Identifying factors that help predict improvement with deep brain stimulation (a surgical treatment) for obsessive-compulsive disorder

Recruiting

• Conditions: Mixed obsessional thoughts and acts,

• Registration Number: CTRI/2020/03/024131
• Lead Sponsor: Wellcome Trust DBT India Alliance

Brief Summary

**Key goals & hypotheses:**The current proposal aims to identify biomarkers that predict treatment response to deep brain stimulation (DBS) over subthalamic nucleus (STN) in subjects with chronic and refractory obsessive-compulsive disorder (OCD). We hypothesize that baseline STN-prefrontal connectivity, low frequency oscillatory activity over frontal lobes/STN and impaired performance on response inhibition/response conflict tasks would predict improvement in OCD.

**Rationale:** STN is a component of cortico-striato-thalamo-cortical circuit implicated in OCD. Electrophysiological activity and neural connectivity of STN contribute to OCD relevant neurocognitive functioning, such as response inhibition and conflict monitoring. DBS may improve OCD by modulating STN connectivity and electrophysiological activity mediated by the effects on neurocognitive functioning.

**Study design:**We plan to perform DBS over STN in 24 subjects with treatment-refractory OCD. Structural/functional imaging, electrophysiological recording and neurocognitive assessment would be performed at baseline. The subjects would undergo structured clinical assessment for 12 months post-surgery.  A group of 24 healthy volunteers and 24 subjects with treatment-refractory OCD who do not undergo surgery would be recruited as comparison subjects for comparing the biomarkers. Baseline biomarkers would be tested as predictors for clinical response. Neuroadaptive changes would be studied through reassessment of neurocognitive functioning and electroencephalographic activity post-DBS.

**Impact:** Identification of predictors would help in patient selection and understand the mechanism of action of this invasive and expensive treatment, paving way for innovations such as closed loop stimulation.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-01-04
• Last Update Posted: 2020-03-18

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• i.Age between 18 to 60 years.
• ii.Primary diagnosis of obsessive-compulsive disorder satisfying the DSM-5 criteria2 , established using Mini International Neuropsychiatric Interview-7.0.2. .
• iii.Duration of OCD  5 years.
• iv.Yale-Brown Obsessive Compulsive Scale (YBOCS) score of  28 or  14 if the subject has either predominantly obsessions or compulsions alone.
• v.Clinical Global Impressions – Severity (CGI-S) scale of  5 vi.Disability of  40% as evaluated by Indian Disability Evaluation and Assessment Scale (IDEAS).
• vii.Failure to obtain meaningful improvement in OCD despite adequate trial with standard treatment strategies which should include: a.At least 3 trials of serotonin reuptake inhibitors (SRIs), one of which should be clomipramine, which were either ineffective or poorly tolerated.
• An adequate trial includes recommended dose of SRIs for  12 weeks duration each46.
• b.Augmentation of SRIs with at least 2 agents for  6 weeks, one of which should be either risperidone or aripiprazole.
• c.Trial of structured behaviour therapy/cognitive behaviour therapy for at least 20 sessions or demonstrated inability to tolerate the anxiety due to therapy.

Exclusion Criteria

• Diagnosis of bipolar disorder, psychotic disorder of ³ 3 months duration as assessed with MINI-7.0.2 ii.
• Current substance use disorder (except caffeine or nicotine use disorder) or Major depressive episode or current high suicidality, as assessed with MINI-7.0.2. iii.
• Severe personality disorder as assessed with Structured Clinical Assessment of DSM-5-PD version iv.
• Clinically significant abnormality on magnetic resonance imaging (MRI) of the brain.
• Pregnancy, contraindication for DBS/anaesthesia/preoperative MRI, inability to comply with surgical requirements.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Yale Brown Obsessive Compulsive severity scale (Y-BOCS)	Yale Brown Obsessive Compulsive severity scale (Y-BOCS)

Secondary Outcome Measures

Name	Time	Method
Clinical Global Impressions-severity, Hamilton depression rating scale, Hamilton anxiety rating scale, WHO-Quality of life -BREF, WHO-Disability Assessment Schedule	12 months post-surgery, assessment conducted every 1 months

Trial Locations

Locations (1)

National Institute of Mental Health and Neuro Sciences; 🇮🇳 Bangalore, KARNATAKA, India

National Institute of Mental Health and Neuro Sciences

🇮🇳Bangalore, KARNATAKA, India

Shyam Sundar Arumugham

Principal investigator

9008600112

a.shyamsundar@gmail.com