Ketamine + Virtual Reality for Depression

(TREASURE Trial)

Overseen By Fahad Alam, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sunnybrook Health Sciences Centre

Must be taking: IV ketamine

Must not be taking: Non-prescribed substances

Disqualifiers: Psychosis, Substance misuse, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating depression by combining ketamine, a fast-acting medication, with virtual reality (VR) to determine if it is more effective than ketamine alone. Researchers aim to enhance ketamine's effects through VR by creating an immersive experience. They seek to discover if this combination can aid individuals with depression unresponsive to other treatments. Participants should have treatment-resistant depression and already be receiving ketamine therapy. The goal is to assess if this approach merits further study in a larger trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for depression.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must not have used non-prescribed substances or alcohol within 48 hours before treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ketamine can quickly reduce depression symptoms in many people. In a large study with over 9,000 patients, more than half experienced a significant improvement, with their symptoms decreasing by 50% or more. This is promising because traditional antidepressants often take weeks to work, while ketamine acts much faster.

Regarding safety, ketamine is generally well-tolerated. However, some people might feel disconnected from reality, experiencing vivid dreams or hallucinations. These effects are usually temporary.

Using virtual reality (VR) with ketamine is a newer method. Early findings suggest that combining VR with ketamine might improve treatment results for depression. While VR is generally safe, its combination with ketamine remains under study.

This trial is in Phase 3, indicating that earlier studies have shown enough safety evidence to test it on larger groups. Those considering joining a trial should consult healthcare providers to understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine ketamine, a fast-acting antidepressant, with innovative virtual reality (VR) technology to potentially enhance its effects. Unlike traditional antidepressants like SSRIs, which can take weeks to work, ketamine can improve symptoms in just hours, targeting glutamate pathways in the brain. The addition of VR aims to create a calming, immersive experience during treatment, which could further boost mood and reduce anxiety. This combination offers a unique approach that could provide quicker and more effective relief for depression compared to current standard treatments.

What evidence suggests that this trial's treatments could be effective for depression?

Research shows that ketamine can quickly reduce symptoms of depression, especially for those unresponsive to other treatments. This rapid effect distinguishes it from other antidepressants, which may take weeks to work. In this trial, some participants will receive ketamine alone, while others will receive ketamine combined with virtual reality (VR) using an Oculus VR headset. Early studies suggest that VR with ketamine might enhance its effectiveness. VR can create engaging experiences that may help the brain respond more to the treatment. Therefore, combining ketamine with VR could be a stronger option for treating depression than using ketamine alone. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults with treatment-resistant depression, meaning their condition hasn't improved after trying other medications. Participants must be willing to undergo ketamine treatments and use a VR headset if assigned to that group.

Inclusion Criteria

I am mentally alert and can engage with and respond to immersive content.

I am prescribed IV ketamine by my doctor and need at least 4 treatments per course.

My psychiatrist has approved me for outpatient ketamine treatment.

Exclusion Criteria

Using non-prescribed substance (e.g., cannabis) or alcohol use within the preceding 48 hours of treatment

Previous ketamine use

Inability to communicate with the study team

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I - VR Software Development

Participants provide feedback to develop the VR software for the study population

Not specified

Phase II - Treatment

Participants receive 4 ketamine treatments over 2 weeks, with half using VR concurrently

2 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

1, 2, 3-week and 1 and 3 month follow-ups

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine
• Oculus VR headset

Trial Overview

The study is testing whether combining ketamine treatments with immersive virtual reality (using an Oculus VR headset) can more effectively treat symptoms of depression compared to ketamine alone. It's a pilot trial aimed at setting the stage for larger studies.

How Is the Trial Designed?

Group I: VR-Ketamine (VR-K) Experimental Treatment 2 Interventions

Participants will receive a standard course of ketamine treatment. At the onset of each ketamine therapy session, participants will be provided with an Oculus VR headset, and will be immersed in a tailor-made virtual environment of positive outdoor scenes.

Group II: Ketamine alone Active Control 1 Intervention

Participants will receive a standard course of ketamine treatment.

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Published Research Related to This Trial

Oral ketamine has shown effectiveness in treating severe depression, including treatment-resistant cases and those with suicidal ideation, based on various studies including randomized controlled trials with doses ranging from 0.25 to 7 mg/kg.

Despite its lower bioavailability (20%-25% reaching the bloodstream), oral ketamine is well tolerated and can be adjusted for individual needs, making it a practical option for depression treatment alongside conventional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. Andrade, C.[2019]

In a systematic review of 93 studies involving 3756 participants receiving sub-anesthetic doses of ketamine for psychiatric disorders, only four serious adverse medical events (MSAEs) were reported, resulting in an incidence of approximately 0.1%, indicating a very low risk of serious complications.

No serious cardiac events or deaths were observed, and most studies effectively screened out high-risk patients, suggesting that with proper medical screening, ketamine can be administered safely for psychiatric treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the incidence of medical serious adverse events in sub-anesthetic ketamine treatment of psychiatric disorders. Hovda, N., Gerrish, W., Frizzell, W., et al.[2023]

In a study of 9016 patients receiving ketamine intravenous therapy (KIT) for depression, 53.6% showed a significant response (≥50% reduction in depression scores) within 14-31 days, indicating KIT's efficacy in real-world settings.

While most patients benefited from KIT, a small percentage (8.4%) experienced worsening depressive symptoms, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings. McInnes, LA., Qian, JJ., Gargeya, RS., et al.[2023]

In a study involving 56 participants, including 26 patients with treatment-resistant depression (TRD), ketamine infusions were found to significantly enhance belief updating after receiving good news compared to bad news, indicating a cognitive effect that may contribute to its rapid antidepressant response.

The study revealed that ketamine treatment led to asymmetrical learning rates, where patients updated their beliefs more positively after good news, which was linked to early improvements in depression symptoms, suggesting potential for integrating ketamine with psychotherapy for mood disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression. Bottemanne, H., Morlaas, O., Claret, A., et al.[2022]

This systematic review analyzed 60 studies on the safety of ketamine for treating depression, revealing that acute doses of ketamine led to more frequent side effects, including psychiatric and cardiovascular issues, compared to placebo.

There is a notable lack of data on the long-term safety and effects of repeated ketamine dosing, highlighting the need for large-scale clinical trials to better understand its safety profile over extended use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side-effects associated with ketamine use in depression: a systematic review. Short, B., Fong, J., Galvez, V., et al.[2019]

Ketamine and esketamine demonstrate rapid antidepressant effects, with improvements in clinical response observed within 40 minutes to 1 week for ketamine and 2 hours to 4 weeks for esketamine, along with reductions in depression scores and suicidality.

Despite their effectiveness, the long-term safety and efficacy of ketamine and esketamine remain uncertain, and the overall quality of the studies reviewed was critically low, highlighting the need for more rigorous research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses. Lima, TM., Visacri, MB., Aguiar, PM.[2022]

Subanaesthetic doses of ketamine have shown substantial efficacy in treating depression, with response rates averaging 77% and remission rates around 43% within 4 to 72 hours after a single dose.

Despite the rapid improvement in mood for many patients, the effects are often short-lived, highlighting the need for further research on dosing regimens and strategies to maintain the antidepressant response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine as a new treatment for depression: a review of its efficacy and adverse effects. Katalinic, N., Lai, R., Somogyi, A., et al.[2013]

Subcutaneous (SC) administration of racemic ketamine and esketamine has shown rapid and robust antidepressant effects in both unipolar and bipolar patients, with response and remission rates ranging from 50% to 100% after single or multiple doses.

The studies indicated that SC ketamine is generally well-tolerated, with only transitory side effects, making it a promising and cost-effective treatment option for depression, especially in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. Cavenaghi, VB., da Costa, LP., Lacerda, ALT., et al.[2021]

There is currently no standardized safety monitoring protocol for off-label use of generic ketamine, and safety monitoring for intranasal esketamine varies by jurisdiction, leading to potential gaps in patient safety.

The Ketamine Side Effect Tool (KSET) is recommended as a comprehensive tool for monitoring both acute and long-term side effects of ketamine and esketamine treatments, addressing the lack of agreed frameworks for safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. Bayes, A., Short, B., Zarate, CA., et al.[2023]

In a study of 201 adults with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD), intravenous (IV) ketamine significantly reduced symptoms of anxiety, irritability, and agitation in those with mixed features, indicating its effectiveness in treating these symptoms.

Participants with anxiety, irritability, and agitation (AIA) experienced greater reductions in overall depressive symptoms and suicidal ideation compared to those without AIA, suggesting that IV ketamine could be a rapid treatment option for adults with mood disorders presenting with mixed features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder. McIntyre, RS., Lipsitz, O., Rodrigues, NB., et al.[2021]

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Ketamine + Virtual Reality for Depression (TREASURE Trial)

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Patients must have completed the acute series of treatment and weekly optimization phases of ketamine/esketamine treatment, and currently receiving continuation ...