NCT02655926

Brief Summary

The overarching aim is to compare the effects of ventral capsule/ventral striatum (VC/VS) and subthalamic nucleus (STN) deep brain stimulation (DBS) in the same participants. Investigators will test the hypothesis, grounded in cognitive neuroscience, that DBS at both sites is better than either site alone for treating the symptom dimensions of obsessive compulsive disorder (OCD). Specifically, Investigators will employ novel cognitive paradigms and neurophysiological measures of cortical synaptic function to test the hypothesis that VS/VC and STN DBS have different mechanisms of action and that alleviation of OCD symptoms is mediated by improvement in mood/anxiety with VS/VC DBS and by directly interrupting obsessions and compulsions with STN DBS. Investigators will additionally determine whether adjunctive cognitive behavioural therapy (CBT) enhances the response to DBS by providing the cognitive and behavioural skills to optimise symptom management and daily function.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Sep 2012

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2012

Completed
2.9 years until next milestone

First Submitted

Initial submission to the registry

July 17, 2015

Completed
6 months until next milestone

First Posted

Study publicly available on registry

January 14, 2016

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2016

Completed
Last Updated

March 3, 2017

Status Verified

July 1, 2015

Enrollment Period

4.2 years

First QC Date

July 17, 2015

Last Update Submit

March 1, 2017

Conditions

Obsessive-Compulsive Disorder

Keywords

OCDDBSDeep Brain Stimulation

Outcome Measures

Primary Outcomes (1)

  • Improvement of OCD symptoms on YBOCS scale greater than or equal to 35%

    15 months

Study Arms (2)

STN Arm

ACTIVE COMPARATOR

Participants would only have STN deep brain stimulation switched at optimal settings for that participant on for 12 weeks.

Procedure: Deep Brain Stimulation

VC/VS Arm

ACTIVE COMPARATOR

Participants would only have VC/VS deep brain stimulation switched on at optimal settings for that participant for 12 weeks.

Procedure: Deep Brain Stimulation

Interventions

Deep Brain StimulationPROCEDURE

Participants undergo implantation of bilateral electrodes at both the VS/VC and STN sites through a single burr hole under general anaesthesia. High-resolution MRI scans are used to calculate target coordinates and to verify accurate electrode location post-surgery. Each STN electrode have 4 electrical contacts at its distal tip (with a 0.5mm separation) and each VS/VC electrode have 4 electrical contacts at its distal tip (with a 1.5mm separation) to allow fine tuning of the exact site for stimulation delivery. Two non-rechargeable batteries (Activa PC) are connected to the electrodes and positioned under the skin of the right and left chest wall so that they correspond to the same set of electrodes for each patient: one for the 2 STN electrodes and one for the 2 VC/VS electrodes.

Also known as: DBS
STN ArmVC/VS Arm

Eligibility Criteria

Age20 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Participants must have undergone intensive treatment and have demonstrable treatment resistance as defined by:
  • At least two serotonin reuptake inhibitors (SRI) for a minimum of 12 weeks at optimal British National Formulary (BNF) doses.
  • Augmentation of SRI treatment with antipsychotic drugs administered at maximally tolerated doses or by extending the selective serotonin reuptake inhibitor (SSRI) dose beyond BNF limits.
  • Two trials of CBT of at least 10 hours.
  • Failed inpatient treatment for OCD.
  • Participants must be older than 20 years of age.
  • Confirmation of a primary diagnosis of obsessive compulsive disorder (International Classification of Diseases (ICD 10) F42.0-F42.9).
  • Duration of OCD of at least 10 years.
  • At least 2 years of unremitting symptoms despite intensive psychopharmacological and psychological treatment or failure to sustain, over a 3 month period, a response to inpatient psychological treatment by at least 33% with accompanying optimised pharmacological therapy.
  • A minimum score of 32 on Yale Brown Obsessive Compulsive Scale (YBOCS) thus constituting profound illness and a maximum score of 50 on the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) General Assessment of Function Scale (GAF).
  • Ability to provide sustained informed consent.

You may not qualify if:

  • Current diagnosis of Substance misuse (ICD10 F10-F19)
  • Current diagnosis of Organic brain syndrome (ICD10 F00-F09)
  • Current diagnosis of Adult personality disorder (ICD10 F60-F69)
  • Current diagnosis of Pervasive developmental disorder (ICD10 F84)
  • Current diagnosis of Schizophrenia (ICD10 F20-F29)
  • Current diagnosis of Bipolar disorder (ICD 10 F30-31)
  • Contraindications to neurosurgery
  • Pregnancy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UCL Institute of Neurology

London, WC1N 3BG, United Kingdom

Location

Related Publications (9)

  • Storch EA, Murphy TK, Geffken GR, Sajid M, Allen P, Roberti JW, Goodman WK. Reliability and validity of the Yale Global Tic Severity Scale. Psychol Assess. 2005 Dec;17(4):486-91. doi: 10.1037/1040-3590.17.4.486.

    PMID: 16393016BACKGROUND

  • Storch EA, Rasmussen SA, Price LH, Larson MJ, Murphy TK, Goodman WK. Development and psychometric evaluation of the Yale-Brown Obsessive-Compulsive Scale--Second Edition. Psychol Assess. 2010 Jun;22(2):223-32. doi: 10.1037/a0018492.

    PMID: 20528050BACKGROUND

  • Welter ML, Mallet L, Houeto JL, Karachi C, Czernecki V, Cornu P, Navarro S, Pidoux B, Dormont D, Bardinet E, Yelnik J, Damier P, Agid Y. Internal pallidal and thalamic stimulation in patients with Tourette syndrome. Arch Neurol. 2008 Jul;65(7):952-7. doi: 10.1001/archneur.65.7.952.

    PMID: 18625864BACKGROUND

  • Stefani A, Lozano AM, Peppe A, Stanzione P, Galati S, Tropepi D, Pierantozzi M, Brusa L, Scarnati E, Mazzone P. Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson's disease. Brain. 2007 Jun;130(Pt 6):1596-607. doi: 10.1093/brain/awl346. Epub 2007 Jan 24.

    PMID: 17251240BACKGROUND

  • Ferraye MU, Debu B, Fraix V, Goetz L, Ardouin C, Yelnik J, Henry-Lagrange C, Seigneuret E, Piallat B, Krack P, Le Bas JF, Benabid AL, Chabardes S, Pollak P. Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease. Brain. 2010 Jan;133(Pt 1):205-14. doi: 10.1093/brain/awp229. Epub 2009 Sep 22.

    PMID: 19773356BACKGROUND

  • Cif L, Biolsi B, Gavarini S, Saux A, Robles SG, Tancu C, Vasques X, Coubes P. Antero-ventral internal pallidum stimulation improves behavioral disorders in Lesch-Nyhan disease. Mov Disord. 2007 Oct 31;22(14):2126-9. doi: 10.1002/mds.21723.

    PMID: 17853483BACKGROUND

  • Krack P. Subthalamic stimulation for Parkinson's disease: a new benchmark. J Neurol Neurosurg Psychiatry. 2011 Apr;82(4):356-7. doi: 10.1136/jnnp.2010.222497. Epub 2011 Feb 18. No abstract available.

    PMID: 21335569BACKGROUND

  • Morein-Zamir S, Craig KJ, Ersche KD, Abbott S, Muller U, Fineberg NA, Bullmore ET, Sahakian BJ, Robbins TW. Impaired visuospatial associative memory and attention in obsessive compulsive disorder but no evidence for differential dopaminergic modulation. Psychopharmacology (Berl). 2010 Oct;212(3):357-67. doi: 10.1007/s00213-010-1963-z. Epub 2010 Jul 27.

    PMID: 20661550BACKGROUND

  • Robbins TW. Shifting and stopping: fronto-striatal substrates, neurochemical modulation and clinical implications. Philos Trans R Soc Lond B Biol Sci. 2007 May 29;362(1481):917-32. doi: 10.1098/rstb.2007.2097.

    PMID: 17412678BACKGROUND

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Anxiety DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation TherapyTherapeuticsSurgical Procedures, Operative

Study Officials

  • Eileen M Joyce, PhD

    University College, London

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 17, 2015

First Posted

January 14, 2016

Study Start

September 1, 2012

Primary Completion

November 1, 2016

Study Completion

November 1, 2016

Last Updated

March 3, 2017

Record last verified: 2015-07

Locations

GB(1)