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

5 Participants Needed

Trial Summary

What is the purpose of this trial?

Apathy is a disabling neuropsychiatric symptom marked by reduced goal-directed behavior, including diminished interest, motivation, emotional expression, and social engagement. Though not formally defined in the DSM-V, apathy is common in several neurological and psychiatric disorders and significantly affects quality of life. In Parkinson's Disease (PD), it affects about 40% of patients and is associated with increased caregiver burden, reduced functional ability, and nearly threefold higher mortality. PD affects over 680,000 Americans today and is projected to impact more than 1.2 million by 2030. It presents with both motor symptoms (e.g., bradykinesia, tremor, rigidity) and non-motor symptoms like depression, anxiety, and apathy. While motor symptoms are often managed with dopaminergic medications and deep brain stimulation (DBS) targeting motor regions (e.g., subthalamic nucleus, globus pallidus internal), apathy typically persists or worsens following these treatments. No FDA-approved or consistently effective treatments exist for apathy in PD. Dopamine agonists may help but have side effects that limit long-term use. SSRIs and cholinesterase inhibitors may be tried for co-occurring depression or cognitive decline, but they are not indicated for apathy and can worsen symptoms or cause adverse effects in PD. This protocol proposes targeting apathy in PD using DBS of the ventral capsule/ventral striatum (VC/VS), a region involved in reward processing and goal-directed behavior. VC/VS DBS is FDA-approved under a Humanitarian Device Exemption for OCD and has shown promise in treating depression, addiction, and other disorders involving motivational deficits. Neuroimaging and preclinical models strongly implicate this region in the regulation of goal-directed behavior, reward sensitivity, and cognitive control-mechanisms disrupted in apathy. Stimulating VC/VS may improve motivation through fibers connected to orbitofrontal and anterior cingulate cortices (reward sensitivity) and dorsal prefrontal regions (cognitive control). Support for this approach comes from a case report where a patient with PD and OCD received both STN and VC/VS DBS. In addition to motor and OCD symptom improvement, the patient showed a significant reduction in apathy. Apathy worsened when stimulation ceased and improved again when resumed, suggesting a causal relationship. 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 DBS for apathy in PD. Building on extensive animal, imaging, and clinical data, it addresses a major unmet need using an existing DBS platform. The approach is supported by established neurocircuitry, prior clinical experience with VC/VS targeting, and early evidence suggesting potential benefit. It does not duplicate prior studies but extends DBS to a new, underserved indication within PD.

Research Team

Nora Vanegas-Arroyave, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Deep Brain Stimulation Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Nora Vanegas

Lead Sponsor

Trials

2

Recruited

20+