Major Depressive DisorderNCT06178731
Virtual Reality Reward Training and Transcranial Magnetic Stimulation for Depression
A study testing rTMS and Virtual Reality in people with Major Depressive Disorder, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial summary
Anhedonia is a core feature of major depressive disorder (MDD) (DSM-5). Functional magnetic resonance imaging (fMRI) studies have associated anhedonia in MDD with altered frontostriatal activity and functional connectivity relative to controls. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- rTMS and Virtual Reality
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteCanada
- Study dates
- 29 Oct 2021to 29 Oct 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Female or male patients between ages 18-65 2. Diagnosis of major depressive disorder as defined by the Diagnostic and Statistical Manual fifth edition (DSM-5) 3. Hamilton Rating Scale for Depression (17-item) score of at least 16 4. Clinically significant anhedonia as defined by a Smith-Hamilton Pleasure Scale (SHAPS) score of at least 20 (Krystal et al., 2020) 5. On a stable antidepressant regimen for at least 4 weeks before treatment which can continue during treatment and agreement to not make changes or additions to psychotropic medications during the course of their participation in the study 6. Ability to provide informed consent and comply with all testing, follow-ups and study appointments and protocols
Who cannot join
- Any past or current evidence of psychosis or mania
- Active neurologic disease
- Any lifetime history of seizures
- Alcohol or substance dependence or abuse in the last 6 months, excluding caffeine and nicotine
- Current active suicidal ideation
- Personality disorder deemed to be the primary pathology
Show all 13Show fewer
- Taking more than 2 mg lorazepam (or an equivalent) or any anticonvulsant
- Previous rTMS treatment
- Lifetime history of non-response to an adequate course (minimum 8 treatments) of electroconvulsive therapy
- Previous or current engagement in ketamine treatment for major depressive disorder
- Any contraindication to MRI scanning
- Likely to relocate or move out of the country during the study's duration (3-4 months from baseline visit)
- Frequent motion sickness
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Anusha Baskaran, PhD, 416-480-6100 ext. 61650, anusha.baskaran@sunnybrook.ca
About this study
Anhedonia is a core feature of major depressive disorder (MDD) (DSM-5). Functional magnetic resonance imaging (fMRI) studies have associated anhedonia in MDD with altered frontostriatal activity and functional connectivity relative to controls. Conversely, antidepressant treatment is associated with increased ability for patients with MDD to sustain frontostriatal activity in a manner predictive of decrease in anhedonia and gains in daily positive affect. Novel interventions are needed to address anhedonia. Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) has been shown to activate striatal reward circuits. Positive Affect Treatment (PAT) was developed to treat deficits in reward processing; a critical skill patients are trained on in PAT involves recounting and savouring of positive experiences. However, amotivation impedes some patients from engaging in positive activities, prompting the development of virtual reality reward training (VR RT) for this skill. Evidence is building that brain state at the time of rTMS impacts its therapeutic effect. For example, imaginal exposure and individualized symptom provocation just prior to rTMS enhances its therapeutic effect on post-traumatic stress disorder and obsessive-compulsive disorder, respectively. It is unknown whether VR RT can augment rTMS for MDD and if so whether it is mediated by enhancing changes in frontostriatal activity or functional connectivity.
The current study is significant for multiple reasons. As mentioned, there is a paucity of effective treatments for anhedonia and this study may inform development of a novel treatment strategy that harnesses findings from affective neuroscience. Recent economic analysis suggests that rTMS can be more cost-effective than pharmacotherapy or ECT for treatment-resistant depression (Ontario Health, 2021). Our findings will provide insight on ways to synergize specific psychotherapeutic techniques with targeted stimulation of brain circuits to more effectively treat subtypes of depression.
Read the detailed description
This is a non-blinded, randomized sham-controlled trial for effectiveness and feasibility of virtual reward reality training and rTMS for MDD with two arms. Patients with MDD who meet inclusion and exclusion criteria will be identified and recruited from the practices of Sunnybrook psychiatrists. Subjects will undergo either: i) VR RT + rTMS (n = 17) or ii) VR sham + rTMS (n = 17). Each treatment session involves: 12-15 min VR viewing, 15 min descriptive and imaginal recounting followed immediately by 3 min rTMS delivery with iTBS to the left DLPFC. The study will proceed according to the schedule laid out below. Both patients and treating team will be aware of all treatment parameters at all times.
- Conditions
- Major Depressive Disorder
- Being tested
- rTMS, Virtual Reality
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMSDevice
3 min rTMS delivery with iTBS to the left DLPFC
Virtual RealityOther
2-15 min VR viewing, 15 min descriptive and imaginal recounting
| Study group | Role | What they receive |
|---|---|---|
| Virtual reality + rTMS | Experimental | Each treatment session involves: 12-15 min VR viewing, 15 min descriptive and imaginal recounting followed immediately by 3 min rTMS delivery with iTBS to the left DLPFC. Receives: Device: rTMS; Other: Virtual Reality |
| Virtual reality sham + rTMS | Sham comparator | Each treatment session involves: 12-15 min VR viewing, 15 min descriptive and imaginal recounting followed immediately by 3 min rTMS delivery with iTBS to the left DLPFC. Receives: Device: rTMS; Other: Virtual Reality |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Hamilton Depression Rating Scale
Mood symptoms, higher scores mean worse outcome. Min = 0, Max = 52
Measured: up to 4 weeks after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2023
- Study start29 Oct 2021
- Primary completion29 Oct 2024 (estimated)
- Study completion29 Oct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- This is a non-blinded, randomized sham-controlled trial for effectiveness and feasibility of virtual reward reality training and rTMS for MDD with two arms. Patients with MDD who meet inclusion and exclusion criteria will be identified and recruited from the practices of Sunnybrook psychiatrists. Subjects will undergo either: i) VR RT + rTMS (n = 17) or ii) VR sham + rTMS (n = 17). Each treatment session involves: 12-15 min VR viewing, 15 min descriptive and imaginal recounting followed immediately by 3 min rTMS delivery with iTBS to the left DLPFC. The study will proceed according to the schedule laid out below. Both patients and treating team will be aware of all treatment parameters at all times.
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Peter Giacobbe, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06178731
- Sponsor's protocol ID
- 5159
- Status last verified
- Dec 2023
- First submitted
- 1 Dec 2023
- Last updated
- 21 Dec 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Virtual Reality Reward Training and Transcranial Magnetic Stimulation for Depression
- ClinicalTrials.gov ID
- NCT06178731
- Acronym / sponsor ID
- 5159
- Conditions
- Major Depressive Disorder
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 29 Oct 2021 (actual)
- Primary completion
- 29 Oct 2024 (estimated)
- Study completion
- 29 Oct 2024 (estimated)
- First posted
- 21 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Anhedonia is a core feature of major depressive disorder (MDD) (DSM-5). Functional magnetic resonance imaging (fMRI) studies have associated anhedonia in MDD with altered frontostriatal activity and functional connectivity relative to controls. Conversely, antidepressant treatment is associated with increased ability for patients with MDD to sustain frontostriatal activity in a manner predictive of decrease in anhedonia and gains in daily positive affect. Novel interventions are needed to address anhedonia. Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) has been shown to activate striatal reward circuits. Positive Affect Treatment (PAT) was developed to treat deficits in reward processing; a critical skill patients are trained on in PAT involves recounting and savouring of positive experiences. However, amotivation impedes some patients from engaging in positive activities, prompting the development of virtual reality reward training (VR RT) for this skill. Evidence is building that brain state at the time of rTMS impacts its therapeutic effect. For example, imaginal exposure and individualized symptom provocation just prior to rTMS enhances its therapeutic effect on post-traumatic stress disorder and obsessive-compulsive disorder, respectively. It is unknown whether VR RT can augment rTMS for MDD and if so whether it is mediated by enhancing changes in frontostriatal activity or functional connectivity.
The current study is significant for multiple reasons. As mentioned, there is a paucity of effective treatments for anhedonia and this study may inform development of a novel treatment strategy that harnesses findings from affective neuroscience. Recent economic analysis suggests that rTMS can be more cost-effective than pharmacotherapy or ECT for treatment-resistant depression (Ontario Health, 2021). Our findings will provide insight on ways to synergize specific psychotherapeutic techniques with targeted stimulation of brain circuits to more effectively treat subtypes of depression.
Detailed description
This is a non-blinded, randomized sham-controlled trial for effectiveness and feasibility of virtual reward reality training and rTMS for MDD with two arms. Patients with MDD who meet inclusion and exclusion criteria will be identified and recruited from the practices of Sunnybrook psychiatrists. Subjects will undergo either: i) VR RT + rTMS (n = 17) or ii) VR sham + rTMS (n = 17). Each treatment session involves: 12-15 min VR viewing, 15 min descriptive and imaginal recounting followed immediately by 3 min rTMS delivery with iTBS to the left DLPFC. The study will proceed according to the schedule laid out below. Both patients and treating team will be aware of all treatment parameters at all times.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a non-blinded, randomized sham-controlled trial for effectiveness and feasibility of virtual reward reality training and rTMS for MDD with two arms. Patients with MDD who meet inclusion and exclusion criteria will be identified and recruited from the practices of Sunnybrook psychiatrists. Subjects will undergo either: i) VR RT + rTMS (n = 17) or ii) VR sham + rTMS (n = 17). Each treatment session involves: 12-15 min VR viewing, 15 min descriptive and imaginal recounting followed immediately by 3 min rTMS delivery with iTBS to the left DLPFC. The study will proceed according to the schedule laid out below. Both patients and treating team will be aware of all treatment parameters at all times.
| Arm | Type | Receives |
|---|---|---|
| Virtual reality + rTMS | Experimental | Device: rTMS, Other: Virtual RealityEach treatment session involves: 12-15 min VR viewing, 15 min descriptive and imaginal recounting followed immediately by 3 min rTMS delivery with iTBS to the left DLPFC. |
| Virtual reality sham + rTMS | Sham comparator | Device: rTMS, Other: Virtual RealityEach treatment session involves: 12-15 min VR viewing, 15 min descriptive and imaginal recounting followed immediately by 3 min rTMS delivery with iTBS to the left DLPFC. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 1. Female or male patients between ages 18-65 2. Diagnosis of major depressive disorder as defined by the Diagnostic and Statistical Manual fifth edition (DSM-5) 3. Hamilton Rating Scale for Depression (17-item) score of at least 16 4. Clinically significant anhedonia as defined by a Smith-Hamilton Pleasure Scale (SHAPS) score of at least 20 (Krystal et al., 2020) 5. On a stable antidepressant regimen for at least 4 weeks before treatment which can continue during treatment and agreement to not make changes or additions to psychotropic medications during the course of their participation in the study 6. Ability to provide informed consent and comply with all testing, follow-ups and study appointments and protocols
Key exclusion criteria (13 listed)
- Any past or current evidence of psychosis or mania
- Active neurologic disease
- Any lifetime history of seizures
- Alcohol or substance dependence or abuse in the last 6 months, excluding caffeine and nicotine
- Current active suicidal ideation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rTMS3 min rTMS delivery with iTBS to the left DLPFC | Device | Virtual reality + rTMS, Virtual reality sham + rTMS |
| Virtual Reality2-15 min VR viewing, 15 min descriptive and imaginal recounting | Other | Virtual reality + rTMS, Virtual reality sham + rTMS |
Primary outcome
The Hamilton Depression Rating Scale
Time frame: up to 4 weeks after treatment
Mood symptoms, higher scores mean worse outcome. Min = 0, Max = 52
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rTMS and Virtual Reality in people with Major Depressive Disorder, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Peter Giacobbe, MD, MSc, BSc (416-480-4085, peter.giacobbe@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Hamilton Depression Rating Scale (time frame: up to 4 weeks after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2023.