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

NCT ID: NCT00640133

Last Updated: 2024-07-29

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2024-12-01

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.

Detailed Description

Obsessive-compulsive disorder (OCD) is a chronic and debilitating illness that affects between 2% and 3% of adults in the United States. People with OCD often experience persistent unwanted thoughts and carry out ritual-like behaviors to rid themselves of these obsessive thoughts. Additionally, OCD symptoms are usually tied with feelings of intense anxiety and functional impairment, making it important for people with OCD to seek effective treatment. Although there are currently many treatment options for OCD, including psychotherapy and medications such as serotonin reuptake inhibitors, between 40% and 60% of people with OCD only partially respond or do not respond at all to these treatment methods. Given the large percentage of people who do not respond to aggressive conventional treatments, alternative options are necessary for people with treatment-resistant OCD. Deep brain stimulation (DBS) is a procedure that involves the use of thin wires to carry electric current to parts of the brain associated with producing OCD symptoms. DBS has been effectively and safely used to treat movement disorders, such as Parkinson's disease, and may be beneficial in reducing OCD symptom severity. This study will evaluate the safety and effectiveness of DBS in treating people with severe and otherwise treatment-resistant OCD.

Study participation through follow-up will last 4 years. Participants will be allowed to remain on any pre-surgical medications or behavioral therapy programs throughout the study. Before surgery, all participants will undergo a 3- to 4-day series of initial tests and examinations that will include a physical and neurological examination; blood and urine screening tests; an electrocardiogram (EKG); an electroencephalography (EEG); and detailed psychological testing, including tests of perception, learning, and memory. The EEGs may be performed again after surgery to measure potential changes in brain electrical activity due to DBS.

On the day of the surgery, participants will take a low dose of anxiety medication, have a metal frame fixed to their heads for support during surgery, and undergo a magnetic resonance imaging (MRI) scan to determine where to place the stimulating wires. After being injected with a local anesthetic, participants will undergo the first part of the operation, which will involve the implantation of neurostimulators in the ventral caudate/ventral striatum brain region. For the second part of the operation, after participants are administered general anesthesia, they will have the implantable neurostimulators (INSs) placed in their chests and the connecting wires to the brain placed under their skin. The entire surgical procedure will take 3 to 4 hours, with a 1- to 2-day post-operative hospital stay for recovery. During the post-operative stay, participants will undergo x-rays and a computed tomography (CT) scan of the head.

Two to 3 weeks after surgery, participants will be divided randomly into either a group that receives DBS immediately or a group that first receives sham DBS and then active DBS after 3 months. The level of stimulation will be adjusted individually and on the basis of each participant's response to the stimulation. Participants will complete rating forms, a clinical evaluation, and a check of the stimulators every month for the first 3 months, then at least every 3 months for the rest of the year, and then every 6 months for the remaining years of the study. On the Year 1 visit, participants will repeat the baseline detailed psychological testing. Periodically throughout the 4-year study, staff will contact participants by phone to ask about OCD symptoms, mood, anxiety, and possible side effects. Also throughout the study, participants will need to have the INSs replaced every 5 to 16 months on average.

Participants will also be invited to participate in a related study that involves positron emission tomography (PET) scanning to determine how the stimulation changes activity in the brain. Participation in the separate PET study is optional and will not affect current study participation.

Conditions

Obsessive-Compulsive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Active DBS

Participants will receive deep brain stimulation.

Group Type: ACTIVE_COMPARATOR

Active DBS

Intervention Type: 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.

Sham DBS

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

Group Type: SHAM_COMPARATOR

Active DBS

Intervention Type: 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.

Sham DBS

Intervention Type: 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.

Interventions

Active DBS

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.

Intervention Type: DEVICE

Sham DBS

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.

Intervention Type: DEVICE

Other Intervention Names

Activa Deep Brain Stimulation System (Medtronic, Inc.); Implantable Neurostimulator (INS); Activa Deep Brain Stimulation System (Medtronic, Inc.); Implantable Neurostimulator (INS)

Eligibility Criteria

Inclusion Criteria

• 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:

1. 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;

2. augmentation of one of the selective serotonin transporter inhibitors with clomipramine, and a neuroleptic (each for at least 2 weeks); and

3. 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Butler Hospital

OTHER

Sponsor Role: lead

Responsible Party

Dr. Benjamin Greenberg

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Benjamin D. Greenberg, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Butler Hospital/Brown University

Locations

Kaiser Permanente Redwood City Hospital

Redwood City, California, United States

George Washington University Hospital

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

University of Florida

Gainesville, Florida, United States

University of Chicago

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

The Cleveland Clinic

Cleveland, Ohio, United States

Butler Hospital

Providence, Rhode Island, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 16855529 (View on PubMed)

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.

Reference Type: RESULT

PMID: 2684084 (View on PubMed)

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.

Reference Type: RESULT

PMID: 8290681 (View on PubMed)

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.

Reference Type: RESULT

PMID: 444788 (View on PubMed)

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.

Reference Type: 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.

Reference Type: RESULT

PMID: 13638508 (View on PubMed)

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.

Reference Type: RESULT

PMID: 14399272 (View on PubMed)

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

Reference Type: 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.

Reference Type: DERIVED

PMID: 23128051 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U01MH076179

Identifier Type: NIH

Identifier Source: secondary_id

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DSIR 83-ATSO

Identifier Type: -

Identifier Source: secondary_id

U01MH076179

Identifier Type: NIH

Identifier Source: org_study_id

View Link