Effectiveness of Deep Brain Stimulation for Treating People With Treatment Resistant Obsessive-Compulsive Disorder

NCT00640133 | Active Not Recruiting Phase 4 Results DMC

• 2 other identifiers: U01MH076179DSIR 83-ATSO
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 9

Brief Summary

This study will evaluate the safety and effectiveness of deep brain stimulation in treating people with severe and otherwise treatment-resistant obsessive-compulsive disorder.

Conditions

Obsessive-Compulsive Disorder

Keywords

Deep Brain Stimulation; Treatment Refractory; Ventral Internal Capsule/Ventral Striatum; Neurosurgery; Neuroimaging

Outcome Measures

Primary Outcomes (3)

• Yale-Brown Obsessive-Compulsive Scale (YBOCS Severity Ratings)

  The Yale-Brown Obsessive-Compulsive Scale (YBOCS) is a 10 question evaluator-administered measure assessing the severity of obsessions and compulsions over the past week. Obsession and compulsion severity are evaluated separately (ratings from 0-20 for each category) with total scores ranging from 0-40. Higher scores for obsessions, compulsions and total score indicate more severe symptoms over the past week.

  YBOCS total score observed means at month-12

• Global Assessment of Functioning Scale (GAF)

  A numeric scale (0 through 100) used to rate the social, occupational, and psychological overall functioning during the week of poorest functioning in the past month. Higher scores indicate a higher level of functioning, while low scores indicate impaired global functioning.

  GAF score observed means at month-12

• Social and Occupational Functioning Assessment Scale (SOFAS)

  A numeric scale (0 through 100) used to rate the social, occupational, and psychological functioning during the week of poorest functioning in the past month. Higher scores indicate higher levels of social and occupational functioning, while low scores represent social and occupational impairment.

  SOFAS score observed means at month-12 time point.

Secondary Outcomes (5)

• Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ)

  QLESQ total score observed means at month-12 time point.

• Montgomery-Asberg Depression Rating Scale (MADRS)

  MADRS total score observed means at month-12 time point.

• Hamilton Anxiety Rating Scale (HARS)

  HARS total score observed means at month-12 time point.

• Behavioral Activation for Depression Scale (BADS)

  Total BADS score observed means at month-12 time point.

• Hamilton Depression Rating Scale (HDRS)

  Total HDRS score observed means at month-3 time point.

Study Arms (2)

Active DBS

ACTIVE COMPARATOR

Participants will receive deep brain stimulation.

Device: Active DBS

Sham DBS

SHAM COMPARATOR

Participants will receive sham deep brain stimulation for several months and then active deep brain stimulation thereafter.

Device: Active DBS; Device: Sham DBS

Interventions

Active DBS DEVICE

In DBS, thin wires are used to carry electric current to the parts of the brain involved in OCD symptoms. These wires are implanted surgically and are attached to battery operated stimulators usually implanted in the chest. The study doctor will adjust the settings of the electrical stimulation to optimize treatment for each participant. After a post-operative rest, participants will receive immediate DBS treatment throughout.

Also known as: Activa Deep Brain Stimulation System (Medtronic, Inc.), Implantable Neurostimulator (INS)

Active DBS; Sham DBS

Sham DBS DEVICE

In DBS, thin wires are used to carry electric current to the parts of the brain involved in OCD symptoms. These wires are implanted surgically and are attached to battery operated stimulators usually implanted in the chest. The study doctor will mimic adjusting the settings of the electrical stimulation. After a post-operative rest, participants will receive DBS treatment after a delay of several months. Afterwards, all participants will receive open-label long-term DBS.

Also known as: Activa Deep Brain Stimulation System (Medtronic, Inc.), Implantable Neurostimulator (INS)

Sham DBS

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Obsessive-compulsive disorder (OCD), diagnosed by Structured Clinical Interview for DSM-IV (SCID-IV)
• Presence of disabling severity, as assessed by a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of at least 30
• Impaired functioning, indicated by a Global Assessment of Functioning (GAF) score of 45 or less
• Documented highly treatment refractory illness; the documentation must demonstrate persistence of severe symptoms and impairment for 5 or more years despite at least three first-line and two second-line treatments, as follows:
• at least three adequate trials of, or documented intolerance to, different serotonin transporter inhibitors (e.g., fluoxetine, sertraline, fluvoxamine, paroxetine, citalopram, escitalopram, clomipramine) for at least 3 months at the maximum tolerated dose. These trials may include any of the agents above, but must include an adequate course of clomipramine, either alone or in combination with a more selective serotonin transporter inhibitor;
• augmentation of one of the selective serotonin transporter inhibitors with clomipramine, and a neuroleptic (each for at least 2 weeks); and
• adequate behavior therapy (more than 20 sessions of exposure and response prevention by a therapist with substantial expertise in OCD treatment as determined by the investigators) with at least one of these trials and tried in combination with medication therapy
• Either drug free or on a stable drug regimen for at least 6 weeks before study entry
• General good overall health
• If possible, has a family member or significant other who sees the participant regularly, can communicate with the study team as needed, and, if necessary, can attend study visits
• Local referring psychiatrist willing to provide ongoing care during and after the trial, to work closely with the research team, and to agree that the study psychiatrist will prescribe medications during the 3-month masked phase
• Platelet count greater than 125,000 per cubic millimeter and a prothrombin time and partial thromboplastin time within normal limits

You may not qualify if:

• Current or past psychotic disorder
• Full-scale IQ below 75 on the Wechsler Abbreviated Scale of Intelligence (WASI), or cognitive impairment that would affect a participant's ability to give informed consent or provide interview or self-report data reliably, as determined by the Consent Monitor and the site psychiatrist.
• A clinical history of bipolar mood disorder
• Any current clinically significant neurological disorder or medical illness affecting brain function, other than a tic disorder
• Any clinically significant abnormality on preoperative MRI
• Any labeled DBS contraindication, inability to undergo presurgical MRI (e.g., cardiac pacemaker, pregnancy, metal in body, severe claustrophobia), infection, coagulopathy, inability to undergo an awake operation, significant cardiac risk factors, or other medical risk factors for surgery
• Current or unstable remitted substance abuse or dependence
• Positive urine toxicology screen for substance abuse
• Pregnant and/or woman of childbearing age not using effective forms of birth control
• Clinical history of severe personality disorder
• An inability to control suicide attempts, imminent risk of suicide in the investigator's judgment, or a history of serious suicidal behavior, which is defined using the Columbia-Suicide Severity Rating Scale (C-SSRS) as either (1) one or more actual suicide attempts in the 3 years before study entry with the lethality rated at 3 or higher, or (2) one or more interrupted suicide attempts with a potential lethality judged to result in serious injury or death
• Current diagnosis of body dysmorphic disorder
• Evidence of dementia of other significant cognitive impairment on neuropsychological evaluation

Sponsors & Collaborators

• Butler Hospital: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (9)

Kaiser Permanente Redwood City Hospital

Redwood City, California, 94063, United States

Location

George Washington University Hospital

Washington D.C., District of Columbia, 20037, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

The Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Butler Hospital

Providence, Rhode Island, 02906, United States

Location

Related Publications (9)

• Greenberg BD, Malone DA, Friehs GM, Rezai AR, Kubu CS, Malloy PF, Salloway SP, Okun MS, Goodman WK, Rasmussen SA. Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology. 2006 Nov;31(11):2384-93. doi: 10.1038/sj.npp.1301165. Epub 2006 Jul 19.

  PMID: 16855529 BACKGROUND

• Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, Heninger GR, Charney DS. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry. 1989 Nov;46(11):1006-11. doi: 10.1001/archpsyc.1989.01810110048007.

  PMID: 2684084 RESULT

• Endicott J, Nee J, Harrison W, Blumenthal R. Quality of Life Enjoyment and Satisfaction Questionnaire: a new measure. Psychopharmacol Bull. 1993;29(2):321-6.

  PMID: 8290681 RESULT

• Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382-9. doi: 10.1192/bjp.134.4.382.

  PMID: 444788 RESULT

• Kanter, J. W., Rusch, L. C., Busch, A. M., & Sedivy, S. K. (2009). Validation of the behavioral activation for depression scale (BADS) in a community sample with elevated depressive symptoms. Journal of Psychopathology and Behavioral Assessment, 31, 36-42.

  RESULT

• HAMILTON M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50-5. doi: 10.1111/j.2044-8341.1959.tb00467.x. No abstract available.

  PMID: 13638508 RESULT

• HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23(1):56-62. doi: 10.1136/jnnp.23.1.56. No abstract available.

  PMID: 14399272 RESULT

• American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders, (4th ed., text revision). Washington, DC: American Psychiatric Association.

  RESULT

• McLaughlin NC, Didie ER, Machado AG, Haber SN, Eskandar EN, Greenberg BD. Improvements in anorexia symptoms after deep brain stimulation for intractable obsessive-compulsive disorder. Biol Psychiatry. 2013 May 1;73(9):e29-31. doi: 10.1016/j.biopsych.2012.09.015. Epub 2012 Nov 3. No abstract available.

  PMID: 23128051 DERIVED

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Implantable Neurostimulators

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electrodes, Implanted; Electrodes; Electrical Equipment and Supplies; Equipment and Supplies; Prostheses and Implants

Results Point of Contact

• Title: Dr. Benjamin Greenberg
• Organization: Butler Hospital

be3ngreenb@gmail.com

(401) 455-6602

Study Officials

• Benjamin D. Greenberg, MD, PhD

  Butler Hospital/Brown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 17, 2008
• First Posted: March 21, 2008
• Study Start: March 1, 2008
• Primary Completion: May 24, 2018
• Study Completion: December 1, 2024
• Last Updated: July 29, 2024
• Results First Posted: October 11, 2019

Record last verified: 2024-07

Locations

US (9)