Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder

Towards Closed Loop Deep Brain Stimulation for Treatment of Refractory Obsessive-Compulsive Disorder

The goal of this clinical trial is to learn if deep brain stimulation (DBS) works to treat refractory obsessive-compulsive disorder (OCD). The main questions it aims to answer are:

• Assess the effects of the anteromedial sub-thalamic nucleus (amSTN)stimulation on obsessive/compulsive symptoms.
• Map the amSTN using neuronal responses [single unit and local field potentials (LFP) recordings] at rest and under high frequency stimulation during surgery.
• Record chronic brain activity with the implanted pulse generator and look for neuronal signatures correlated with symptom severity.

Researchers will compare active deep brain stimulation to a placebo (sham stimulation) to see if DBS works to treat refractory OCD.

Participants will:

• Undergo surgery for the implantation of a deep brain stimulation device
• Follow-up visits every three weeks with study staff
• 6 month follow-up for the next 2-3 years after first year of study participation is complete

Study Overview

• Status: Recruiting
• Conditions: Obsessive-Compulsive Disorder
• Intervention / Treatment: Device: Medtronic Percept Deep Brain Stimulation Therapy [Sham Control Stimulation]; Device: Medtronic Percept Deep Brain Stimulation Therapy [Therapeutic stimulation]

Detailed Description

The primary goal of this research study is to conduct a small scale randomized, double-blind clinical cross-over trial of deep brain stimulation for obsessive-compulsive disorder targeting the anteromedial subthalamic nucleus (amSTN), with which study team will not only produce high quality data of the clinical efficacy of DBS for OCD, but also attain critical insights into the neurophysiological underpinnings of disease and symptoms in OCD. This work will support future innovative therapy development, including refinement of surgical targeting and optimization of therapeutic stimulation.

This will be a 3-year study with the aim of implanting 10 patients with bilateral amSTN DBS leads. Intra-operatively, precise single neuron recordings will be obtained at the therapeutic target while the patient participates symptom provocation. Participants will be implanted with a sensing pulse generator (Medtronic Percept) which enables chronic recordings from the amSTN target in addition to providing therapeutic stimulation. Each participant will be randomized to start with either a sham control stimulation phase or therapeutic stimulation, and cross-over at 4 months. If symptoms recur upon cross-over from therapeutic to sham stimulation, participants will exit the sham stimulation phase and rescue therapy/stimulation will be delivered. All participants will transition to an open label stimulation phase for chronic therapy. Multiple assessments of the participants will follow, including OCD severity, cognition, behavior, and side effects.

Formal psychiatric assessments will take place at two weeks, at one month, and then once every three weeks during the randomization blinded period and then every 6 weeks during the open label period. During psychiatric assessments, the PERCEPT device will be used to obtain neural recordings of the STN activity.

Additionally, for the secondary outcome measure for the association between amSTN activity and cognitive/emotional measure there are two components of this measure that are of a qualitative nature. Burstiness and coherence are unitless measures and thus will not be included in the outcome measure reporting section. They will instead be discussed in the limitation section at annual reporting.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nader Pouratian, M.D., Ph.D.; Phone Number: 2146486630; Email: Nader.Pouratian@UTSouthwestern.edu
• Study Contact Backup: Name: Tash Mupambo; Phone Number: 214-645-1355; Email: Tashinga.Mupambo@UTSouthwestern.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
      • Contact: Nader Pouratian, M.D., Ph.D.; Phone Number: 310/274-2095; Email: Nader.Pouratian@UTSouthwestern.edu
      • Sub-Investigator: Kala Bailey, M.D.
      • Principal Investigator: Nader Pouratian, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with a diagnosis of obsessive-compulsive disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM) 5 criteria
• Severe OCD assessed by the Yale-Brown Obsessive-Compulsive Scale (YBOCS) with a score of more than 27
• Refractory OCD; severe symptoms and impairment for more than 5 years despite pharmacological and psychological treatment.
• Have failed to improve following treatment with at least two serotonin transport inhibitors and one augmenting agent taken for an adequate time period.
• Having failed to improve despite adequate cognitive behavioral therapy, as evaluated by the study psychiatrist
• Patients between 22 and 75.
• Ability to understand and sign written informed consent by the patient.

Exclusion Criteria:

• Diagnosis of severe major depression disorder (MDD) with psychotic features.
• Significant suicidal risk [Hamilton Depression scale item 3 (suicide)>2].
• Comorbidity with any primary Psychotic Disorder, Post-Traumatic Stress Disorder (PTSD), or Eating Disorder.
• History of substance or alcohol dependence or abuse in the preceding 12 months.
• Significant cognitive decline, measured by Mini-Mental State Examination (MMSE <26) and Montreal Cognitive Assessment (MoCA; <24).
• Any other current clinical significant neurological disorder or medical illness affecting brain function, other than a tic disorder.
• Any clinically significant abnormality on preoperative MRI that would affect the safety of the surgical procedure in the opinion of the study neurosurgeon.
• Any DBS contraindication, infection, coagulopathy, significant cardiac risk factors, or other medical risk factors for surgery.
• Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sham Control stimulation, then Therapeutic stimulation; Subject randomized to this arm are initially "OFF" DBS (Deep Brain Stimulation) prior to the open label period for 16 weeks and then "ON" DBS for the next 16 weeks. This is then followed by an open-label period of DBS stimulation.	Device: Medtronic Percept Deep Brain Stimulation Therapy [Sham Control Stimulation]; Deep brain stimulation is a surgery where bilateral electrodes are precisely inserted to specific brain targets affected by a disease state, and electrical stimulation is applied to achieve symptom relief. DBS is a reversible and adjustable treatment option and is now a preferred alternative to neurosurgical ablation. Sham Stimulation=DBS OFF; Device: Medtronic Percept Deep Brain Stimulation Therapy [Therapeutic stimulation]; Deep brain stimulation is a surgery where bilateral electrodes are precisely inserted to specific brain targets affected by a disease state, and electrical stimulation is applied to achieve symptom relief. DBS is a reversible and adjustable treatment option and is now a preferred alternative to neurosurgical ablation. Therapeutic Stimulation= DBS ON
Experimental: Therapeutic stimulation, then Sham Control stimulation; Subjects randomized to this arm are initially "ON" DBS prior to the open label period for 16 weeks and then "OFF" DBS for the next 16 weeks. This is followed by an open-label stimulation period.	Device: Medtronic Percept Deep Brain Stimulation Therapy [Sham Control Stimulation]; Deep brain stimulation is a surgery where bilateral electrodes are precisely inserted to specific brain targets affected by a disease state, and electrical stimulation is applied to achieve symptom relief. DBS is a reversible and adjustable treatment option and is now a preferred alternative to neurosurgical ablation. Sham Stimulation=DBS OFF; Device: Medtronic Percept Deep Brain Stimulation Therapy [Therapeutic stimulation]; Deep brain stimulation is a surgery where bilateral electrodes are precisely inserted to specific brain targets affected by a disease state, and electrical stimulation is applied to achieve symptom relief. DBS is a reversible and adjustable treatment option and is now a preferred alternative to neurosurgical ablation. Therapeutic Stimulation= DBS ON
Experimental: Therapeutic stimulation; All participants will transition to an open label stimulation phase for chronic therapy after the cross-over portion of this trial	Device: Medtronic Percept Deep Brain Stimulation Therapy [Therapeutic stimulation]; Deep brain stimulation is a surgery where bilateral electrodes are precisely inserted to specific brain targets affected by a disease state, and electrical stimulation is applied to achieve symptom relief. DBS is a reversible and adjustable treatment option and is now a preferred alternative to neurosurgical ablation. Therapeutic Stimulation= DBS ON

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of amSTN stimulation on OCD symptoms as measured by YBOCS	Assessment of the efficacy of amSTN stimulation on OCD symptoms. This will be assessed by the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Possible scores range from 0-5 where lower scores indicate better outcome.	36 months
Incidence of Adverse events	Safety will be assessed with cumulative serious adverse event rate that will be Frequency at which AEs occur that are directly related to the study device.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of DBS on Mood and Quality of Life as measured by HAM-A survey	Hamilton Scale for Anxiety. A rating scale developed to measure the severity of anxiety symptoms. The scale consists of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and semantic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score ranger of 0-56, where 17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.	36 months
Effect of DBS on Mood and Quality of Life as measured by HAM-D21 survey	Hamilton Depression Rating Scale (HAM-D). A 21-item version of the HAM-D that includes 4 items intended to subtype the depression. The HAM-D is originally a 17 item questionnaire pertaining to symptoms of depression experienced over the past week. The patients score is determined using the first 17 questions. A score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher (indicating at least moderate severity) is usually required for entry into a clinical trial. Scoring on each question varies.	36 months
Effect of DBS on Mood and Quality of Life as measured by BPRS survey	Brief Psychiatric Rating Scale (BPRS). An assessment that assesses the level of the following symptoms; somatic concern, anxiety, emotional withdrawal, conceptual disorganization, guilt feelings, tension, mannerisms and posturing, grandiosity, depressive mood, hostility, suspiciousness, hallucinatory behavior, motor retardation, uncooperativeness, unusual thought content, blunted affect, excitement, disorientation. Items are scored on a 1(not present) to 7 (extremely severe) scale. It is based on the clinicians interview with the patients and observations of the patient behavior over the previous 2-3 days.	36 months
Effect of DBS on Mood and Quality of Life as measured by CGI-S survey	Clinical Global Inventory- Severity scale is used to measure this outcome (CGI-S). This is a 3-item observer-rated scale that measures illness severity (CGI-S). The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through 7 (amongst the most severely ill patients).	36 months
Effect of DBS on Mood and Quality of Life as measured by MMSE tool	Mini-Mental State Examination (MMSE). A questionnaire comprised of 11 questions that is used by doctors and other health professionals to check for cognitive impairment. It is typically used to see if you have problems with ones thinking or communication. It can check for problems with understanding and amnesia. The MMSE checks 6 areas of mental ability including; knowing when one is (date and place), attention and concentration, short-term memory (recall), language skills, visual and spatial relationship between objects, ability to understand and follow instructions. The assessment is scored out of 30. A score of 25 or higher is normal, and score below 24 could indicate cognitive impairment.	36 months
Association between amSTN activity and cognitive/emotional measures as measured by rate of neural activity	The rate of neural activity will be measured via Hz.	36 months
Association between amSTN activity and cognitive/emotional measures as measured by amplitude of neural activity	Amplitude of neural activity will be measured via microamps.	36 months
Association between amSTN activity and cognitive/emotional measures as measured by phase	A unit of measurement used to quantify the relationship between the temporal structures of signals in the brain, and are often used to study functional connectivity in neuroscience. This outcome measure will be measured in units of 0-2π.	36 months
Association between amSTN activity and cognitive/emotional measures as measured by cross-frequency coupling of neural activity.	Cross-frequency coupling (CFC) is a neuroscience measure that describes the statistical relationship between the frequency, amplitude, or phase of two different frequency bands in the brain. Its a type of neural oscillatory coupling that is been studied in the context of brain health and disease. This data point will be measured via the modulation index.	36 months

Collaborators and Investigators

• Sponsor: Nader Pouratian
• Investigators: Principal Investigator: Nader Pouratian, M.D., Ph.D., University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): January 1, 2031

Study Registration Dates

• First Submitted: October 5, 2024
• First Submitted That Met QC Criteria: October 23, 2024
• First Posted (Actual): October 28, 2024

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Deep Brain Stimulation; Obsessive; Compulsive
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Obsessive-Compulsive Disorder
• Other Study ID Numbers: STU-2024-0733

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Investigators with established research programs will be eligible for data sharing. Interested investigators will be required to submit a summary of proposed work and requested data elements. If approved by the Principal Investigator of the study, data will be shared. This data will be de-identified and coded. There is no plan to share identifiers outside the study team.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No