Deep Brain Stimulation and Obsessive-compulsive Disorder (STOC2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University Hospital, Bordeaux
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT01329133
First received: April 4, 2011
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

Obsessive-compulsive disorder (OCD) is a relatively common psychiatric condition, which is classically treated by antidepressant medications in combination with psychotherapies. However, both these conventional therapeutic approaches fail to sufficiently improve obsessive-compulsive symptoms in 20-30% of cases. From these considerations, deep brain stimulation (DBS), as a reversible and adjustable surgical procedure, has recently been introduced in the field of resistant OCD. DBS currently uses electrodes with four contacts on each lead, which are bilaterally implanted into the chosen brain structure. DBS consists of the delivery of a high-frequency current through the quadripolar electrodes connected to a battery powered pulse-generating device. Several clinical investigations have shown that DBS, primarily targeting either the ventral striatum (VS) or the subthalamic nucleus (STN), as brain sites of interest because of their particular involvement in the production of OCD symptoms, is able to produce an approximately 40% or greater reduction in clinical symptom intensity in severely chronic and incapacitating forms of OCD. These promising findings lead to propose a comparison of the efficacy, safety and tolerability of DBS choosing either the VS or STN as brain target by conducting a large controlled trial and including a medico-economic analysis for assessing the classical cost/efficacy ratio. In this way, the present study is expected to promote and highlight the importance of DBS, as an effective, safe, well-tolerated and cost-relevant surgical approach for the management of resistant OCD.


Condition Intervention Phase
Obsessive-Compulsive Disorder
Procedure: Deep Brain Stimulation (DBS)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment of Severe and Resistant Obsessive-compulsive Disorder by High-frequency Stimulation of the Ventral Striatum and the Subthalamic Nucleus

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • Combination of three criteria (composite criterion), as follows: a. Y-BOCS score ≤ 16 / and b. Technical feasibility (each leads in the target) / and c. Safety, as assessed by any serial adverse event [ Time Frame: Month 13 : one year after stimulation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Remission as defined by a Y-BOCS score ≤ 16 at M13 [ Time Frame: Month 13 : one year after stimulation ] [ Designated as safety issue: Yes ]
  • Number of electrode contacts correctly located within the chosen brain target (0, 1 or 2) [ Time Frame: End of surgical procedure (day 1) ] [ Designated as safety issue: Yes ]
  • Monitoring of psychological and somatic complaints made spontaneously by the patient over the course of the present trial, in combination to the semi-structured interview for collecting side effects [ Time Frame: Every 3 months from Month 1 to Month 13 ] [ Designated as safety issue: Yes ]
  • Scores on neuropsychological tests exploring all executive functions [ Time Frame: Every 3 months from Month 1 to Month 13 ] [ Designated as safety issue: Yes ]
  • Percentage change in the total Y-BOCS score from M1 to M13 [ Time Frame: Every 3 months from Month 1 to Month 13 ] [ Designated as safety issue: Yes ]
  • Therapeutic response, as indicated by a 35% decrease or more in the Y-BOCS score and a score of 1 or 2 (very much or much improved) on the CGI improvement scale from M1 to M13 [ Time Frame: Every 3 months from Month 1 to Month 13 ] [ Designated as safety issue: Yes ]
  • Percentage change in the Y-BOCS obsessive and compulsive subscores from M1 to M13 [ Time Frame: Every 3 months from Month 1 to Month 13 ] [ Designated as safety issue: Yes ]
  • Percentage change in the overall Padua Inventory score, MADRS score, BAS score from M1 to M13 [ Time Frame: Every 3 months from Month 1 to Month 13 ] [ Designated as safety issue: Yes ]
  • Percentage change in the total and depression and anxiety subscale scores on the HAD scale from M1 and M13 [ Time Frame: Every 3 months from Month 1 to Month 13 ] [ Designated as safety issue: Yes ]
  • Ratings of functional disability and quality of life [ Time Frame: Every 3 months from Month 1 to Month 13 ] [ Designated as safety issue: Yes ]
  • Correlations between efficacy and anatomical positioning of both stimulation electrodes within the chosen brain target [ Time Frame: Every 3 months from Month 1 to Month 13 ] [ Designated as safety issue: Yes ]
  • cost comparison of therapeutic strategies [ Time Frame: M-13 and M13 (one year after stimultaion) ] [ Designated as safety issue: No ]
    cost comparison of thérapeutic strategies : classical versus surgical

  • Cost / effectiveness ration [ Time Frame: M-13/ M13 (one year after stimulation) ] [ Designated as safety issue: No ]
    Cost / effectiveness ratio : cost difference between therapeutic strategies and success rate of DBS

  • Cost-utility rati [ Time Frame: every 3 months from month 1 to month 13 ] [ Designated as safety issue: No ]
    Cost-utility ratio based on SF-36 scores.


Estimated Enrollment: 28
Study Start Date: April 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: DBS of subthalamic nucleus Procedure: Deep Brain Stimulation (DBS)
In a first time: Implantation of DBS electrodes, stereotactically, in each hemisphere into the targeted brain structure under local anesthesia. In a second time (next week): installation of the deep brain neurostimulator and connection to the electrodes implanted under general anesthesia. And one month later: beginning of the stimulation.
Active Comparator: DBS of ventral striatum Procedure: Deep Brain Stimulation (DBS)
In a first time: Implantation of DBS electrodes, stereotactically, in each hemisphere into the targeted brain structure under local anesthesia. In a second time (next week): installation of the deep brain neurostimulator and connection to the electrodes implanted under general anesthesia. And one month later: beginning of the stimulation.

Detailed Description:

Obsessive-compulsive disorder (OCD) is a relatively common psychiatric condition with an estimated lifetime prevalence of 2-3 % of the general population. It is generally characterized by a chronic course leading to a profound impairment in psychosocial functioning and to a marked deterioration in quality of life. Today, the well-established efficacy of antidepressants, acting preferentially by blocking serotonin reuptake, in addition to psychological treatments, have considerably changed the poor prognosis of the illness. However, both conventional therapeutic approaches failed to substantially alleviate obsessive-compulsive symptoms in 20-30% of cases. Deep brain stimulation, as a reversible and adjustable surgical procedure, has recently been introduced in the field of OCD, primarily targeting either the ventral striatum (VS) or the subthalamic nucleus (STN) and leading to an approximately 40% or greater reduction in clinical symptom intensity from baseline levels in severely chronic and resistant forms of OCD. These promising findings lead to propose a comparison of the efficacy, safety and tolerability of DBS choosing either the VS or STN as brain target by conducting a multicenter, parallel-group, randomized, single-blind trial over a 13-month follow-up period. For this purpose, a total population of 28 OCD patients who meet the currently used operational criteria for defining therapeutic resistance will be recruited. The surgical procedure will consist in the implantation of stimulation electrodes with four contacts on each lead, which are stereotactically and bilaterally implanted into the targeted brain structure under local anesthesia. Per-operative, single-unit electrophysiological recordings of the neuronal activity will be performed using five parallel microelectrodes and serving as guide for the implantation of both definitive electrodes. They will be connected to a battery powered pulse-generating device five days later under general anesthesia. Thereafter, psychiatric assessments including both the Y-BOCS ("Yale-Brow Obsessive-compulsive scale") and PI ("Padua Inventory") for measuring OCD symptom severity, the BAS ("Brief Anxiety Scale"), MADRS ("Montgomery and Asberg Depression rating Scale") and HAD ("Hospital Anxiety and Depression Scale") for determining anxiety and/or depressive symptom intensity, and the CGI ("Clinical Global Impression") rating scales for evaluating global symptom severity and treatment response will be performed every 3 months beyond the one-month postoperative free-stimulation period. This will be coupled with a large battery of neuropsychological tests exploring all executive functions in combination with precise medical records of side effects for appreciating safety/tolerability of DBS. A cost-effectiveness analysis, as a formal method of comparing DBS and classical therapeutic strategies with regard to their respective resource utilization (costs) and outcomes (effectiveness) will also be carried out. Therefore, the present study may contribute to highlight the special interest of DBS, as an effective, safe, well-tolerated and cost-relevant surgical approach for the management of resistant OCD.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age comprised between 18 and 60 years
  • History of OCD for at least 5 years according to the DSM-IV-TR criteria and characterized by a "good insight", as determined by the BABS ("Brown Assessment of Beliefs Scale")
  • Severe form of OCD, as evidenced by:

    • a score ≥ 25 on the Y-BOCS
    • a score > 4 on the CGI scale
    • a score =< 40 on the GAF ("global assessment of functioning)
  • Lack of therapeutic effects of at least 3 antidepressants selectively blocking serotonin reuptake (SSRI) at least 12 consecutive weeks at the maximal tolerated dose (up to 80 mg/day for fluoxetine, 300 mg/day for fluvoxamine, 200 mg/day for sertraline, 60 mg/day for paroxetine, 60mg/day for citalopram and 250 mg/day for clomipramine) prescribed alone and in combination for at least 1 month with: 1) risperidone or olanzapine or aripiprazole or quetiapine, 2) clomipramine
  • Lack of therapeutic effects of behavioral therapy with two different therapists using conventional techniques primarily based on exposure with prevention of ritualized response
  • Understand and accept the design and constraints of the present study
  • Be a beneficiary or member of health insurance plan
  • Provide written consent to the study after receiving clear information

Exclusion Criteria:

  • Patient with cognitive impairment with a Mattis scale score ≤ 130
  • Patient with other DSM-IV-TR axis I diagnoses (schizophrenia, bipolar, substance abuse or substance dependence), except for generalized anxiety disorder, social phobia or nicotine dependence
  • Patient with high suicide risk, as indicated by a score ≥ 2 on the MADRS (item 10)
  • Patient with personality disorder corresponding to the clusters A and B, as assessed with the SIDP-IV ("Structured Interview for DSM-IV Personality")
  • Patient with contraindication for MRI scanning, abnormal brain MRI or serious intercurrent disease
  • Patient with contraindication for surgery or anesthesia
  • Patient currently treated with anticoagulant or antiplatelet drug
  • Be a woman of childbearing age without effective contraception
  • Be hospitalized under constraint
  • Be under guardianship procedures
  • Prohibition on participation in other research, apart from any other non-interventional research
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01329133

Contacts
Contact: Emmanuel CUNY, MD (0)5 56 79 55 77 ext +33 emmanuel.cuny@chu-bordeaux.fr
Contact: Olivier BRANCHARD, CRA (0)5 57 82 06 97 ext +33 olivier.branchard@chu-bordeaux.fr

Locations
France
Bordeaux University Hospital Recruiting
Bordeaux, France, 33000
Contact: Emmanuel CUNY, MD-PhD    (0)5 56 79 55 77 ext +33    emmanuel.cuny@chu-bordeaux.fr   
Principal Investigator: Emmanuel CUNY, MD-PhD         
Principal Investigator: Bruno AOUIZERATE, MD-PhD         
Sub-Investigator: Olivier DOUMY, MD         
Sub-Investigator: Jean-Yves ROTGE, MD         
Sub-Investigator: Dominique GUEHL, MD         
Sub-Investigator: François CAIRE, MD         
Clermont-Ferrand University Hospital Recruiting
Clermont-Ferrand, France, 63003
Contact: Pierre-Michel LLORCA, MD-PhD    (0)4 73 75 21 24 ext +33    pmllorca@chu-clermontferrand.fr   
Principal Investigator: Pierre-Michel LLORCA, MD-PhD         
Sub-Investigator: Isabelle CHEREAU-BOUDET, MD         
Sub-Investigator: Franck DURIF, MD         
Sub-Investigator: Ana-Raquel MARQUES, MD         
Sub-Investigator: Jean-Jacques LEMAIRE, MD         
Henri Mondor Hospital Not yet recruiting
Créteil, France, 94010
Contact: Stéphane PALFI, MD-PhD    (0)1 49 81 22 03 ext +33    stephane.palfi@hmn.aphp.fr   
Principal Investigator: Stéphane PALFI, MD-PhD         
Sub-Investigator: Jean-Marc GURRUCHAGA, MD         
Sub-Investigator: Gilles FENELON, MD         
Sub-Investigator: Bechir JARRAYA, MD         
Sub-Investigator: Bluenn QUILLEROU, MD         
Grenoble University Hospital Recruiting
Grenoble, France, 38043
Contact: Mircea POLOSAN, MD    (0)4 76 76 53 83 ext +33    MPolosan@chu-grenoble.fr   
Principal Investigator: Mircea POLOSAN, MD         
Sub-Investigator: Paul KRACK, MD         
Sub-Investigator: Stephan CHABARDES, MD         
Lille University Hospital Not yet recruiting
Lille, France, 59037
Contact: Serge BLOND, MD-PhD    (0)3 20 44 65 42 ext +33    sblond@chru-lille.fr   
Principal Investigator: Serge BLOND, MD-PhD         
Sub-Investigator: Maxime BUBROVSZKY, MD         
Sub-Investigator: Luc DEFEBVRE, MD         
Lyon University Hospital Not yet recruiting
Lyon, France, 69229
Contact: Mohamed SAOUD, MD-PhD    (0)4 72 11 80 64 ext +33    mohamed.saoud@chu-lyon.fr   
Principal Investigator: Mohamed SAOUD, MD-Phd         
Sub-Investigator: Emmanuel POULET, MD         
Sub-Investigator: Julien ECHE, MD         
Sub-Investigator: Stéphane THOBOIS, MD         
Sub-Investigator: Giullia SERRA, MD         
Sub-Investigator: Marc GUENOT, MD         
Marseille University Hospital Recruiting
Marseille, France, 13385
Contact: Christophe LANÇON, MD-PhD    (0)4 91 74 46 01 ext +33    Christophe.LANCON@ap-hm.fr   
Principal Investigator: Christophe LANÇON, MD-PhD         
Sub-Investigator: Jean FARISSE, MD         
Sub-Investigator: Claire FAJULA, MD         
Sub-Investigator: Alexandre EUSEBIO, MD         
Sub-Investigator: Tatiana WIDJAS, MD         
Sub-Investigator: Jean-Marie REGIS, MD         
Sub-Investigator: Marc LEVEQUE, MD         
Nice University Hospital Recruiting
Nice, France, 06202
Contact: Denys FONTAINE, MD    (0)4 92 03 85 28 ext +33    fontaine.d@chu-nice.fr   
Principal Investigator: Denys FONTAINE, MD         
Sub-Investigator: Bruno GIORDANA, MD         
Sub-Investigator: Michel BENOIT, MD         
Sub-Investigator: Michel BORG, MD         
Sainte-Anne Hospital Recruiting
Paris, France, 75674
Contact: Nicolas BAUP, MD    (0)1 45 21 22 02 ext +33    nicolas.baup@bct.aphp.fr   
Principal Investigator: Nicolas BAUP, MD         
Sub-Investigator: Marie-Odile KREBS, MD         
Sub-Investigator: Michael MANN, MD         
Sub-Investigator: Bertrand DEVAUX, MD         
Pitié-Salpêtrière Hospital Not yet recruiting
Paris, France, 75651
Contact: Luc MALLET, MD    (0)1 42 16 19 50 ext +33    luc.mallet@upmc.fr   
Principal Investigator: Luc MALLET, MD         
Sub-Investigator: Antoine PELISSOLO, MD         
Sub-Investigator: Jerome YELNIK, MD         
Sub-Investigator: Marie-Laure WELTER, MD         
Sub-Investigator: Philippe CORNU, MD         
Poitiers University Hospital Recruiting
Poitiers, France, 86021
Contact: Nemathollah JAAFARI, MD    (0)5 49 44 58 02 ext +33    nemat.jaafari@ch-poitiers.fr   
Principal Investigator: Nemathollah JAAFARI, MD         
Sub-Investigator: Jean-Luc HOUETO, MD         
Sub-Investigator: Benoit BATAILLE, MD         
Rennes University Hospital Not yet recruiting
Rennes, France, 35033
Contact: Bruno MILLET, MD-PhD    (0)2 99 33 39 37 ext +33    bruno.millet@univ-rennes1.fr   
Principal Investigator: Bruno MILLET, MD-PhD         
Sub-Investigator: Marc VERIN, MD         
Sub-Investigator: Claire HAEGELEN, MD         
Strasbourg University Hospital Recruiting
Strasbourg, France, 67091
Contact: Pierre KEHRLI, MD-PhD    (0)3 88 12 78 51 ext +33    pierre.kehrli@chru-strasbourg.fr   
Principal Investigator: Pierre KEHRLI, MD-PhD         
Sub-Investigator: Jean-Marie DANION, MD         
Sub-Investigator: Jack FOUCHER, MD         
Sub-Investigator: Jimmy VOIRIN, MD         
Sub-Investigator: Pascale BOUCHET, MD         
Toulouse University Hospital Not yet recruiting
Toulouse, France, 31059
Contact: Christophe ARBUS, MD    (0)5 61 55 75 10 ext +33    arbus.c@chu-toulouse.fr   
Principal Investigator: Christophe ARBUS, MD         
Sub-Investigator: Marion SIMONETTA-MOREAU, MD         
Sub-Investigator: Christine BREFEL-COURBON, MD         
Sub-Investigator: Fabienne ORY-MAGNE, MD         
Sub-Investigator: Olivier RASCOL, MD         
Sub-Investigator: Patrick CHAYNE, MD         
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
Study Chair: BENARD Antoine, MD University Hospital Bordeaux, France
Principal Investigator: Emmanuel CUNY, MD University Hospital Bordeaux, France
Principal Investigator: Bruno AOUIZERATE, MD-PhD Charles Perrens hospital, Bordeaux, France
  More Information

Publications:
Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT01329133     History of Changes
Other Study ID Numbers: CHUBX 2010/43
Study First Received: April 4, 2011
Last Updated: November 21, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
Deep brain stimulation (DBS)
Obsessive compulsive disorder
ventral striatum
subthalamic nucleus

Additional relevant MeSH terms:
Obsessive-Compulsive Disorder
Compulsive Personality Disorder
Anxiety Disorders
Mental Disorders
Personality Disorders

ClinicalTrials.gov processed this record on July 28, 2014