Radiosurgical Treatment for Obsessive-compulsive Disorder

This study has been terminated.
(Our Co sources were in a state of advanced decay. That prolonged our surgical procedures, making them inconveniently and perhaps dangerously long (> 12 hours))
Sponsor:
Collaborator:
Brown University
Information provided by (Responsible Party):
University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier:
NCT01004302
First received: October 28, 2009
Last updated: October 11, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Obsessive-compulsive Disorder
Procedure: ventral capsular/ventral striatal gamma capsulotomy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Ventral Capsular/Ventral Striatal Gamma Capsulotomy for Obsessive-compulsive Disorder: a Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by University of Sao Paulo General Hospital:

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 [ Time Frame: One year ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: July 2003
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sham Comparator: Sham surgery Procedure: ventral capsular/ventral striatal gamma capsulotomy
Comparison of active radiosurgical with sham radiosurgeries
Other Names:
  • Gamma ventral capsulotomy
  • Anterior capsulotomy
  • Gamma Knife radiosurgery
Active Comparator: Active radiosurgery Procedure: ventral capsular/ventral striatal gamma capsulotomy
Comparison of active radiosurgical with sham radiosurgeries
Other Names:
  • Gamma ventral capsulotomy
  • Anterior capsulotomy
  • Gamma Knife radiosurgery

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01004302

Locations
Brazil
Department and Institute of Psychiatry, General Hospital, University of São Paulo Medical School
São Paulo, SP, Brazil, 01060970
Sponsors and Collaborators
University of Sao Paulo General Hospital
Brown University
Investigators
Principal Investigator: Antonio C Lopes, MD, PhD Department and Institute of Psychiatry, General Hospital, University of São Paulo Medical School
  More Information

No publications provided by University of Sao Paulo General Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier: NCT01004302     History of Changes
Other Study ID Numbers: CAPPesq 521/02, CAPPesq 0968/05, CONEP 4891
Study First Received: October 28, 2009
Last Updated: October 11, 2012
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by University of Sao Paulo General Hospital:
Obsessive-compulsive disorder
Radiosurgery
Psychosurgery
Treatment outcome
Randomized Controlled Trials

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

ClinicalTrials.gov processed this record on October 21, 2014