Psychiatry trials

Sunnybrook Health Sciences Centre in Toronto, Canada, is a recognized world-leader in MRgFUS technology, having pioneered the procedure in a broad range of neurologic and psychiatric conditions. The success of MRgFUS in disorders of motor circuitry, such as tremor, has led to its application in other ‘circuit’ conditions of the brain, such as mood and anxiety disorders, leveraging decades long experience in ablative surgery for these highly challenging diseases.

MRgFUS capsulotomy for neuropsychiatric disorders has been investigated at Sunnybrook and other centres globally and found in several published reports to be safe and associated with significant long-term response rates.

The management of mood and anxiety disorders is challenging and multi-faceted, and despite guideline concordant care, up to 1/3 of patients remain symptomatic despite optimal treatment. For these patients, direct to brain interventions have been developed and include a range of options from less invasive such as repetitive transcranial magnetic stimulation (rTMS), and electroconvulsive therapy (ECT) to surgical strategies such as deep brain stimulation (DBS) and MRgFUS. Given it’s less invasive and targeted nature, MRgFUS has emerged as an important treatment option, with implications for patients well-being, clinical outcomes and quality of life.

There remains valuable information to be learned from patients’ responses to treatment with MRgFUS, as investigators further develop this surgical tool. Outcomes are variables monitored in a study, to verify the effect of an intervention on the participant’s health. A primary outcome is the variable most relevant and important to address the research question. For example, a primary outcome measured in MRgFUS studies for depression focused on depression severity, whereas a primary outcome measured in an obsessive compulsive disorder trial focuses on symptoms of anxiety. However, the effects of neuromodulation may not be limited to changes in these symptoms, as patients also report changes in quality of life and everyday functioning, and there may also be critical changes occurring in the brain that predict a treatment’s effect, be it positive or negative (e. imaging biomarkers). These factors are critical to consider when evaluating whether treatments are successful and will help inform both our understanding of the disease, and our ability to develop future treatments.

The goal of this study is to better understand and characterize the clinical and imaging outcomes of patients undergoing treatment with MRgFUS for OCD and depression. We will assess clinical outcomes, imaging parameters, cognitive and neuropsychologic performance, and quality of life, before and at several time points after treatment. The results will allow us to better prepare patients for what to expect following treatment with MRgFUS, and to better understand how the brain responds to direct to circuit interventions.

This study will take place at Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada. All patients with refractory OCD and Depression who are considered eligible for treatment with MRgFUS are eligible for this study. Patients who are assessed for MRgFUS but who do not undergo treatment (either because they do not meet eligibility criteria or because they opt out) are also eligible for this study. These patients will serve as a control group and will allow us to better understand changes specific to the treatment with neuromodulation.

Patients undergoing MRgFUS will be assessed before and after treatment. The follow-up visits occur at 1, 3, 6, 12, 18 and 24 months after MRgFUS (some of these may be done virtually). Patients who do not undergo MRgFUS may be invited back for one or two follow-up visits.

PI: Dr. Nir Lipsman, Neurosurgeon, Sunnybrook Health Sciences Centre (nir.lipsman@sunnybrook.ca)

Contact: Anusha Baskaran (416-480-6100 ext. 61650); anusha.baskaran@sunnybrook.ca

A large proportion of patients with Obsessive Compulsive Disorder (OCD) continue to have symptoms despite various medical and psychiatric treatments.

MR-guided Focused Ultrasound thermal ablation offers the possibility of reaching and treating an area deep in the brain, called the anterior limb of the internal capsule (ALIC) by creating lesions to precisely targeted regions. This does not require open surgical approaches and lesions are generated in real-time under MR image guidance.

The proposed study is to evaluate the safety and efficacy of focused ultrasound for patients with treatment-resistant OCD. Assessments for any adverse events, clinical symptom relief, and quality of life will be made before and after the focused ultrasound treatment.

Ten patients, aged 20-80, will undergo one round of focused ultrasound, and then be assessed for severity of depression and level of functioning up to 12 months following treatment.

For more information or to inquire about eligibility for the trial, please email harquailcentre@sunnybrook.ca. Please indicate in the subject line your diagnosis and which study you are inquiring about.

In this North American first study, researchers are investigating the safety and effectiveness of focused ultrasound to help patients with treatment-resistant Major Depression.. About 10% of people with recurrent major depression, will have treatment resistant Major Depression making them at risk for continued morbidity, and in some cases mortality. In Ontario this represents around 190,000 people.

This study is evaluating the safety and efficacy of MRgFUS for patients with treatment-resistant Major Depression and will target and lesion the anterior limb of the internal capsule (ALIC).Assessments for any adverse events, clinical symptom relief, and quality of life will be made before and after the focused ultrasound treatment.

In this trial, six patients, aged 25-80 years, will undergo one round of focused ultrasound, and then be assessed for severity of depression and level of functioning up to 12 months following their treatment.

For more information or to inquire about eligibility for the trial, please email harquailcentre@sunnybrook.ca. Please indicate in the subject line your diagnosis and which study you are inquiring about.

The purpose of this study is to determine the safety and feasibility of DBS in people with Post-traumatic Stress Disorder (PTSD). Research shows there are similarities between the symptoms of PTSD and those of anxiety and depression and DBS has shown promise in the treatment of those conditions.

In this trial five patients, aged 18-70 years will undergo a DBS implant. The length of this study from the time of enrollment, is approximately 14 months.

For more information or to inquire about eligibility for the trial, please email harquailcentre@sunnybrook.ca. Please indicate in the subject line your diagnosis and which study you are inquiring about.

Treatment refractory alcohol use disorder (AUD) is a chronic and debilitating disease associated with high morbidity. Despite advances in neuroimaging, genetics, pharmacology and psychosocial interventions,, little progress has been made in altering the natural history of the condition or its outcome.

This study will investigate surgical therapy for the treatment of refractory alcoholism. It will focus on a part of the brain known as the core of the nucleus accumbens, which plays a role in addiction. It is also an area known to be successful in managing alcohol cravings and in helping maintain abstinence.

Five subjects will be enrolled in this open label trial for the one year.. The primary objective of the trial is to investigate the safety and efficacy of DBS in patients with treatment refractory AUD. This will be determined by various outcome measures that will include validated scales to assess addiction and craving behaviours.

Magnetic resonance-guided focused ultrasound (MRgFUS) can be used to perform ablative neurosurgical procedures, mitigating the risks of open cranial approaches. To date, MRgFUS approved, for the treatment of patients with refractory essential tremor, and there is a growing experience in refractory psychiatric illnesses. The ability to generate a lesion, depends primarily on the patient’s skull density. In this study, we use a new technique called Echo-focusing to enhance efficiency of ultrasound transmission through the skull and be able to treat those who would otherwise be ineligible for a lesioning procedure.

The objective of the proposed study is to evaluate the safety and effectiveness of Echo-Focusing using Exablate Neuro as a tool for treating patients with treatment-refractory neurologic and psychiatric disorders: refractory essential tremor, major depressive disorder (MDD), obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD) (with comorbid MDD or OCD), and anorexia nervosa (with comorbid MDD or OCD). We believe that this will be safer than and as effective as open neurosurgery, while mitigating the risks of open cranial approaches.

A total of 46 subjects will be enrolled. Safety 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.

For more information or to inquire about eligibility for the trial, please email harquailcentre@sunnybrook.ca. Please indicate in the subject line your diagnosis and which study you are inquiring about.