for at least four weeks before surgery.

What prior data suggests that this deep brain stimulation technique is safe for treating apathy in Parkinson's Disease?

Research has shown that Deep Brain Stimulation (DBS) targeting the ventral capsule/ventral striatum (VC/VS) might safely treat lack of motivation in people with Parkinson's Disease. The FDA has already approved DBS for conditions like Obsessive-Compulsive Disorder (OCD). In one case, a patient with both Parkinson's and OCD experienced reduced apathy when DBS targeted the VC/VS area. When the stimulation was turned off, apathy worsened, but it improved again when DBS was restarted. This suggests that VC/VS DBS might aid in motivation and goal-setting.

This use of DBS has shown promise without worsening movement problems. The available data reports no major side effects, which is encouraging. While more research is needed, early findings suggest that VC/VS DBS could be well-tolerated and helpful in reducing apathy in Parkinson’s patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for apathy in Parkinson's disease, such as medications and behavioral therapies, aim to manage symptoms but often have limited effectiveness. Deep Brain Stimulation (DBS) is unique because it directly targets specific brain areas involved in motivation and mood. Specifically, the VC/VS (ventral capsule/ventral striatum) region is stimulated, which is thought to influence apathy more directly. Researchers are excited about this approach as it offers a new mechanism of action, potentially providing relief for symptoms that are hard to treat with current options.

What evidence suggests that VC/VS Deep Brain Stimulation is effective for apathy in Parkinson's Disease?

Research has shown that deep brain stimulation (DBS) in the ventral capsule/ventral striatum (VC/VS) might help reduce apathy in people with Parkinson's Disease (PD). This trial will investigate the effects of VC/VS DBS on apathy in PD patients. The VC/VS is crucial for feeling rewarded and motivated, which can be impaired in individuals with apathy. In one case, a person with PD felt more motivated when this brain area was stimulated and less motivated when the stimulation stopped. This suggests that stimulating the VC/VS might help reduce apathy. Although more studies are needed, current evidence indicates that VC/VS DBS can be safe and might boost motivation without worsening PD's movement problems. ^{2 6 7 8 9}

Who Is on the Research Team?

Nora Vanegas-Arroyave, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for Parkinson's Disease (PD) patients who suffer from apathy, a condition where they have little interest or motivation. It's not for everyone with PD; only those struggling with this specific non-motor symptom and who haven't found relief through standard treatments.

Inclusion Criteria

Presence of severe apathy as determined by apathy criteria established by the International Society for Central Nervous System Clinical Trials and Methodology Apathy Working Group (ISCTM-AWG)

Apathy severity of -9 to +36, on the Lille Apathy Rating Scale (LARS) for at least 2 years

Ability and willingness to give informed consent

Exclusion Criteria

Major neurocognitive disorder (i.e., dementia) as determined by pre-DBS neuropsychological testing

History of suicide attempt in the past 36 months or current active suicidal ideation (Yes to #2-5 on the Columbia Suicide Severity Rating Scale - C-SSRS)

Any psychiatric, neurological and/or medical condition that makes the subject, in the opinion of the investigators, a poor candidate

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Deep Brain Stimulation (DBS) targeting the ventral capsule/ventral striatum (VC/VS) for apathy in Parkinson's Disease

9 to 15 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VC/VS Deep Brain Stimulation

Trial Overview The trial is testing Deep Brain Stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS), areas of the brain involved in motivation and reward. The study aims to see if stimulating these regions can reduce apathy in PD patients by improving their drive and engagement.

How Is the Trial Designed?

Group I: Deep Brain Stimulation Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Nora Vanegas

Lead Sponsor

Trials

2

Recruited

20+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06991335

Study Details | NCT06991335 | VC/VS for Apathy in PD VC/VS DBS was safe, did not impair motor symptoms, and appeared to enhance motivation. This study aims to test the safety and efficacy of VC/VS ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6395396/

Comparison of Efficacy of Deep Brain Stimulation of Different ... The main finding of our study is that among the different DBS targets, GPi and STN showed better efficacy than other targets. Furthermore, the ...

3. nature.com nature.com/articles/s41467-025-60695-4

Boundary complexity of cortical and subcortical areas ... Despite its efficacy in alleviating PD motor symptoms in many patients, outcomes following DBS exhibit significant variability, with instances ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666459325000599

Comparing the impact of low frequency vs high ... Among 126 pooled patients from 8 RCTs, it was found that LFS significantly improved gait stability, swallowing, and verbal fluency with minimal adverse effects.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11175766/

Unlocking the future of deep brain stimulation The effectiveness and safety of DBS therapy, in comparison to alternative medical treatments or neurological procedures, can exhibit variability ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5673773/

Target-specific deep brain stimulation of the ventral capsule ... The DBS method described here is widely used to treat Parkinson's disease, essential tremor, dystonia, and other movement disorders, as well as treatment- ...

7. jnnp.bmj.com jnnp.bmj.com/content/94/5/379

Structural and functional correlates of the response to deep ... We investigated functional and structural connectivities related to and predictive of clinical effectiveness of DBS at ventral capsule/ventral striatum region ...

8. jneurosci.org jneurosci.org/content/43/45/7575

Advances in Deep Brain Stimulation: From Mechanisms to ... Deep brain stimulation (DBS) is a surgical therapy involving the implantation of electrodes into target brain regions to deliver stimulation.

9. sciencedirect.com sciencedirect.com/science/article/pii/S1094715921000891

Ventral Capsule/Ventral Striatum Stimulation in Obsessive- ... Our findings show that in VC/VS stimulation, the neural network associated with clinical outcome shows overlap with that of previously described for other ...