Deep Brain Stimulation of the Bilateral Habenula for Treatment-Refractory Obsessive-Compulsive Disorder

Obsessive-Compulsive Disorder Clinical Trial

Official title:

Deep Brain Stimulation of the Bilateral Habenula for Treatment-Refractory Obsessive-Compulsive Disorder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03463590
• Other study ID #: Habenula DBS for OCD
• Status: Recruiting
• Phase: N/A
• First received: February 28, 2018
• Last updated: March 27, 2018
• Start date: March 1, 2018
• Est. completion date: February 28, 2020

Study information

• Verified date: March 2018
• Source: Ruijin Hospital
• Contact: Yingying Zhang, MSc
• Phone: +086-17602137369
• Email: zhyy019[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: February 28, 2020
• Est. primary completion date: February 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Disease
• Obsessive-Compulsive Disorder

Intervention

Device:
• Bilateral surgical implantation of DBS system to habenula
The DBS device utilized in the present study may include the Medtronic, PINS and SceneRay DBS device depending on patients' choice.

Locations

Country	Name	City	State
China	Shanghai Ruijin Hospital Functional Neurosurgery	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Ruijin Hospital

Country where clinical trial is conducted

China, 

References & Publications (7)

Alonso P, Cuadras D, Gabriëls 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. — View Citation

Antolin-Fontes B, Ables JL, Görlich A, Ibañez-Tallon I. The habenulo-interpeduncular pathway in nicotine aversion and withdrawal. Neuropharmacology. 2015 Sep;96(Pt B):213-22. doi: 10.1016/j.neuropharm.2014.11.019. Epub 2014 Dec 2. Review. — View Citation

Batalla A, Homberg JR, Lipina TV, Sescousse G, Luijten M, Ivanova SA, Schellekens AFA, Loonen AJM. The role of the habenula in the transition from reward to misery in substance use and mood disorders. Neurosci Biobehav Rev. 2017 Sep;80:276-285. doi: 10.1016/j.neubiorev.2017.03.019. Epub 2017 May 30. Review. — View Citation

Boulos LJ, Darcq E, Kieffer BL. Translating the Habenula-From Rodents to Humans. Biol Psychiatry. 2017 Feb 15;81(4):296-305. doi: 10.1016/j.biopsych.2016.06.003. Epub 2016 Jun 7. Review. — View Citation

Fakhoury M. The habenula in psychiatric disorders: More than three decades of translational investigation. Neurosci Biobehav Rev. 2017 Dec;83:721-735. doi: 10.1016/j.neubiorev.2017.02.010. Epub 2017 Feb 13. Review. — View Citation

Hirschtritt ME, Bloch MH, Mathews CA. Obsessive-Compulsive Disorder: Advances in Diagnosis and Treatment. JAMA. 2017 Apr 4;317(13):1358-1367. doi: 10.1001/jama.2017.2200. Review. — View Citation

Kohl S, Baldermann JC. Progress and challenges in deep brain stimulation for obsessive-compulsive disorder. Pharmacol Ther. 2018 Jan 31. pii: S0163-7258(18)30018-4. doi: 10.1016/j.pharmthera.2018.01.011. [Epub ahead of print] Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Y-BOCSII Score	The score of the scale ranges from 0 to 50	Baseline (preoperative),1 month, 3 months,6 months, 9 months
Primary	Change in OCI-R Score	The score of the scale ranges from 0 to 72	Baseline (preoperative),1 month, 3 months,6 months, 9 months
Secondary	changes in the Hamilton Depression Scale(HAMD-17)	The score of the scale ranges from 0 to 50	Baseline(preoperative),1 month, 3 months, 6 months,9 months
Secondary	changes in the Hamilton Anxiety Scale(HAMA-14)	The score of the scale ranges from 0 to 56	Baseline(preoperative),1 month, 3 months, 6 months,9 months
Secondary	changes in FMRI signal	The FMRI signal is to estimate Blood Oxygenation Level Dependent (BOLD) and connectivity of brain areas	Baseline(preoperative),3 month, 6 months, 9 months
Secondary	changes in World Health Organization Quality of Life-BREF(WHO-BREF)		Baseline(preoperative),1 month, 3 months,6 months,9 months
Secondary	changes the MOS item short from health survey (SF-36)		Baseline(preoperative),1 month, 3 months,6 months,9 months
Secondary	Neuropsychological measures(Scores of cogstate battery)	Neuropsychological measures contains six tasks which are detection task, identification task, one card learning task, one back task, Groton maze learning task, set-shifting task	Baseline(preoperative),1 month, 3months,6months,9months