Electrical Stimulation of the Internal Capsule for Intractable Obsessive-compulsive Disorder (OCD)

Obsessive-Compulsive Disorder Clinical Trial

Official title:

Electrical Stimulation of the Internal Capsule for Intractable OCD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01061983
• Other study ID #: 000204
• Status: Completed
• Phase: Phase 2
• First received: February 2, 2010
• Last updated: February 21, 2013
• Start date: January 2001
• Est. completion date: October 2012

Study information

• Verified date: February 2013
• Source: Butler Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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. We also expect to determine how DBS affects brain activity in brain circuits strongly implicated in OCD, and how such effects may relate to symptom change. This treatment study therefore also permits a unique and crucial test of current neuroanatomical models of both OCD pathogenesis and mechanisms underlying the response to treatment.

Description:

Obsessive-compulsive disorder (OCD) is a chronic and debilitating illness that affects between 2% and 3% of the adult population of 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 se 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 efficacy of DBS in treating people with severe and treatment-resistant OCD.

Study participation through follow-up will last up to 2 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 series of initial tests and examinations that will include psychiatric, medical, and neuropsychological histories and examinations.

Implantation of the devices will be performed at a single session. The leads that are inserted into the anterior limb of each internal capsule, will be implanted under local anesthesia. On the day of the surgery, participants will have a metal frame fixed to their heads for support during surgery, and magnetic resonance imagining (MRI) will be used to determine the exact placement of the wires. An extension wire will pass from the scalp area to the subclavicular region and connect each electrode to a subcutaneous implanted pulse generator (IPG), which will be implanted under general anesthesia. After placement of the DBS system, the patient will be admitted to the hospital for overnight observation for possible complications. Postoperative evaluation will consist of physical and neurological examinations, postoperative CBC, electrolyte panel, x-rays of the head, neck, and chest, a standard shunt series to ensure the integrity of connections, and a head CT scan to monitor for possible postoperative intracranial hemorrhage.

Surgical implantation will be followed by a three-week period with no stimulation, and then an intensive five-day preliminary outpatient stimulation trial, followed by longer-term outpatient stimulation. All patients will follow the same sequence of test conditions. The initial DBS testing will be open, followed by three blocks of testing in which the patients and investigators administering rating scales will not be informed of the stimulation condition. These three blocks will in general be three months long, but may be longer or shorter depending on the stability of any clinical improvement, and the possible emergence of symptom worsening. The remainder of the the study, up to the two-year study endpoint, will consist of a continuation phase of active open stimulation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: October 2012
• Est. primary completion date: April 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• OCD, diagnosed by Structural Clinical Interview for DSM-IV (SCID-IV), judged to be of disabling severity with a Yale-Brown Obsessive-Compulsive Scale (YBOCS) score of 28 and a Global Assessment of Function (GAF) score of 45 or less.

• Persistence of this level of impairment for a minimum of five years despite adequate trials of or intolerance to 3 or 4 selective serotonin transporter inhibitors including fluoxetine, sertraline, fluvoxamine, paroxetine and clomipramine alone and in combination with behavior therapy, and augmentation of one of the selective SRIs with clomipramine, a neuroleptic, and clonazepam.

• Age of at least eighteen years, and no more than 55 years.

• Able to understand and comply with instructions.

• Written informed consent.

• Either drug free or on a stable drug regime for at least 6 weeks.

• Good general health.

Exclusion Criteria:

• Current or past psychotic disorder.

• Any clinically significant neurological disorder or medical illness affecting brain function, other than motor tics or Gilles de la Tourette syndrome.

• Any clinically significant abnormality on preoperative magnetic resonance imaging (MRI).

• Any surgical contraindications to undergoing DBS, including labeled contraindications for DBS and/or inability to undergo presurgical MRI (cardiac pacemaker, pregnancy, metal in body, severe claustrophobia), infection, coagulopathy, inability to undergo awake operation, significant cardiac or other medical risk factors for surgery.

• Current or unstably remitted substance abuse disorder.

• Pregnancy and women of childbearing age not using effective contraception.

• History of body dysmorphic disorder.

• History of severe personality disorder.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Compulsive Behavior
• Obsessive-Compulsive Disorder

Intervention

Device:
• Medtronic Activa Deep Brain Stimulation
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.

Locations

Country	Name	City	State
United States	Butler Hospital	Providence	Rhode Island

Sponsors (2)

Lead Sponsor	Collaborator
Butler Hospital	Medtronic

Country where clinical trial is conducted

United States, 

References & Publications (3)

Greenberg BD, Gabriels LA, Malone DA Jr, Rezai AR, Friehs GM, Okun MS, Shapira NA, Foote KD, Cosyns PR, Kubu CS, Malloy PF, Salloway SP, Giftakis JE, Rise MT, Machado AG, Baker KB, Stypulkowski PH, Goodman WK, Rasmussen SA, Nuttin BJ. Deep brain stimulati — View 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):23 — View Citation

Rauch SL, Dougherty DD, Malone D, Rezai A, Friehs G, Fischman AJ, Alpert NM, Haber SN, Stypulkowski PH, Rise MT, Rasmussen SA, Greenberg BD. A functional neuroimaging investigation of deep brain stimulation in patients with obsessive-compulsive disorder. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Obsessive-compulsive disorder (OCD) severity (Yale-Brown Obsessive-Compulsive Scale)		Measured at baseline, then monthly for nine months, then every three months during the open continuation phase	No
Secondary	Depression severity (Hamilton Depression Scale), Anxiety (Hamilton Anxiety Scale), and neuropsychological battery.		At baseline, monthly for 9 months, then every 3 months for the continuation of the open phase.	No