Clinical trial NCT03463590: Deep Brain Stimulation of the Bilateral Habenula for Treatment-Refractory Obsessive-Compulsive Disorder
Official title: Deep Brain Stimulation of the Bilateral Habenula for Treatment-Refractory Obsessive-Compulsive Disorder
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obsessive-Compulsive Disorder
Keywords: Habenula
Obsessive-Compulsive Disorder
Deep brain stimulation
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2018-03-13
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All subjects will receive bilateral surgical implantation of DBS system
Primary purpose: TREATMENT

Brief summary: Deep brain stimulation (DBS) offers an effective and safe treatment for patients with debilitating, otherwise treatment-refractory obsessive-compulsive disorder(OCD). Although several target areas for DBS have been used for OCD, such as the ventral capsule/ventral striatum and the subthalamic nucleus, not all patients show a clinical response, varying from 10% to 61.5%. Exploring new DBS targets may be a key approach to improve this situation. The habenula is an evolutionarily conserved structure playing an important role in depression, punishment avoiding, reward, addiction, pain and circadian rhythms. The habenula can be considered a promising target for OCD treatment based on the following hypotheses and clinical observations.

1. The lateral habenula DBS has significant clinical antidepressant effects.
2. The habenula plays an important role in the regulation of dopamine and serotonin systems.
3. Selective serotonin reuptake inhibitors, the first line treatment for OCD, are commonly used to treat clinical depression.
4. The habenula serves as a 'negative reward center' that mediates or moderates stress, negative emotions and thoughts, aversive learning, and goal-directed behavior, which are core clinical symptoms and signs of OCD.
5. In our hospital, DBS of the habenula produced a significant improvement in OCD symptoms in one patient who failed to respond to other treatments, including capsulotomy either alone or in combination combined with cingulumotomy.

These theoretical and clinical considerations indicate that the habenula can be seen as a promising DBS target for OCD treatment. This study is focused on the effectiveness of bilateral DBS of the habenula for patients with treatment-refractory OCD. Furthermore, the study is aimed at exploring the influence of DBS of the habenula on brain activity and cognition.


Eligibility criteria: Inclusion Criteria:

* Diagnosed as having primary OCD according to DSM-IV criteria using the Structured Clinical Interview for DSM-IV Axis I disorders;
* YBOCSII score ≥31；
* Duration ≥2 years；
* Refractoriness to therapy was defined as no response or insufficient response following at least 2 treatments with adequate trials or intolerance to two or three selective serotonin transporter inhibitors (SSRIs) and clomipramine, augmentation strategies (antipsychotics) and cognitive behavioral therapy.
* Capacity to provide informed consent (understanding of the study purpose and methods.

Exclusion Criteria:

* Except for those with major depressive disorder and mild anxiety disorders, patients with clinically significant comorbid DSM-IV diagnoses (such as schizophrenia, bipolar II disorder, alcohol or substance abuse in the last 6 months, current tic disorder, or body dysmorphic disorder)
* Patients with severe personality disorders, assessed using the Structured Clinical Interview for DSM-IV Axis II disorders.
* Serious and unstable organic diseases (e.g. unstable coronal heart disease);
* Pregnancy and/or lactation.

Primary outcomes:
measure: Change in Y-BOCSII Score
timeFrame: Baseline (preoperative),1 month, 3 months,6 months, 9 months
measure: Change in OCI-R Score
timeFrame: Baseline (preoperative),1 month, 3 months,6 months, 9 months
Secondary outcomes:
measure: changes in the Hamilton Depression Scale(HAMD-17)
timeFrame: Baseline（preoperative）,1 month, 3 months, 6 months,9 months
measure: changes in the Hamilton Anxiety Scale(HAMA-14)
timeFrame: Baseline（preoperative）,1 month, 3 months, 6 months,9 months
measure: changes in FMRI signal
timeFrame: Baseline（preoperative）,3 month, 6 months, 9 months
measure: changes in World Health Organization Quality of Life-BREF(WHO-BREF)
timeFrame: Baseline（preoperative）,1 month, 3 months,6 months,9 months
measure: changes the MOS item short from health survey (SF-36)
timeFrame: Baseline（preoperative）,1 month, 3 months,6 months,9 months
measure: Neuropsychological measures(Scores of cogstate battery)
timeFrame: Baseline（preoperative）,1 month, 3months,6months,9months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Ruijin Hospital Functional Neurosurgery
state: Shanghai
Study officials:
References:
citation: Alonso P, Cuadras D, Gabriels L, Denys D, Goodman W, Greenberg BD, Jimenez-Ponce F, Kuhn J, Lenartz D, Mallet L, Nuttin B, Real E, Segalas C, Schuurman R, du Montcel ST, Menchon JM. Deep Brain Stimulation for Obsessive-Compulsive Disorder: A Meta-Analysis of Treatment Outcome and Predictors of Response. PLoS One. 2015 Jul 24;10(7):e0133591. doi: 10.1371/journal.pone.0133591. eCollection 2015.
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