DBS for Treatment-resistant Obsessive-compulsive Disorder

The Effect of Deep Brain Stimulation (DBS) in Treatment-resistant Obsessive-compulsive Disorder (TR-OCD)

The primary purpose of this study is to investigate the effect of deep brain stimulation (DBS) implantation targeting the anteromedial region of subthalamic nucleus (amSTN), or nucleus accumbens (NAc), or bed nucleus of the stria terminalis (BNST), or ventral capsule/ventral striatum (VC/VS), or the ventral anterior limb of the internal capsule (vALIC) in patients with treatment-resistant obsessive-compulsive disorder (TR-OCD).

Study Overview

• Status: Not yet recruiting
• Conditions: Obsessive-Compulsive Disorder (OCD)
• Intervention / Treatment: Device: Deep brain stimulation (DBS)

Detailed Description

At least 40-60% of people with obsessive-compulsive disorder (OCD) continue to have symptoms after drug treatment. There is still a lack of effective therapies for TR-OCD. In a comprehensive survey of diverse neuromodulation therapies, targeting specific nuclei with DBS has the most potential for OCD with apparent symptoms. The stimulation targets of DBS for patients with TR-OCD include vALIC, BNST, amSTN, VC/VS, and NAc. For the target site of each individual, it depends on the individualized evaluation results made by the study team. Although DBS is effective and tolerable and has the potential to improve the lives of many patients with TR-OCD, evidence remains limited. To explore its effectiveness, this project plans to conduct DBS-targeted vALIC, BNST, amSTN, VC/ VS, or NAc on RT-OCD patients.

Another goal of this program is to study the neuronal activity of the vALIC, BNST, amSTN, VC/VS, and NAc, respectively. At the same time, some subjects are presented with a task involving an unexpected reward. This separate study is an option and will not affect current study participation.

Some participants will also be invited to join a related study that involves positron emission tomography (PET) scanning to determine how the stimulation changes activity in the brain. Participation in the separate PET study is optional and will not affect current study participation.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaolei Liu, MD & PhD; Phone Number: +861083198650; Email: ring@vip.163.com
• Study Contact Backup: Name: Wenfeng Zhao, MD; Phone Number: +861083198650; Email: fengfeng_zw@ccmu.edu.cn

Study Locations

• China
  • Beijing, China, 100053
    • Xuanwu Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. aged 18-65;
2. able to provide written informed consent;
3. have a diagnosis of OCD according to the Statistical Manual of Mental Disorders-Fourth Edition-Text Revised (DSM-IV-TR) criteria and confirmed by the Mini-International Neuropsychiatric Interview Chinese version 5.0;
4. have failed to improve despite undergoing two distinct courses of selective serotonin reuptake inhibitors (SSRIs), each lasting a minimum of 3-6 months; have failed to yield therapeutic efficacy after the administration of the maximum dose of clomipramine for 3-6 months in a single trial; without achieving effectiveness under cognitive behaviour therapy for six months; have failed to achieve therapeutic efficacy after three months of atypical antipsychotic medications, singularly or in combination with SSRIs or clomipramine.

Exclusion Criteria:

1. presence of other psychotic disorders;
2. have a treatment history that includes electroconvulsive therapy (ECT), modified electroconvulsive therapy (MECT), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), DBS, and transcranial magnetic stimulation (TMS);
3. presents a suicide risk (defined as a HAMD-17 score of ≥3 on suicide-related items);
4. experience difficulty in effectively communicating with investigators;
5. with a history of traumatic brain injury (TBI);
6. with intracranial or cardiovascular stents;
7. substance abuse within the past six months;
8. unstable neurological or coagulation disorders;
9. women who are pregnant, lactating, or of childbearing potential who refuse the use of reliable contraception during the study;
10. have been involved in other clinical studies within three months before enrollment in this study;
11. any conditions unsuitable for conducting this study program considered by the study group.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment-resistant obsessive-compulsive disorder (TR-OCD).; Patients will undergo bilateral DBS lead implantation.	Device: Deep brain stimulation (DBS); The DBS lead is stereotactically introduced into the target in the brain (vALIC, BNST, amSTN, VC/VS, or NAc) and fixed to the skull; the lead is then connected to a neurostimulator implanted subcutaneously in the subclavicular region.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yale-Brown Obsessive Compulsive Scale (Y-BOCS): the change from baseline to 1 year in the Y-BOCS total score.	The Y-BOCS scale is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms), yielding a total possible score range from 0 to 40. The total score is usually computed from the subscales for obsessions (items 1-5) and compulsions (items 6-10). The results can be interpreted based on the total score: 0-7 is sub-clinical; 8-15 is mild; 16-23 is moderate; 24-31 is severe; 32-40 is extreme.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yale-Brown Obsessive Compulsive Scale (Y-BOCS): remission, response, and partial response rate	remission (defined as Y-BOCS total score ≤16) at Week 2, Month 1, Month 3, Month 6, and Month 12; response is a ≥35% reduction in Y-BOCS total score from baseline to Week 2, Month 1, Month 3, Month 6, and Month 12; partial response is a 25%~34% reduction in Y-BOCS total score from baseline to Week 2, Month 1, Month 3, Month 6, and Month 12. The Y-BOCS scale is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms), yielding a total possible score range from 0 to 40. The total score is usually computed from the subscales for obsessions (items 1-5) and compulsions (items 6-10). The results can be interpreted based on the total score: 0-7 is sub-clinical; 8-15 is mild; 16-23 is moderate; 24-31 is severe; 32-40 is extreme.	Week 2, Month 1, Month 3, Month 6, and Month 12
Hamilton Anxiety Scale (HAMA): the change from baseline to 2 weeks, 1 month, 3 months, 6 months, and 1 year in the HAMA total score.	HAMA is a 14-item test measuring the severity of anxiety symptoms. The total anxiety score ranges from zero to 56, with higher scores indicating more anxiety. The seven psychic anxiety items elicit a psychic anxiety score that ranges from 0 to 28. The remaining seven items yield a somatic anxiety score ranging from 0 to 28.	Week 2, Month 1, Month 3, Month 6, and Month 12
Hamilton Depression Rating Scale (HAMD-17): the changes of HAMD-17 scores and its subscales from baseline to 2 weeks, 1 month, 3 months, 6 months, and 1 year.	HAMD-17 ranges from 0 to 52, with higher scores indicating more depression; a score of 20 or more indicates moderate to severe depression.	Week 2, Month 1, Month 3, Month 6, and Month 12
Pittsburgh Sleep Quality Index (PSQI): the change of PSQI from baseline to Week 2, Month 1, Month 3, Month 6, and Month 1.	Consisting of 19 items, the PSQI measures several aspects of sleep, offering seven component scores and one composite score. The component scores consist of subjective sleep quality, sleep latency (i.e., how long it takes to fall asleep), sleep duration, habitual sleep efficiency (i.e., the percentage of time in bed that one is asleep), sleep disturbances, use of sleeping medication, and daytime dysfunction. Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality.	Week 2, Month 1, Month 3, Month 6, and Month 12
Clinical Global Impression-Severity (CGI-S): the change from baseline to 2 weeks, 1 month, 3 months, 6 months, and 1 year in Clinical Global Impression-Severity (CGI-S)	The clinical global impression-severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment. Score 1 presents normal, not at all ill, and score 7 presents among the most extremely ill patients.	Week 2, Month 1, Month 3, Month 6, and Month 12
Clinical Global Impression-Improvement (CGI-I): CGI-I score at Week 2, Month 1, Month 3, Month 6, and Month 12.	The clinical global impression-improvement scale (CGI-I) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. Score 1 presents the patient as much improved, and score 7 presents much worse.	Week 2, Month 1, Month 3, Month 6, and Month 12
EuroQol-5 Dimension-level Scale (EQ-5D-5L): the change from baseline to Week 2, Month 1, Month 3, Month 6, and Month 12 in EQ-5D-5L.	EQ-5D-5L is an instrument that evaluates the generic quality of life. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The score ranges from 5 (having no problems) to 25 (being unable to do/having extreme problems).	Week 2, Month 1, Month 3, Month 6, and Month 12
Young Mania Rating Scale (YMRS): the change from baseline to Week 2, Month 1, Month 3, Month 6, and Month 12.	This scale has 11 items and is based on the patient's subjective report of his or her clinical condition over the previous 48 hours. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. Scores range from 0 to 60, with higher scores indicating more severe mania. A score of 0 to 5 means no obvious manic symptoms; a score of 6 to 10 means definite manic symptoms; a score of 22 or above means severe manic symptoms. It will be used as a systematic screen for DBS-induced mania or hypomania. Although scores above 8 have been considered evidence of manic symptomatology in bipolar patients, the unmasked physician will use this scale and screening questions to assess whether any hypomanic symptoms require clinical intervention including DBS adjustment.	Week 2, Month 1, Month 3, Month 6, and Month 12
Safety as indicated by the number of Adverse Events Week 2, Month 1, Month 3, Month 6, and Month 12.	Possible Adverse Events include: Major and minor adverse events will be evaluated by Adverse Events Questionnaire (AEQ) and accompanying Case Report Form (AEQ CRF) in multiple domains, including psychiatric, neurological, and cognitive effects. The AEQ includes cognitive and behavioral screening items used in the Xuanwu DBS clinic for movement disorder patients. Additionally, we have added items for the adverse events observed in pilot DBS for OCD.	Week 2, Month 1, Month 3, Month 6, and Month 12

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Investigators: Principal Investigator: Hongxing Wang, MD & PhD, Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Estimated): April 20, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: April 8, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: OCD, DBS
• Additional Relevant MeSH Terms: Mental Disorders; Personality Disorders; Anxiety Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder
• Other Study ID Numbers: DBS for TR-OCD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No