Deep Brain Stimulation (DBS) of the Nucleus Accumbens for Treatment Resistant Severe and Enduring Anorexia Nervosa: A Phase 1 Open Trial

INTERVENTION: The aims of this study are to determine the efficacy of Deep Brain Stimulation in treatment‐resistant severe and enduring anorexia nervosa. Surgical Procedure: Participants will have the Vercise Gevia Deep Brain Stimulation System surgically implanted by a neurosurgeon according to standard stereotactic procedures. All patients will undergo bilateral implantation. Device implantation is permanent and participants will have the option to continue with the therapy post‐trial or have the device switched or and/or removed. The device provides electrical stimulation to the Nucleus Accumbens (NAcc). Stimulation is provided by controlled delivery of current from a battery in an implantable neurostimulator (INS) connected by extension leads from the body through the neck to electrodes surgically implanted in the brain. Stimulation programs are controlled by the neurologist via the clinical programmer. The total procedure is approximately 3.5 hours in duration. As in the standard procedure patients are woken intra‐operatively and will also complete an image recognition task. Randomisation to ON or OFF stimulation in the blinded phase will occur at this time point in a 50:50 ratio. Randomisation will take place externally and allocation will be concealed from participants and investigators, excepting those responsible for DBS programming. Post‐operatively participants will undergo a CT scan to verify electrode positioning. Stimulation / Programming: Participants will visit the centre for programming of the device by the neuropsychiatrist. Programming sessions will last approximately 30 minutes and are initially weekly, becoming less frequent when parameters are stable. Initial stimulation will commence bilateral stimulation, monopolar configuration. The clinician will initially review the response at weekly‐fortnightly intervals. During initial phase aim is to increase stimulation amplitude by 0.5mA to 1mA per visit unt CONDITION: Anorexia Nervosa; ; Anorexia Nervosa Mental Health ‐ Eating disorders Surgery ‐ Surgical techniques SECONDARY OUTCOME: Body Mass Index (BMI) ; ; The proportion of patients attaining a healthy BMI range of equal to or greater than 18.5. ; ; A measure of relative size based on the height and weight of the individual, calculated as the weight in kilograms divided by the height in metres squared (i.e. kg/m2). Diagnostic and Statistical Manual 5 uses BMI, as a measure of severity of AN. BMI is to be collected preoperatively, whilst baseline BMIs are to be calculated based on patient interviews, weight diaries and medical records. ; ; [Pre‐operatively (2 weeks) ; 1 month post‐surgery ; 4 months post‐surgery ; 7 months post‐surgery ; 10 months post‐surgery ; 13 months post‐surgery ; 16 months post‐surgery ; 18 months post‐surgery] Clinical Impairment Assessment (CIA) ; ; The proportion of patients attaining a CIA global score that is less than 1 standard deviation above community norms < 13.9[Pre‐operatively (2 weeks) ; 1 month post‐surgery ; 4 months post‐surgery ; 7 months post‐surgery ; 10 months post‐surgery ; 13 months post‐surgery ; 16 months post‐surgery ; ; The proportion of patients attaining a 50% reduction in global score, which is considered clinically significant ; [Pre‐operatively (2 weeks) ; 1 month post‐surgery ; 4 months post‐surgery ; 7 months post‐surgery ; 10 months post‐surgery ; 13 months post‐surgery ; 16 months post‐surgery ; 18 months post‐surgery] Eating Disorder Examination Questionnaire (EDE‐Q 6.0) ; ; The proportion of patients attaining an EDE‐Q global score that is less than 1 standard deviation above community norms < 2.74) PRIMARY OUTCOME: The primary outcome is any serious adverse events, or adverse events leading to permanent discontinuation, related to the implantation of or activation of the deep brain stimulation device.; ; Conditions present at screening and do not deteriorate will not be considered adverse events.; ; Hospitalisation due to progression of disease will not be considered a serious adverse event for the purposes of this study.; ; At every study visit patients will be asked how they have been since their last visit in order to elicit any medically related changes in their well‐being. Hospitalisations, new medication or changed concomitant medication regimens. In addition, adverse events will be documented from physical examination findings, clinically significant lab results or other documents related to patient safety. ; ; The following are possible known adverse events: depression, hypermania, mixed bipolar, cardiac air emblous, postopeartive fever, postopeartive infection, headache.; [Adverse events will be recorded from the time the patient signs the informed consent until the final study visit 18 months post‐surgery.] ; 18 months post‐surgery] Cost of healthcare and service utilisation ‐ Medicare service use up to five years post DBS implant[5 years post DBS implantation.] Depression, Anxiety and Stress Scale (DASS) ; [Pre‐operatively (2 weeks) ; 1 month post‐surgery ; 4 months post‐surgery ; 7 months post‐surgery ; 10 months post‐surgery ; 13 months post‐surgery ; 16 months post‐surgery ; 18 months post‐surgery] Montreal Cognitive Assessment (MoCA) ; ; The proportion of patients scoring in the cognitively impaired range post‐intervention (< 26) ; [Pre‐operatively (2 weeks) ; 1 month post‐surgery ; 4 months post‐surgery ; 7 months post‐surgery ; 10 months post‐surgery ; 13 months post‐surgery ; 16 months post‐surgery ; 18 months post‐surgery] Yale‐Brown Obsessive Compulsive Scale (Y‐BOCS) ; ; The proportion of patients attaining a 35% reduction in global score, which is considered clinically significant ; [Pre‐operatively (2 weeks) ; 1 month post‐surgery ; 4 months post‐surgery ; 7 months post‐surgery ; 10 months post‐surgery ; 13 months post‐surgery ; 16 months post‐surgery ; 18 months post‐surgery] INCLUSION CRITERIA: Participants will be selected initially on psychiatric criteria for fulfilling a clear diagnosis of, restricting or binge‐purging subtype, as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) Be of a severe, enduring and treatment‐resistant AN: * BMI between 13 to 17.5 * Duration of severe AN of at least 7 years * Treatment resistance: lack of response to at least two treatments such as evidence‐based psychotherapy, day treatment and inpatient weight regain • Significant functional impairment • Age 18‐65 years • Able to freely provide verbal and written informed consent • Able to comply with all assessment, protocols and follow‐ups • Approved for treatment by the Mental Health Review Tribunal (MHRT)