Deep Brain Stimulation for the Treatment of Refractory Anorexia Nervosa

NCT ID: NCT01476540

Last Updated: 2019-10-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2014-02-28

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

Conditions

Anorexia Nervosa

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Deep Brain Stimulation

Deep Brain Stimulation

Group Type: EXPERIMENTAL

Deep Brain Stimulation

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: DEVICE

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Andres M. Lozano

Neurosurgeon, Professor of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andres M Lozano, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Blake Woodside, MD

Role: PRINCIPAL_INVESTIGATOR

Toronto General Hospital

Locations

Toronto Western Hospital

Toronto, Ontario, Canada

Countries

Canada

References

Lipsman N, Lam E, Volpini M, Sutandar K, Twose R, Giacobbe P, Sodums DJ, Smith GS, Woodside DB, Lozano AM. Deep brain stimulation of the subcallosal cingulate for treatment-refractory anorexia nervosa: 1 year follow-up of an open-label trial. Lancet Psychiatry. 2017 Apr;4(4):285-294. doi: 10.1016/S2215-0366(17)30076-7. Epub 2017 Feb 24.

Reference Type: DERIVED

PMID: 28238701 (View on PubMed)

Lipsman N, Woodside DB, Giacobbe P, Hamani C, Carter JC, Norwood SJ, Sutandar K, Staab R, Elias G, Lyman CH, Smith GS, Lozano AM. Subcallosal cingulate deep brain stimulation for treatment-refractory anorexia nervosa: a phase 1 pilot trial. Lancet. 2013 Apr 20;381(9875):1361-1370. doi: 10.1016/S0140-6736(12)62188-6. Epub 2013 Mar 7.

Reference Type: DERIVED

PMID: 23473846 (View on PubMed)

Other Identifiers

10-0991-A

Identifier Type: -

Identifier Source: org_study_id