Clinical trial NCT06660225: Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder
Official title: Towards Closed Loop Deep Brain Stimulation for Treatment of Refractory Obsessive-Compulsive Disorder
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Obsessive-Compulsive Disorder
Keywords: Obsessive
Compulsive
Deep Brain Stimulation
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2024-10-28
Enrollment: 10
Sex: ALL
Minimum age (years): 22
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: There will be two 4 month blocks in which, depending on group assignment, participants will receive either active or sham stimulation from the DBS device. Following completing of the first 4 month block, the groups will cross-over. Individuals originally receiving active stimulation will now receive sham, and individuals receiving sham stimulation originally will now receive active stimulation. Following the completing of both four month blocks, all participants will receive active open-label treatment. Continued follow-up psychiatric assessments will be preformed every two week during the double-blind portion of the trial, and then every 6 weeks during the open-label treatment phase.
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy of amSTN stimulation on OCD symptoms as measured by YBOCS
timeFrame: 36 months
measure: Incidence of Adverse events
timeFrame: 36 months
Secondary outcomes:
measure: Effect of DBS on Mood and Quality of Life as measured by HAM-A survey
timeFrame: 36 months
measure: Effect of DBS on Mood and Quality of Life as measured by HAM-D21 survey
timeFrame: 36 months
measure: Effect of DBS on Mood and Quality of Life as measured by BPRS survey
timeFrame: 36 months
measure: Effect of DBS on Mood and Quality of Life as measured by CGI-S survey
timeFrame: 36 months
measure: Effect of DBS on Mood and Quality of Life as measured by MMSE tool
timeFrame: 36 months
measure: Association between amSTN activity and cognitive/emotional measures as measured by rate of neural activity
timeFrame: 36 months
measure: Association between amSTN activity and cognitive/emotional measures as measured by amplitude of neural activity
timeFrame: 36 months
measure: Association between amSTN activity and cognitive/emotional measures as measured by phase
timeFrame: 36 months
measure: Association between amSTN activity and cognitive/emotional measures as measured by cross-frequency coupling of neural activity.
timeFrame: 36 months
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Nader Pouratian, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: