Obsessive-Compulsive Disorder
Conditions
Keywords
Obsessive, Compulsive, Deep Brain Stimulation
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.
Interventions
DEVICEMedtronic 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
DEVICEMedtronic 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
Sponsors
Nader Pouratian
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Neither the participant of investigator will know which treatment group an individual is assigned to. After the completion of the blinded portion of the trial, all participants will be transitioned to open-label stimulation/treatment.
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.
Eligibility
Sex/Gender
ALL
Age
22 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of amSTN stimulation on OCD symptoms as measured by YBOCS | 36 months | 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. |
| Incidence of Adverse events | 36 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of DBS on Mood and Quality of Life as measured by HAM-A survey | 36 months | 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. |
| Effect of DBS on Mood and Quality of Life as measured by HAM-D21 survey | 36 months | 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. |
| Effect of DBS on Mood and Quality of Life as measured by BPRS survey | 36 months | 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. |
| Effect of DBS on Mood and Quality of Life as measured by CGI-S survey | 36 months | 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). |
| Effect of DBS on Mood and Quality of Life as measured by MMSE tool | 36 months | 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. |
| Association between amSTN activity and cognitive/emotional measures as measured by rate of neural activity | 36 months | The rate of neural activity will be measured via Hz. |
| Association between amSTN activity and cognitive/emotional measures as measured by amplitude of neural activity | 36 months | Amplitude of neural activity will be measured via microamps. |
| Association between amSTN activity and cognitive/emotional measures as measured by phase | 36 months | 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. |
| Association between amSTN activity and cognitive/emotional measures as measured by cross-frequency coupling of neural activity. | 36 months | 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. |
Countries
United States
Contacts
CONTACTNader Pouratian, M.D., Ph.D.
CONTACTTash Mupambo
PRINCIPAL_INVESTIGATORNader Pouratian, M.D., Ph.D.
University of Texas Southwestern Medical Center
Outcome results
None listed