Major Depressive DisorderNCT06163625
The Impact of Working Memory and Reward Markers on DLPFC Activity in Treatment-resistant Depression
A study testing Repetitive Transcranial Magnetic Stimulation, Research Interview, Questionnaires and Brain Scan in people with Major Depressive Disorder and Treatment Resistant Depression, run by Unity Health Toronto at 1 site in Canada.
Trial summary
Major Depressive Disorder (MDD) is a very common illness that is usually treated with antidepressant medication. Depression can be caused by many things such as childhood experiences, genetics, and changes in the way the body and brain function. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder, Treatment Resistant Depression
- What is being tested?
- Repetitive Transcranial Magnetic Stimulation, Research Interview, Questionnaires and Brain Scan
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2025to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Depressed Participants:
- Between the ages of 18 and 65 years old.
- Capable of giving voluntary and informed consent.
- Fluent in English.
- Meet Diagnostic and Statistical Manual criteria for single or recurrent Major Depressive Disorder (current major depressive episode), confirmed via the Mini-International Neuropsychiatric Interview (MINI).
- Moderate to severe depression severity, defined as a 17-item Hamilton Depression Rating Scale260 score ≥ 18.
Show all 17Show fewer
- Have failed to achieve a clinical response to an adequate dose of an antidepressant based in an Antidepressant Treatment History Form (ATHF) score ≥ 3 in the current episode, or have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (AHTF = 1 or 2)
- Have had no initiation or dose change in any psychotropic medication in the four weeks prior to screening.
- If participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study.
- Can adhere to the study schedule.
- Nondepressed Participants:
- Between the ages of 18 and 65 years old.
- Capable of giving voluntary and informed consent.
- Fluent in English.
- No current or previous history of psychiatric diagnoses.
- Absent/non-clinical depression severity, defined as a 17-item Hamilton Depression Rating Scale260 < 8.
- No history of antidepressant use, as measured by the ATHF.
Who cannot join
- All Participants:
- Are pregnant/lactating.
- Acute suicidality, defined as a score >3 on the 17-item Hamilton Depression Rating Scale, Item #3.
- A MINI-confirmed diagnosis of bipolar disorder, or another comorbidity (e.g., obsessive-compulsive disorder, post-traumatic stress disorder) that is primary in severity and disability relative to their MDD.
- Other major medical comorbidities requiring immediate investigation or treatment, cardiac pacemaker, or implanted medication pump.
- Lifetime history of psychosis, including schizophrenia, schizoaffective disorder, delusional disorder, or current psychotic symptoms.
Show all 11Show fewer
- Drug abuse or dependence within the last 6 months, excluding caffeine and nicotine.
- Contraindication to receiving the rTMS (e.g. history of seizure, cochlear implants, benzodiazepine use (lorazepam or equivalent daily dose >2mg daily), cardiac pacemaker, implanted neurostimulator, significant head trauma with loss of consciousness for greater than or equal to 5 minutes).
- Electroconvulsive therapy (ECT) within the current depressive episode.
- Presence of contraindications for MRI, including metallic implants.
- Have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of seizure except those therapeutically induced by ECT, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, dementia, significant head trauma with loss of consciousness for greater than or equal to 5 minutes.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Unity Health Toronto
Toronto, Ontario, M5B1M8
Katharine Dunlop, PhD, 416-864-6060 ext. 4078, katharine.dunlop@unityhealth.to
About this study
Major Depressive Disorder (MDD) is a very common illness that is usually treated with antidepressant medication. Depression can be caused by many things such as childhood experiences, genetics, and changes in the way the body and brain function. For those with depression where medication and psychotherapy have limited benefit, repetitive transcranial magnetic stimulation (rTMS) is an effective treatment. rTMS is a treatment that involves stimulating certain areas of the brain with magnetic field pulses. Over time, the magnetic field pulses can gradually change the activity level of the stimulated brain region. This can be helpful in treating some kinds of psychiatric and neurological disorder, including MDD.
It is not fully known how rTMS changes brain activity to improve symptoms of depression. However, certain brain areas responsible for behaviours impacted by depression are underactive in those with depression. One of those brain regions called the dorsolateral prefrontal cortex (DLPFC), and the investigators will target this region using rTMS. By increasing the activity of these regions, rTMS could potentially improve depression symptoms. For participants receiving rTMS, the investigators will be using the participant's brain scan to better understand brain activity of the brain region stimulated by rTMS before and after treatment.
In this study, the investigators will be collecting detailed information about participants' psychiatric history and depression symptoms, as well as brain scans and saliva samples. The saliva samples will undergo proteomic (having to do with proteins) analyses to identify biological markers ("biomarkers": biological features (e.g.: gene, protein) that can be measured to indicate factors related to rTMS response. The investigators' goal is to use this information to help us understand whether improvement to rTMS depends on brain activity or proteomic factors localized to two specific behaviours impacted by depression: reward processing and working memory (the capacity to hold information temporarily, such as holding a person's address in mind while listening to instructions about how to get there).
- Being tested
- Repetitive Transcranial Magnetic Stimulation, Research Interview, Questionnaires, Brain Scan, Saliva Samples
- Medical subject headings
- Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive Transcranial Magnetic StimulationDevice
For those with depression where medication and psychotherapy have limited benefit, repetitive transcranial magnetic stimulation (rTMS) is an effective treatment. rTMS is a treatment that involves stimulating certain areas of the brain with magnetic field pulses. Over time, the magnetic field pulses can gradually change the activity level of the stimulated brain region. This can be helpful in treating some kinds of psychiatric and neurological disorder, including MDD.
Research Interview, QuestionnairesBehavioural
Research Interview: A study team member will meet the participant to ask questions regarding the degree of depression at the beginning of the study. This interview will take approximately 30 minutes.
Research Questionnaires: A study team member will ask the participant to complete questionnaires assessing the severity of the participant's depression, daily activities, personality/traits, and quality of life. Questionnaires will be completed via pen and paper at each visit. These questionnaires will take approximately 90 minutes to complete.
Brain ScanBehavioural
The participant will be asked to undergo a magnetic resonance imaging (MRI) scan to look at the structure and function of their brain. The functional MRI measures the level of blood flow to areas of the brain associated with mood and behaviour, and the participant will be asked to complete two behavioural games while they are in the scanner. During the scan, the participant will be required to lie on a table within the cylindrical tube of the MRI scanner in order to complete the scan. This will result in limited movement for the duration of the scan. The scan will take approximately 60 minutes, and there will be a recovery period for 40 minutes. The participant will be given instructions about these tasks outside of the scanner. This brain scan will happen at St. Michael's Hospital.
Saliva SamplesBiological
The participant will be asked to provide six 1mL saliva samples during the MRI scan and recovery period so that the investigators can measure molecular markers associated with depression. In order to provide the sample, the investigators will collect their saliva using a cotton swab and test tube. Each sample should take no more than 5 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Depression Group | Experimental | Not described Receives: Device: Repetitive Transcranial Magnetic Stimulation; Behavioral: Research Interview, Questionnaires; Behavioral: Brain Scan; Biological: Saliva Samples |
| Control Group | Other | Not described Receives: Behavioral: Research Interview, Questionnaires; Behavioral: Brain Scan; Biological: Saliva Samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hamilton Rating Scale for Depression
Measured: Week 0 to End of Treatment (up to 8 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2023
- Study startJan 2025 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (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 Unity Health TorontoThe 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06163625
- Sponsor's protocol ID
- 22-225
- Status last verified
- May 2024
- First submitted
- 22 Nov 2023
- Last updated
- 19 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Working Memory and Reward Markers on DLPFC Activity in Treatment-resistant Depression
- ClinicalTrials.gov ID
- NCT06163625
- Acronym / sponsor ID
- 22-225
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Study start
- Jan 2025 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 11 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.
Major Depressive Disorder (MDD) is a very common illness that is usually treated with antidepressant medication. Depression can be caused by many things such as childhood experiences, genetics, and changes in the way the body and brain function. For those with depression where medication and psychotherapy have limited benefit, repetitive transcranial magnetic stimulation (rTMS) is an effective treatment. rTMS is a treatment that involves stimulating certain areas of the brain with magnetic field pulses. Over time, the magnetic field pulses can gradually change the activity level of the stimulated brain region. This can be helpful in treating some kinds of psychiatric and neurological disorder, including MDD.
It is not fully known how rTMS changes brain activity to improve symptoms of depression. However, certain brain areas responsible for behaviours impacted by depression are underactive in those with depression. One of those brain regions called the dorsolateral prefrontal cortex (DLPFC), and the investigators will target this region using rTMS. By increasing the activity of these regions, rTMS could potentially improve depression symptoms. For participants receiving rTMS, the investigators will be using the participant's brain scan to better understand brain activity of the brain region stimulated by rTMS before and after treatment.
In this study, the investigators will be collecting detailed information about participants' psychiatric history and depression symptoms, as well as brain scans and saliva samples. The saliva samples will undergo proteomic (having to do with proteins) analyses to identify biological markers ("biomarkers": biological features (e.g.: gene, protein) that can be measured to indicate factors related to rTMS response. The investigators' goal is to use this information to help us understand whether improvement to rTMS depends on brain activity or proteomic factors localized to two specific behaviours impacted by depression: reward processing and working memory (the capacity to hold information temporarily, such as holding a person's address in mind while listening to instructions about how to get there).
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Depression Group | Experimental | Device: Repetitive Transcranial Magnetic Stimulation, Behavioral: Research Interview, Questionnaires, Behavioral: Brain Scan, Biological: Saliva Samples |
| Control Group | Other | Behavioral: Research Interview, Questionnaires, Behavioral: Brain Scan, Biological: Saliva Samples |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Between the ages of 18 and 65 years old.
- Capable of giving voluntary and informed consent.
- Fluent in English.
- Meet Diagnostic and Statistical Manual criteria for single or recurrent Major Depressive Disorder (current major depressive episode), confirmed via the Mini-International Neuropsychiatric Interview (MINI).
- Moderate to severe depression severity, defined as a 17-item Hamilton Depression Rating Scale260 score ≥ 18.
Key exclusion criteria (11 listed)
- Are pregnant/lactating.
- Acute suicidality, defined as a score >3 on the 17-item Hamilton Depression Rating Scale, Item #3.
- A MINI-confirmed diagnosis of bipolar disorder, or another comorbidity (e.g., obsessive-compulsive disorder, post-traumatic stress disorder) that is primary in severity and disability relative to their MDD.
- Other major medical comorbidities requiring immediate investigation or treatment, cardiac pacemaker, or implanted medication pump.
- Lifetime history of psychosis, including schizophrenia, schizoaffective disorder, delusional disorder, or current psychotic symptoms.
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 |
|---|---|---|
| Repetitive Transcranial Magnetic StimulationFor those with depression where medication and psychotherapy have limited benefit, repetitive transcranial magnetic stimulation (rTMS) is an effective treatment. rTMS is a treatment that involves stimulating certain areas of the brain with magnetic field pulses. Over time, the magnetic field pulses can gradually change the activity level of the stimulated brain region. This can be helpful in treating some kinds of psychiatric and neurological disorder, including MDD. | Device | Depression Group |
| Research Interview, QuestionnairesResearch Interview: A study team member will meet the participant to ask questions regarding the degree of depression at the beginning of the study. This interview will take approximately 30 minutes. Research Questionnaires: A study team member will ask the participant to complete questionnaires assessing the severity of the participant's depression, daily activities, personality/traits, and quality of life. Questionnaires will be completed via pen and paper at each visit. These questionnaires will take approximately 90 minutes to complete. | Behavioural | Control Group, Depression Group |
| Brain ScanThe participant will be asked to undergo a magnetic resonance imaging (MRI) scan to look at the structure and function of their brain. The functional MRI measures the level of blood flow to areas of the brain associated with mood and behaviour, and the participant will be asked to complete two behavioural games while they are in the scanner. During the scan, the participant will be required to lie on a table within the cylindrical tube of the MRI scanner in order to complete the scan. This will result in limited movement for the duration of the scan. The scan will take approximately 60 minutes, and there will be a recovery period for 40 minutes. The participant will be given instructions about these tasks outside of the scanner. This brain scan will happen at St. Michael's Hospital. | Behavioural | Control Group, Depression Group |
| Saliva SamplesThe participant will be asked to provide six 1mL saliva samples during the MRI scan and recovery period so that the investigators can measure molecular markers associated with depression. In order to provide the sample, the investigators will collect their saliva using a cotton swab and test tube. Each sample should take no more than 5 minutes. | Biological | Control Group, Depression Group |
Primary outcome
Hamilton Rating Scale for Depression
Time frame: Week 0 to End of Treatment (up to 8 weeks)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2024.
- Individual participant dataSharing planned: No
Related trials for Major Depressive Disorder
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repetitive Transcranial Magnetic Stimulation, Research Interview, Questionnaires and Brain Scan in people with Major Depressive Disorder and Treatment Resistant Depression, run by Unity Health Toronto 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 17 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 19 Dec 2024. 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. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hamilton Rating Scale for Depression (time frame: Week 0 to End of Treatment (up to 8 weeks)). 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 19 Dec 2024.