VC/VS for Apathy in PD

NCT06991335 | Not Yet Recruiting DMC FDA Device

• 1 other identifier: H-57525
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson Disease; Deep Brain Stimulation; Apathy

Keywords

parkinson disease; deep brain stimulation; apathy; dbs; pd; neuromodulation; imaging

Outcome Measures

Primary Outcomes (1)

• Changes in Apathy Symptoms

  Response will be defined as a reduction of ≥3 points on the Apathy Evaluation Scale (AES) and Clinical Global Impression Scale - Improvement (CGI-I) of 1 or 2 (indicating 1=very much improved or 2=much improved). Higher AES scores are associated with higher apathy levels. Lower CGI-I scores indicate greater improvement in the participant's condition.

  9 to 15 months

Study Arms (1)

Deep Brain Stimulation

EXPERIMENTAL

Device: Deep Brain Stimulation

Interventions

Deep Brain Stimulation DEVICE

Medtronic Percept PC with SenSight Directional Leads will be implanted to control the shape and size of stimulation

Deep Brain Stimulation

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Parkinson's Disorder as defined by the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (MDS-PD).
• 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.
• Documentation by primary neurologist of refractoriness to treatment for apathy with at least two dopamine-based treatments (e.g., levodopa, dopamine agonist) of sufficient dose and duration.
• Pre-DBS neuropsychological testing indicating normal cognition. Participants with mild cognitive impairment who have been evaluated by a cognitive neurologist for consideration of treatment (i.e., cholinesterase inhibitor) if indicated, may be included in the study once treatment has been stabilized for at least 2 months.
• Ability and willingness to give informed consent.
• Presence of a caregiver/informant who can complete study surveys/interviews related to the study participant.
• Stability of antidepressant medication dosing (i.e., SSRIs, Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), etc.) for a minimum of four weeks prior to surgery.

You may not qualify if:

• Major neurocognitive disorder (i.e., dementia) as determined by pre-DBS neuropsychological testing.
• Explanation of apathy symptoms by comorbid depression as determined by a psychiatric interview including the Montgomery and Asberg depression rating scale (MADRS). Individuals with a MADRS score ≥15 will be excluded.
• 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).
• Current PD-related psychosis (e.g., visual hallucinations).
• Any psychiatric, neurological and/or medical condition that makes the subject, in the opinion of the investigators, a poor candidate.
• Alcohol/substance use disorder, moderate or severe, within the previous 12 months.
• Female who is pregnant or breastfeeding or has plans to become pregnant in the next 24 months.
• Any contraindication for MRI.
• Presence of any of the following disorders: a) central nervous system infection, b) toxic-metabolic encephalopathy, defined as a syndrome of delirium associated with an identifiable toxin such as a chemical or metabolic disorder, c) multiple sclerosis, d) developmental delay.
• Need for diathermy.

Sponsors & Collaborators

• Nora Vanegas: lead

Study Sites (1)

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Parkinson Disease; Lethargy

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Study Officials

• Nora Vanegas-Arroyave, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nora Vanegas-Arroyave, MD

CONTACT

713-798-5060; nora.vanegasarroyave@bcm.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 20, 2025
• First Posted: May 27, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 1, 2032
• Study Completion (Estimated): September 1, 2032
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

US (1)