Radiosurgical Treatment for Obsessive-compulsive Disorder

Obsessive-compulsive Disorder Clinical Trial

Official title:

Ventral Capsular/Ventral Striatal Gamma Capsulotomy for Obsessive-compulsive Disorder: a Randomized Controlled Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01004302
• Other study ID #: CAPPesq 521/02
• Secondary ID: CAPPesq 0968/05C
• Status: Terminated
• Phase: Phase 2
• First received: October 28, 2009
• Last updated: October 11, 2012
• Start date: July 2003
• Est. completion date: January 2015

Study information

• Verified date: October 2012
• Source: University of Sao Paulo General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: January 2015
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Compulsive Behavior
• Obsessive-Compulsive Disorder

Intervention

Procedure:
• ventral capsular/ventral striatal gamma capsulotomy
Comparison of active radiosurgical with sham radiosurgeries

Locations

Country	Name	City	State
Brazil	Department and Institute of Psychiatry, General Hospital, University of São Paulo Medical School	São Paulo	SP

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital	Brown University

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		One year	No