Novel Pharmacology

Ongoing Studies

Overview:
Nitrous oxide (N2O), also known as laughing gas, is an anesthetic gas that is frequently encountered in dental offices. However, it is also used in a variety of settings including labour and delivery units, as well as operating rooms. It is inexpensive and is on the World Health Organization’s list of essential drugs. Nitrous oxide is believed to work as an NMDA receptor antagonist, a mechanism shared with ketamine. However, unlike ketamine, it has minimal side effects. Current evidence has demonstrated that a single administration of nitrous oxide has been shown to decrease depressive symptoms, and there is ongoing research examining the effects of nitrous oxide in depression. Thus, we intend to carry out a research study to explore the clinical efficacy and functional outcomes of repeated nitrous oxide administrations.

Eligibility:

    • Diagnosis of Major Depressive Disorder
    • Have not seen results following a previous course of treatment for the Major Depressive Disorder such as pharmaceuticals, psychotherapy, or rTMS
    • Male or Female, aged 18-65 years old

Treatment Protocol:

    • This is a pilot study that will utilize repeated administrations of nitrous oxide gas using a randomized approach.
    • Participants will be randomized to receive either inhaled nitrous oxide gas plus infused saline solution, or placebo (inhaled oxygen gas with infused midazolam–a different sedative agent)
    • Participants will be given 50% mg/mL of nitrous oxide to inhale plus a saline solution delivered intravenously, or 50% oxygen gas to inhale plus 1 mg/mL of midazolam delivered intravenously. Both interventions will last one hour, and will be administered once a week for four weeks.
    • Participants will be followed for 90 days after completion of treatment.

Neurostimulation is an evolving therapy for treatment-resistant depression that involves the application of electromagnetic stimuli (magnetic field or electric current) to the brain. Applied magnetic or electrical stimulus stimulates nerve cell activity and employs the body’s natural biological response by releasing neurotransmitters – specialized chemicals that allow brain cells to communicate with each other. Brain stimulation modulates the firing pattern of nerve cells and stabilizes the interaction between different parts of the brain. The treatment is non-invasive, meaning that no surgery is required.

 

The Interventional Psychiatry Program at St. Michael’s Hospital carries out a number of research studies to explore the clinical efficacy and functional outcomes of the following brain stimulation treatments:

 

1) Temporal Interference Stimulation (TI)

2) Repetitive Transcranial Magnetic Stimulation (rTMS)

3) Functional Electrical Stimulation (FES)

4) Transcranial Ultrasound Stimulation (TUS)

 

The ultimate goal of this research is to develop novel clinical tools for the diagnosis, prognosis, and treatment of resistant depression. The studies explore how certain biological markers in the form of behavioural measures, EEG, or MRI can be used to clinically quantify and predict treatment response to brain stimulation. This research focuses on personalized medicine approaches and aims to determine optimal individual treatment parameters in each patient for the most beneficial outcome.

 

Below is a list of our current clinical trials, and the contact information for the study coordinator, who can answer any questions you may have about the study, including the referral and intake process. Research funds are available to cover the full cost of treatment for participants who wish to enroll in these trials.

 

Study One: Temporal Interference (TI) for Depression

Overview:

Temporal Interference (TI) stimulation is a novel promising form of non-invasive transcranial electrical stimulation that is the first of its kind to modulate brain regions located deep below the surface. Non-invasive Brain stimulation techniques have been around for a while but their functional application has been limited to the outer parts of the brain. Depression, however, is known to be also associated with a brain area called the subgenual cingulate cortex located deep below the surface. The potential ability of TI to target this region gives it an unlimited potential in advancing scientific knowledge of brain function and offers a promising therapeutic application for major depression.

 

Eligibility:

 

  • Diagnosis of Major Depressive Disorder
  • Have not seen results following a previous course of treatment for the Major Depressive Disorder such as pharmaceuticals, psychotherapy, or rTMS
  • Male or Female, aged 18-65 years old

 

Treatment Protocol:

  • This is a pilot study that will utilize repeated administrations of brain TI using a randomized approach
  • Participants will be randomized to receive either a 30 minute TI, or a 30 minute placebo stimulation
  • 2 weeks of daily TI sessions administered during weekdays only, for a total of 10 TI sessions
  • An MRI will be taken both prior to and following the course of treatment
  • Weekly assessments throughout treatment
  • Participants will be followed for 30 days after completion of treatment
  • An MRI will be taken both prior to and following the course of treatment
  • Weekly assessments throughout treatment
  • Participants will be followed for 30 days after completion of treatment.

Digital Interventions & Intelligence Group (DiiG)

DiiG is a collaborative initiative led by Dr. Venkat Bhat (Psychiatry-UHT-St. Michael’s) and Dr. Sri Krishnan (Biomedical Engineering-Toronto Metropolitan University)

Digital intervention projects revolve around digital interventions and intelligence. DiiG deploys various digital modalities including:  Virtual Reality (VR), wearable devices, and web-based interventions. Our multidisciplinary team is at the intersection of engineering, advanced data analytics and psychiatry, and uses digital platforms, such as wearable devices and mobile phones, to learn and assess a person’s mental health and well-being. Through this, we aim to create personalized interventions to manage and prevent potential harm.

One example of our digital platforms is the use of the Greenspace Mental Health platform, a commercial website that allows for the monitoring and measuring clinical data. If you wish to have an idea of the platform you can access their website here: www.greenspacehealth.com

This platform is fully compliant with patient/participant confidentiality standards such as the US HIPPA and corresponding Canadian PHIPA/PIPEDA privacy laws.  Images of the Greenspace platform and its functionalities can be seen in the Web- Based Platform section.

 

Functionalities of the digital app can be seen below:

Download Page

DiiG LAMP (Learn, Assess, Manage, Prevent)

 

 

 

 

 

 

 

 

 

DiiG Functionality

Study 1: Digital Interventions to Understand and Mitigate Moral Distress in the COVID-19 Context

Study Coordinator: Walter Sim (Walter.Sim@unityhealth.to)

Overview:

The purpose of this study is to use a Virtual Reality (VR) set up, a web-based platform, and a wearable device to understand and reduce the moral distress phenomenon faced by nursing professionals during the COVID-19 pandemic. Stress, anxiety, distress, and depression are exceptionally high among healthcare workers at the frontline of the COVID-19 pandemic. Healthcare workers have reported acting in ways that are contrary to their moral values, integrity, and professional commitments as a result of witnessing or participating in decisions or actions that degrade their integrity, creating moral distress and injury. Understanding of factors underlying distress and resilience in complex moral contexts are limited, and there are no evidence-based interventions for the moral distress that frontline healthcare workers face during pandemic contexts.

 

The use of all three components (the VR, web-based platform, and a wearable device) will be essential for a thorough understanding of the moral distress phenomenon. The Virtual Reality (VR) aspect of the study will simulate the decision-making of nurses in morally challenging situations and complex environments to assess and reduce moral distress. Simultaneously, the web-based platform and the wearable device will be used to help understand moral distress in nursing professionals.

 

We will use this data to pursue novel research in signal processing and classification for short- and long-term moral distress effects. We will use the physiological signals and the VR scenarios to identify features that correlate to moral distress and we will use active data collected from our web-based application to determine fluctuations in individuals’ mood and well-being.

Eligibility:

  • Nursing professionals from different institutions in Ontario.
  • Ownership of a smartphone.

The current study has no exclusion criteria.

Intervention Protocol:

  • Once participants agree to participate in the study, they will select a time to attend the VR component of the study and will receive login access to Greenspace and Oura ring platforms.
  • The platforms allow for collection of various forms of active data (data collected while the participant is using the app, e.g. surveys assessing anxiety or mood), and passive data (sleep, activity and other physiological data collected from Oura Ring).
  • For the VR simulation, participants will wear a head-mounted display (HMD) and handheld motion-tracked controllers. During the simulation, participants will be placed in a hospital scenario. This simulation will examine the thoughts, feelings, and behaviours behind difficult decision-making in a virtual environment. The decisions participants make in the simulation may be related to a morally challenging situation.
  • The anticipated duration for the study is 6 months.

The Oura Ring wearable and its respective mobile app:

Source: https://ouraring.com/

Virtual Reality Set

Source: https://uploadvr.com/oculus-quest-2-128-model-on-sale/

Study 2: Digital Registry within the Interventional Psychiatry Program

Study Coordinator: Walter Sim (Walter.Sim@unityhealth.to)

Overview:

​Digital devices have the unique potential to capture data related to a patient’s behaviour, self-reported symptoms, and physiological function in real time. Collected digital data such as step count, sleep timing, and surveys may help clinicians and patients monitor mental health status and symptoms outside of medical offices.

The goal of this study is to determine whether it is practical to use digital technology to collect data about a patient’s health and how they are feeling over a period of time. We will be doing this by having patients use a web platform (Greenspace) and REDCap (Research Electronic Data Capture), a web-based software to collect demographic and survey information. Both Greenspace and REDCap online software will ask questions about mental health at certain time points. Additionally, participants will have the option to wear a device (Oura Ring) that provides us with more detailed health data (e.g., sleep patterns and heart rate). Once all the data is collected, we will store it in a registry and see if we can use it to help improve our care here in the program.

In the Interventional Psychiatry Program, a registry of digital data will be created over time to help us: (1) understand the effectiveness of the program; (2) to predict if a patient will benefit from this program; (3) monitor and identify early signs of depressive relapse (symptom worsening) in patients.

Eligibility:

  • Referred to the Interventional Psychiatry Program (IPP) at Unity Health Toronto
  • 18 years of age or older
  • Ownership of a smartphone.

Exclusion criteria:

  • Participants involved in experimental interventions such as take-home neurostimulation, nitrous oxide, Stellate Ganglion Block.

Intervention Protocol:

  • This Program will be creating a registry, where data will be digitally collected while patients are enrolled in the Interventional Psychiatry Program.
  • There will be a web platform in which participants will be required to log-in and answer surveys that monitor stress-related symptoms every Monday, Wednesday, Friday, and Weekends. Additionally, participants will use an additional web-based tool for demographic, clinical, and mental health data gathering called REDCap. The mental health data to be collected will involve three scales that will measure depression, anxiety, and suicidality symptoms.
  • Participants might be offered to use a wearable device called Oura ring, which will monitor body temperature, heart rate, respiratory rate, and physical activity.
  • The platforms allow for collection of various forms of active data (data collected while the participant is using the app, e.g. surveys assessing anxiety or mood), and passive data (data collected whether or not the user is actively using the app, e.g. heart rate, sleep data, and activity data).

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