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Deep Brain Stimulation for the Treatment of Refractory Anorexia Nervosa

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01476540
Recruitment Status : Completed
First Posted : November 22, 2011
Last Update Posted : October 30, 2019
Sponsor:
Information provided by (Responsible Party):
Andres M. Lozano, University Health Network, Toronto

Tracking Information
First Submitted Date  ICMJE November 15, 2011
First Posted Date  ICMJE November 22, 2011
Last Update Posted Date October 30, 2019
Study Start Date  ICMJE July 2011
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 28, 2019)
Eating Disorder Related Preoccupations and Rituals [ Time Frame: Change from baseline in Eating Disorder Related Preoccupations and Rituals scores at 3 months, 6 months and 12 months ]
Eating Disorder Related Preoccupations and Rituals scores
Original Primary Outcome Measures  ICMJE
 (submitted: November 17, 2011)
Eating Disorder Related Preoccupations and Rituals [ Time Frame: Change from baseline in Eating Disorder Related Preoccupations and Rituals scores at 3 months, 6 months and 12 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2019)
  • Depression [ Time Frame: Change from baseline in depression scores at 3 months, 6 months and 12 months ]
    Hamilton Depression Rating Scale (HAMD), Beck Depression Inventory (BDI)
  • Anxiety [ Time Frame: Change from baseline in anxiety scores at 3 months, 6 months and 12 months ]
    Beck Anxiety Inventory (BAI)
  • Quality of Life questionnaire score through change from baseline compared to post-implant visit [ Time Frame: Change from baseline in Quality of Life scores at 3 months, 6 months and 12 months ]
    Health Survey Short Form (SF36), Quality of Life Scale
Original Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2011)
  • Depression [ Time Frame: Change from baseline in depression scores at 3 months, 6 months and 12 months ]
    Hamilton Depression Rating Scale (HAMD), Beck Depression Inventory (BDI)
  • Anxiety [ Time Frame: Change from baseline in anxiety scores at 3 months, 6 months and 12 months ]
    Beck Anxiety Inventory (BAI)
  • Quality of Life [ Time Frame: Change from baseline in Quality of Life scores at 3 months, 6 months and 12 months ]
    Health Survey Short Form (SF36), Quality of Life Scale
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Deep Brain Stimulation for the Treatment of Refractory Anorexia Nervosa
Official Title  ICMJE Deep Brain Stimulation for the Treatment of Refractory Anorexia Nervosa
Brief Summary Anorexia Nervosa (AN) is a challenging, chronic, refractory illness with the highest mortality rate of any psychiatric condition. Advances in the neuroimaging, genetics and neurobiology of AN has led to a greater understanding of its underlying pathophysiology, although few significant advances in treatment have been made in the last half-century. The central features of AN, which include an intense fear of gaining weight, a refusal to maintain a normal weight, as well as significant anxiety, anhedonia and dysphoria surrounding food, have been linked to dysfunction in key brain structures and circuits. Deep Brain Stimulation (DBS) is a neurosurgical procedure that involves the insertion of electrodes into structures believed to drive pathological behavior. The procedure is approved for the management of movement disorders, such as Parkinson's Disease, and has shown promising early results in the management of some psychiatric conditions, such as Major Depression. The purpose of this study is to explore the safety and initial efficacy of DBS, in patients with treatment resistant AN.
Detailed Description

Anorexia nervosa is a chronic, and debilitating psychiatric disorder associated with the highest mortality rate of any psychiatric condition. Despite advances in neuroimaging, genetics, pharmacology and psychosocial interventions in the last half century, little progress have been made in altering the natural history of the condition or its outcomes. It has further become increasingly accepted that the thoughts and behaviors at the root of AN derive from dysfunctional neuroanatomic circuits, whose activity and deviations can be detected with sophisticated neuroimaging techniques. Much progress has also been made in mapping the psychology of the illness to underlying neuroanatomic and neurophysiologic processes that drive and maintain these behaviors, even in the face of severe starvation and impending death. Dysfunctional reward processing, compulsive hyperactivity, chronic anxiety and depression, all suggest that AN shares much in common with other conditions, such as OCD, for which surgical therapy has been tried, and met with success.

Deep Brain Stimulation is a neurosurgical tool that has been widely used for over twenty years. Most of the experience with DBS comes from the movement disorder literature where significant success has been had with the management of disabling Parkinson's disease (PD) and dystonia. The most experience so far has been in Parkinson's disease where well over 50,000 patients globally have received the operation. DBS is believed to work by using small amounts of electricity to disrupt the activity of brain structures that produce troublesome symptoms. DBS has also been used in psychiatric patients, both as part of treatment and research, in cases of Obsessive-Compulsive Disorder (OCD), and research, in cases of Depression. Current research suggests that there are similarities between Anorexia Nervosa and conditions such as OCD and depression. Given that DBS has shown promise in the treatment of those conditions, this trial was designed to see if it could be an effective therapy for Anorexia Nervosa as well.

This study would be the first exploration of a surgical therapy for refractory AN. The rationale stems from clear and robust evidence pointing at a dysfunctional cortical-subcortical loop driving abnormal behavior, with several important nodes in the loop being particularly important, and recurring, players. The subgenual cingulate plays a role in affective decision making, reward processing, as well as subsequent anxiety and dysphoric mood.

There are currently no brain based, targeted therapies for AN. The scientific significance of this study will be:

i) The first clinical trial exploring deep brain stimulation in an eating disorder population

ii) The first demonstration of the influence of deep brain stimulation on dysfunctional reward processing with co-morbid anxiety/dysphoria

iii) The first 'brain-based' treatment for any eating disorder

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Anorexia Nervosa
Intervention  ICMJE Device: Deep Brain Stimulation
Deep Brain Stimulation (DBS) is a neurosurgical procedure involving the implantation of deep brain electrodes, connected via a subcutaneous extension wire, to an implantable pulse generator (IPG, or 'battery') that is implanted below the collarbone.
Study Arms  ICMJE Experimental: Deep Brain Stimulation
Deep Brain Stimulation
Intervention: Device: Deep Brain Stimulation
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 28, 2019)
15
Original Estimated Enrollment  ICMJE
 (submitted: November 17, 2011)
12
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Female or Male patients between age 20-60
  • Diagnosis of Anorexia Nervosa, restricting or binge-purging subtype as defined by the Diagnostic and Statistical Manual (DSM-IVR)
  • Chronicity and/or Treatment Resistance as demonstrated by some or all of:

    1. A pattern of three year's duration of relentless unresponsiveness to repeated voluntary hospitalizations, characterized by failure to complete treatment of immediate weight relapse following treatment;
    2. pattern of increasing medical instability accompanied by refusal to participate in/lack of responsiveness to intensive expert treatment and increasing medical acuity, lasting at least two years and involving at least two episodes of involuntary feeding;
    3. A pattern of chronic stable AN lasting at least 10 years
  • Able to comply with all testing, follow-ups and study appointments and protocols

Exclusion Criteria:

  • Any past or current evidence of psychosis
  • Active neurologic disease such as epilepsy
  • Alcohol or substance dependence or abuse in the last 6 months, excluding caffeine and nicotine
  • Any contraindication to Magnetic Resonance Imaging (MRI) or Positron Emission Tomography (PET) scanning
  • Likely to relocate or move during the study's one year duration
  • BMI less than 13
  • Presence of cardiac arrhythmias, or other cardiac, respiratory, renal or endocrine conditions as a result of AN or not, that will result in significant risk from a surgical procedure.
  • Pregnancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01476540
Other Study ID Numbers  ICMJE 10-0991-A
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Andres M. Lozano, University Health Network, Toronto
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University Health Network, Toronto
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andres M Lozano, MD, PhD University Health Network, Toronto
Principal Investigator: Blake Woodside, MD Toronto General Hospital
PRS Account University Health Network, Toronto
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP