Phase I Trial of MR-guided Focused Ultrasound (MRgFUS) Bilateral Capsulotomy for the Treatment of Refractory Major Depression

Sunnybrook Health Sciences Centre1 site in 1 country18 target enrollmentJanuary 19, 2018

ConditionsMajor Depressive Disorder

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: Major Depressive Disorder
Sponsor: Sunnybrook Health Sciences Centre
Enrollment: 18
Locations: 1
Primary Endpoint: Incidence of Treatment-Emergent Adverse Events
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

The proposed study is to evaluate the safety and initial efficacy of MRgFUS for patients with treatment-refractory Major Depression. This study is designed as a prospective, single arm, nonrandomized study. Assessments will be made before and after MRgFUS for adverse events related to treatment, for clinical symptom relief, and quality of life (QoL). The target in the brain chosen for ablation will be the anterior limb of the internal capsule (i.e 'capsulotomy').

Registry

clinicaltrials.gov

Start Date

January 19, 2018

End Date

July 28, 2021

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Sunnybrook Health Sciences Centre

Responsible Party

Principal Investigator

Dr. Nir Lipsman

Princiapl Investigator

Sunnybrook Health Sciences Centre

Eligibility Criteria

Inclusion Criteria

•Men and women ≥20 and ≤80 years of age.
•Patients who are able and willing to give consent and physically and practically able to attend study visits, as determined by both study Psychiatrist and the surgeon.
•DSM-V diagnosis of major depressive episode, as a component of an Axis I disorder, such as Major Depressive Disorder, Bipolar Disorder, Anxiety Disorder, Eating Disorder, Substance Abuse/Dependence Disorder ,or Personality Disorder
•At least 5-year illness history of the primary disorder and at least 6 months since the onset of the first episode of major depression.
•A minimum score of 20 on the Hamilton Depression Rating Scale (HAMD) when depressed (patients with bipolar disorder may be rapid cycling, but have to have at least 2 weeks of major depression at the time the HAMD is conducted)
•Medication-refractoriness as determined by an adequate dose and duration of standard psychiatric treatments (including psychotherapy and/or pharmacology) as determined by two psychiatrists associated with the study. Including specifically:
•Failed to respond or tolerate adequate trial of three or more medications accepted as first line in the treatment of depression
•Failed to respond or tolerate augmentation with or combination,of at least 2 medications known to be first line treatments for depression
•An adequate trial of cognitive behavioural therapy or other evidence-supported psychotherapy, delivered by a therapist experienced in treating depression
•Able to communicate sensations during the ExAblate MRgFUS treatment

Exclusion Criteria

•Patients with unstable cardiac status \[e.g. Unstable angina pectoris on medication, Patients with documented myocardial infarction within six months, Congestive heart failure requiring medication (other than diuretic), Patients on anti-arrhythmic drugs, Severe hypertension (diastolic BP \> 100 on medication)\]
•Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
•Severely impaired renal function (estimated glomerular filtration rate \< 30ml/min/1.73 m2) or receiving dialysis
•Laboratory biochemical evidence of abnormal bleeding and/or coagulopathy, including risk factors for intraoperative or postoperative bleeding (platelet count less than 100,000 per cubic millimeter or abnormal INR)
•Cerebrovascular disease (e.g. CVA within 6 months) or history of intracranial hemorrhage
•Untreated, uncontrolled sleep apnea
•Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure
•Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment
•Are participating or have participated in another clinical trial in the last 30 days
•Patients unable to communicate with the investigator and staff.

Outcomes

Primary Outcomes

Incidence of Treatment-Emergent Adverse Events

Time Frame: 1 year

Safety of the ExAblate transcranial treatment will be determined by an evaluation of the incidence and severity of procedure related complications from the treatment day visit through the 12-month post-treatment time point. All events that are not procedure related will also be captured and recorded.

Secondary Outcomes

Clinical efficacy will be measured using the Hamilton Rating Scale for Depression (HAMD)(1 year)
Clinical efficacy will be measured using the Beck Depression Inventory (BDI)(1 year)
Quality of Life will be measured using the Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ)(1 year)
Clinical efficacy will be measured using the Montgomery Asberg Depression Rating Scale (MADRS)(1 year)
Clinical efficacy will be measured using the Columbia-Suicide Severity Rating Scale (C-SSRS)(1 year)