Clinical trial NCT00640133: Effectiveness of Deep Brain Stimulation for Treating People With Treatment Resistant Obsessive-Compulsive Disorder
Official title: Controlled Trial of Deep Brain Stimulation for Obsessive-Compulsive Disorder
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Obsessive-Compulsive Disorder
Keywords: Deep Brain Stimulation
Treatment Refractory
Ventral Internal Capsule/Ventral Striatum
Neurosurgery
Neuroimaging
Lead sponsor: Butler Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2008-03-21
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Yale-Brown Obsessive-Compulsive Scale (YBOCS Severity Ratings)
timeFrame: YBOCS total score observed means at month-12
measure: Global Assessment of Functioning Scale (GAF)
timeFrame: GAF score observed means at month-12
measure: Social and Occupational Functioning Assessment Scale (SOFAS)
timeFrame: SOFAS score observed means at month-12 time point.
Secondary outcomes:
measure: Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ)
timeFrame: QLESQ total score observed means at month-12 time point.
measure: Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: MADRS total score observed means at month-12 time point.
measure: Hamilton Anxiety Rating Scale (HARS)
timeFrame: HARS total score observed means at month-12 time point.
measure: Behavioral Activation for Depression Scale (BADS)
timeFrame: Total BADS score observed means at month-12 time point.
measure: Hamilton Depression Rating Scale (HDRS)
timeFrame: Total HDRS score observed means at month-3 time point.
Other outcomes:
Locations:
city: Redwood City
country: United States
facility: Kaiser Permanente Redwood City Hospital
state: California
city: Washington
country: United States
facility: George Washington University Hospital
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
city: Providence
country: United States
facility: Butler Hospital
state: Rhode Island
Study officials:
affiliation: Butler Hospital/Brown University
name: Benjamin D. Greenberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders, (4th ed., text revision). Washington, DC: American Psychiatric Association.
citation: 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.