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Radiosurgical Treatment for Obsessive-compulsive Disorder

Primary Purpose

Obsessive-compulsive Disorder

Status
Terminated
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
ventral capsular/ventral striatal gamma capsulotomy
Sponsored by
University of Sao Paulo General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obsessive-compulsive Disorder focused on measuring Obsessive-compulsive disorder, Radiosurgery, Psychosurgery, Treatment outcome, Randomized Controlled Trials

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • A DSM-IV diagnosis of OCD as the main diagnostic entity. If comorbid axis I or II disorders are present, OCD symptoms are the most troublesome among disorders.
  • Age range between 18 and 60 years old.
  • At least 5 years of OCD symptoms.
  • "Yale-Brown Obsessive-Compulsive Scale" (YBOCS) scores greater than 26 (or greater than 13, for isolated obsessions or compulsions).
  • Refractoriness criteria fulfilled.
  • To be accepted by the "best estimate" method as a treatment refractory patient. It consists in the careful examination of each patient's history by two OCD specialists, so as to confirm refractoriness status.

Refractoriness criteria:

  • At least 3 serotonin reuptake inhibitors have been tried before (selective or not). One of these trials must have included clomipramine. All drugs were used for a minimum of 12 weeks, at the maximum doses or the maximally tolerated doses.
  • Previous participation in a cognitive behavior therapy program (exposure and response prevention), for a minimum of 20 hours' time; or participation for some time, without subsequent adherence, due to severe OCD symptoms, and acceptance of the independent review board.
  • YBOCS scores reductions after adequate drug therapy and psychotherapy not better than 25 %, or confirmation of no clinical improvements by the mental health professionals who were responsible for the treatments of the patient.
  • By the end of adequately conducted pharmacological trials, "Clinical Global Impression" (CGI) scores not better than minimal improvement.
  • Previous use of at least two antidepressant augmentation strategies (such as the association of a typical or atypical antipsychotic, another serotonin reuptake inhibitor, a benzodiazepine, lithium carbonate, or buspirone), in adequate doses for a sufficient period of time, without satisfactory responses.

Exclusion Criteria:

  • Less than 18 years or more than 60 years of age.
  • Past history of head injury, with posttraumatic amnesia.
  • Past or general medical condition, or neurological illness with brain compromise (severe and in active phase)
  • History of physiological effects of a substance, as determinant of psychopathological symptoms, or cumulative signs of alcohol or drug abuse in the Central Nervous System (such cortical atrophy), confirmed by a neuroimaging scan.
  • Pregnancy or lactation.
  • Refusal to participate in radiosurgical procedures.
  • Refusal to sign the Patient Information and Consent Form, or refusal to take part in this study.
  • History of mental retardation and/or being unable to understand the Patient Information and Consent Form, confirmed by poor performance on neuropsychological tests.

Sites / Locations

  • Department and Institute of Psychiatry, General Hospital, University of São Paulo Medical School

Arms of the Study

Arm 1

Arm 2

Arm Type

Sham Comparator

Active Comparator

Arm Label

Sham surgery

Active radiosurgery

Arm Description

Outcomes

Primary Outcome Measures

A reduction of at least 35 % in the Yale-Brown Obsessive Compulsive Scale (YBOCS) scores and an "improved" or "much improved" score on the Clinical Global Impression (CGI) scale

Secondary Outcome Measures

Full Information

First Posted
October 28, 2009
Last Updated
October 11, 2012
Sponsor
University of Sao Paulo General Hospital
Collaborators
Brown University
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1. Study Identification

Unique Protocol Identification Number
NCT01004302
Brief Title
Radiosurgical Treatment for Obsessive-compulsive Disorder
Official Title
Ventral Capsular/Ventral Striatal Gamma Capsulotomy for Obsessive-compulsive Disorder: a Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Terminated
Why Stopped
Our Co sources were in a state of advanced decay. That prolonged our surgical procedures, making them inconveniently and perhaps dangerously long (> 12 hours)
Study Start Date
July 2003 (undefined)
Primary Completion Date
January 2013 (Anticipated)
Study Completion Date
January 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Sao Paulo General Hospital
Collaborators
Brown University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Up to 40% of Obsessive-Compulsive Disorder (OCD) patients do not respond to conventional treatments (medications or behavior therapy). For some of them, a neurosurgical treatment can be indicated. Among various surgical techniques, Gamma Knife radiosurgery has the advantage of not requiring the production of burr hole openings in the skull. However, there are no randomized controlled trials of radiosurgical procedures. The investigators' aim is to investigate whether radiosurgery for the treatment of severe and refractory OCD is efficacious and safe, by a double-blind, randomized controlled trial. Forty-eight refractory OCD patients will be randomized into two different groups: the first one will receive standard radiosurgery; the second group will be submitted to a false radiosurgery ("sham operation"). Patients who had been previously submitted to sham surgery will be able to undergo real operations after one year of follow-up, when blinding is broken. For a minimum period of one year, patients will be periodically followed-up in terms of psychiatric changes (including OCD symptoms), global functioning, cognitive/personality changes and neuroimaging findings.
Detailed Description
Various studies have demonstrated that good treatment responses in Obsessive Compulsive Disorder (OCD) are often obtained in 60 to 80 % of patients, whether employing serotonin reuptake inhibitors or behavior therapy. However, a subgroup of OCD patients are refractory to the classical therapeutic options, even after maximum dosage regimens and sufficiently long treatment follow-ups are devised. Severe psychosocial and occupational impairments are meanwhile observable. These subjects are often referred to stereotactic neurosurgeries. Among the various surgical techniques, a radiosurgical modality (double-shot ventral capsular/ventral striatal - VC/VS gamma capsulotomy, or simply double-shot gamma ventral capsulotomy) has been recently developed. On the other hand, there are no randomized controlled trials of Gamma Knife radiosurgeries in Psychiatry. The aim of this study is to investigate whether double-shot VC/VS gamma capsulotomy is efficacious and to describe its adverse events/complications profiles, in a double-blind, randomized controlled trial of this radiosurgical technique for the treatment of refractory OCD. Forty-eight refractory OCD patients will be randomized into two different groups: the first one will receive standard radiosurgery; the second group will be submitted to a false radiosurgical intervention ("sham operation"). All subjects will be previously assessed by a preliminary clinical/psychiatric interview, as well as by extensive specific instruments regarding psychiatric diagnosis, OCD evolution and severity, anxiety/depression symptoms, tics expression, psychosocial impairment, personality changes, etc. A neuropsychological tests battery will also be employed. All patients will be offered a periodical follow-up, during which assessment scales and neuroimaging exams (magnetic resonance imaging) will be repeated. Patients who had been previously submitted to placebo surgery will be able to undergo real operations after the one-year follow-up period, when blinding is broken. Scores results will be analyzed among the groups, as well as adverse events profiles, cognitive/personality changes, clinical global functioning and neuroimaging findings. Improvements in Yale-Brown Obsessive Compulsive Scale (YBOCS) and Clinical Global Impression (CGI) scores will be taken as the primary treatment response criteria.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obsessive-compulsive Disorder
Keywords
Obsessive-compulsive disorder, Radiosurgery, Psychosurgery, Treatment outcome, Randomized Controlled Trials

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sham surgery
Arm Type
Sham Comparator
Arm Title
Active radiosurgery
Arm Type
Active Comparator
Intervention Type
Procedure
Intervention Name(s)
ventral capsular/ventral striatal gamma capsulotomy
Other Intervention Name(s)
Gamma ventral capsulotomy, Anterior capsulotomy, Gamma Knife radiosurgery
Intervention Description
Comparison of active radiosurgical with sham radiosurgeries
Primary Outcome Measure Information:
Title
A reduction of at least 35 % in the Yale-Brown Obsessive Compulsive Scale (YBOCS) scores and an "improved" or "much improved" score on the Clinical Global Impression (CGI) scale
Time Frame
One year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: A DSM-IV diagnosis of OCD as the main diagnostic entity. If comorbid axis I or II disorders are present, OCD symptoms are the most troublesome among disorders. Age range between 18 and 60 years old. At least 5 years of OCD symptoms. "Yale-Brown Obsessive-Compulsive Scale" (YBOCS) scores greater than 26 (or greater than 13, for isolated obsessions or compulsions). Refractoriness criteria fulfilled. To be accepted by the "best estimate" method as a treatment refractory patient. It consists in the careful examination of each patient's history by two OCD specialists, so as to confirm refractoriness status. Refractoriness criteria: At least 3 serotonin reuptake inhibitors have been tried before (selective or not). One of these trials must have included clomipramine. All drugs were used for a minimum of 12 weeks, at the maximum doses or the maximally tolerated doses. Previous participation in a cognitive behavior therapy program (exposure and response prevention), for a minimum of 20 hours' time; or participation for some time, without subsequent adherence, due to severe OCD symptoms, and acceptance of the independent review board. YBOCS scores reductions after adequate drug therapy and psychotherapy not better than 25 %, or confirmation of no clinical improvements by the mental health professionals who were responsible for the treatments of the patient. By the end of adequately conducted pharmacological trials, "Clinical Global Impression" (CGI) scores not better than minimal improvement. Previous use of at least two antidepressant augmentation strategies (such as the association of a typical or atypical antipsychotic, another serotonin reuptake inhibitor, a benzodiazepine, lithium carbonate, or buspirone), in adequate doses for a sufficient period of time, without satisfactory responses. Exclusion Criteria: Less than 18 years or more than 60 years of age. Past history of head injury, with posttraumatic amnesia. Past or general medical condition, or neurological illness with brain compromise (severe and in active phase) History of physiological effects of a substance, as determinant of psychopathological symptoms, or cumulative signs of alcohol or drug abuse in the Central Nervous System (such cortical atrophy), confirmed by a neuroimaging scan. Pregnancy or lactation. Refusal to participate in radiosurgical procedures. Refusal to sign the Patient Information and Consent Form, or refusal to take part in this study. History of mental retardation and/or being unable to understand the Patient Information and Consent Form, confirmed by poor performance on neuropsychological tests.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio C Lopes, MD, PhD
Organizational Affiliation
Department and Institute of Psychiatry, General Hospital, University of São Paulo Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department and Institute of Psychiatry, General Hospital, University of São Paulo Medical School
City
São Paulo
State/Province
SP
ZIP/Postal Code
01060970
Country
Brazil

12. IPD Sharing Statement

Citations:
PubMed Identifier
25645373
Citation
Batistuzzo MC, Hoexter MQ, Taub A, Gentil AF, Cesar RC, Joaquim MA, D'Alcante CC, McLaughlin NC, Canteras MM, Shavitt RG, Savage CR, Greenberg BD, Noren G, Miguel EC, Lopes AC. Visuospatial Memory Improvement after Gamma Ventral Capsulotomy in Treatment Refractory Obsessive-Compulsive Disorder Patients. Neuropsychopharmacology. 2015 Jul;40(8):1837-45. doi: 10.1038/npp.2015.33. Epub 2015 Feb 3.
Results Reference
derived
PubMed Identifier
25054836
Citation
Lopes AC, Greenberg BD, Canteras MM, Batistuzzo MC, Hoexter MQ, Gentil AF, Pereira CA, Joaquim MA, de Mathis ME, D'Alcante CC, Taub A, de Castro DG, Tokeshi L, Sampaio LA, Leite CC, Shavitt RG, Diniz JB, Busatto G, Noren G, Rasmussen SA, Miguel EC. Gamma ventral capsulotomy for obsessive-compulsive disorder: a randomized clinical trial. JAMA Psychiatry. 2014 Sep;71(9):1066-76. doi: 10.1001/jamapsychiatry.2014.1193.
Results Reference
derived

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Radiosurgical Treatment for Obsessive-compulsive Disorder

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