Depressive SymptomsNCT02472470
Efficacy and Biological Targets of Response to rTMS Therapy in Youth Depression
A study testing rTMS in people with Depressive Symptoms, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial summary
Youth depression is a debilitating disorder that exacts enormous social, economic and personal cost. Unfortunately, treatments which are conventionally used to treat adult depression have often modest to no efficacy in youth and have side effects. Read more about this study
- Who is it for?
- Ages 16 to 24 years
- Conditions the study is for
- Depressive Symptoms
- What is being tested?
- rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2015to May 2017
- 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 16 to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- outpatients
- between the ages of 16 and 24
- competent to consent to study participation
- Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of MDD single or recurrent
- no change in treatment (psychotherapy or medication) for at least four weeks prior to participation in the study
- HRSD-17 score of 20 and higher
- at least one failed/refused/intolerant to antidepressant trial in the current episode as determined by Antidepressant Treatment History Form (ATHF)
- No safety concerns endorsed on TMS Screening and Information Form
Who cannot join
- lifetime MINI diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, delusional disorder, current psychotic symptoms, post traumatic stress disorder, obsessive compulsive disorder, autism spectrum disorder, a history of epilepsy or any other major neurological disorder
- history of substance use disorders (moderate to severe) within the last 3 months as determined by MINI
- concomitant major unstable medical illness
- acutely suicidal or high risk for suicide as assessed by a study psychiatrist
- not eligible to receive TMS or MRI as indicated by TMS Screening and Information Form
- a change in treatment status during the study trial that will be considered a confound to the study. This includes change in medication or Cognitive Behavioral Therapy, each reviewed case by case by the study psychiatrists.
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- medications that are considered a confound to the study including benzodiazepines, antipsychotics, mood stabilizers, stimulants and anticonvulsants.
- missing more than 20% of the treatment sessions consecutively (i.e., 2 sessions in a row) or 40% (i.e., 4 sessions) within two weeks
- have failed brain stimulation in the past
Trial locations and contacts
1 site in 1 country.
About this study
Youth depression is a debilitating disorder that exacts enormous social, economic and personal cost. Unfortunately, treatments which are conventionally used to treat adult depression have often modest to no efficacy in youth and have side effects. Thus, there is a tremendous imperative to develop new treatments for youth depression. Investigators propose to examine the efficacy of a short form of repetitive transcranial magnetic stimulation (rTMS) for youth depression and examine its biological targets. This will be the first study examining the efficacy of a short rTMS protocol in youth diagnosed with depression who fail responding to or are intolerable to antidepressants. If the results are positive, investigators will have identified a novel treatment that may be both more efficacious, better tolerated and more acceptable treatment for youth depression. Finally, identifying the biological mechanisms leading to treatment efficacy will lead to more personalized treatments for youth depression and will be groundbreaking vis à vis understanding the mechanisms involved in this illness.
Read the detailed description
The highest rates of depression are reported in youth 16-24 years of age and youth depression is a significant source of burden to the individual, their families, and to society. Unfortunately, current treatments (e.g., selective serotonin reuptake inhibitors), which are conventionally used to treat depression often have modest and sometimes no efficacy in youth. Also, accumulating evidence suggests that these medications may increase suicidal thoughts in adolescents and young adults below the age of 24. In addition to pharmacological treatments, cognitive behavioral therapy (CBT) has been used alone or in combination with medications for treating depression in this age group. Although randomized controlled trials and practice guidelines support the use of CBT alone and CBT with an antidepressant medication for adolescent depression, a large minority of adolescents do not respond to either treatment approaches.Thus, there is a tremendous imperative to develop new treatments for youth depression.
Investigators propose to examine the efficacy of repetitive transcranial magnetic stimulation (rTMS) for youth depression. There are several reasons for pursuing this treatment: 1) rTMS applied to the dorsolateral prefrontal cortex (DLPFC), a cortical region implicated in pathophysiology of depression, is a safe and FDA approved treatment for adults with medication-resistant depression; 2) Young age is suggested to be a good predictor of response to rTMS treatment; 3) rTMS trials in adolescence and youth with medication resistant depression provide evidence that rTMS is a safe efficacious and well tolerated treatment for adolescents that does not increase suicidal thoughts. Additionally, recently rTMS parameter developments such as theta burst stimulation (i.e., TBS) provide compelling evidence for efficacy in less of the time it takes to administer conventional rTMS, thus lowering the overall costs and increasing the number of patients that can be treated.
It is imperative that research investigate treatment related biological mechanisms, such that increases in understanding can lead to enhanced efficacy. Investigators will utilize a novel and powerful in vivo brain mapping technique of TMS combined with electroencephalography (TMS-EEG) that permits non-invasive assessment of inhibitory, connectivity and plasticity mechanisms from the DLPFC. The pathophysiology of depression has been linked to impairment in neural plasticity and connectivity and neural and behavioral inhibition - mechanisms that can be measured through TMS-EEG and maybe changed by TBS treatment. Therefore, investigating the association between TBS-related changes in plasticity, connectivity and inhibition may be key to understanding both the treatment mechanisms involved in youth depression and predictors of treatment response in this disorder.
Therefore the specific aims in this study are twofold:
- To examine the efficacy of TBS applied to the DLPFC for youth depression, and
- To identify biological targets and predictors of response to TBS applied to the DLPFC for youth depression.
- Conditions
- Depressive Symptoms
- Being tested
- rTMS
- Keywords
- rTMS, Depression, Youth, TBS, Brain Stimulation, Electrophysiology, Imaging
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMSDevice
Also called TBS
Participants will receive 10 active TBS rTMS sessions once daily on weekdays for 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | intermitten TBS (iTBS) rTMS applied to the left Dorsolateral Prefrontal Cortex (DLPFC) + continuous TBS (cTBS) rTMS applied to the right DLPFC. The order will be counterbalanced. Administration of this treatment takes roughly 10 minutes. This treatment will be applied daily, 5 days/week, for 2 weeks. Receives: Device: rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depressive Symptoms as Measured by HRSD-17
Outcome measure is measured by a change in the HRSD-17 score from baseline to week 1 and week 3. A 50% improvement in the score is considered response to rTMS
Measured: Baseline (before treatment trial starts), week 1 (after 5 days of treatment), and week 3 (within a week after the end of the 2-week treatment trial)
Secondary outcomes (2)
Beck Depression Inventory-II (BDI-II)
Measured: Baseline (before treatment trial starts), week 1 (after 5 days of treatment), and week 3 (within a week after the end of the 2-week treatment trial)
Children's Depression Rating Scale, revised-version (CDRS-R)
Only in participants under 18 years of age
Measured: Baseline (before treatment trial starts), week 1 (after 5 days of treatment), and week 3 (within a week after the end of the 2-week treatment trial)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2015 (estimated)
- Study startJun 2015
- Primary completionMay 2017
- Study completionMay 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Depressive SymptomsStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Faranak Farzan, Centre for Addiction and Mental Health
- Investigators
- Faranak Farzan, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02472470
- Sponsor's protocol ID
- # 076/2014-01
- Status last verified
- Oct 2017
- First submitted
- 10 Jun 2015
- Last updated
- 24 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Dhami P, Moreno S, Croarkin PE, Blumberger DM, Daskalakis ZJ, Farzan F. Baseline markers of cortical excitation and inhibition predict response to theta burst stimulation treatment for youth depression. Sci Rep. 2023 Nov 4;13(1):19115. doi: 10.1038/s41598-023-45107-1.
PubMed 37925557Dhami P, Atluri S, Lee J, Knyahnytska Y, Croarkin PE, Blumberger DM, Daskalakis ZJ, Farzan F. Neurophysiological markers of response to theta burst stimulation in youth depression. Depress Anxiety. 2021 Feb;38(2):172-184. doi: 10.1002/da.23100. Epub 2020 Oct 1.
PubMed 33001549
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Biological Targets of Response to rTMS Therapy in Youth Depression
- ClinicalTrials.gov ID
- NCT02472470
- Acronym / sponsor ID
- # 076/2014-01
- Conditions
- Depressive Symptoms
- Keywords
- rTMS, Depression, Youth, TBS, Brain Stimulation, Electrophysiology, Imaging
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- May 2017 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 15 Jun 2015 (estimated)
- 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.
Youth depression is a debilitating disorder that exacts enormous social, economic and personal cost. Unfortunately, treatments which are conventionally used to treat adult depression have often modest to no efficacy in youth and have side effects. Thus, there is a tremendous imperative to develop new treatments for youth depression. Investigators propose to examine the efficacy of a short form of repetitive transcranial magnetic stimulation (rTMS) for youth depression and examine its biological targets. This will be the first study examining the efficacy of a short rTMS protocol in youth diagnosed with depression who fail responding to or are intolerable to antidepressants. If the results are positive, investigators will have identified a novel treatment that may be both more efficacious, better tolerated and more acceptable treatment for youth depression. Finally, identifying the biological mechanisms leading to treatment efficacy will lead to more personalized treatments for youth depression and will be groundbreaking vis à vis understanding the mechanisms involved in this illness.
Detailed description
The highest rates of depression are reported in youth 16-24 years of age and youth depression is a significant source of burden to the individual, their families, and to society. Unfortunately, current treatments (e.g., selective serotonin reuptake inhibitors), which are conventionally used to treat depression often have modest and sometimes no efficacy in youth. Also, accumulating evidence suggests that these medications may increase suicidal thoughts in adolescents and young adults below the age of 24. In addition to pharmacological treatments, cognitive behavioral therapy (CBT) has been used alone or in combination with medications for treating depression in this age group. Although randomized controlled trials and practice guidelines support the use of CBT alone and CBT with an antidepressant medication for adolescent depression, a large minority of adolescents do not respond to either treatment approaches.Thus, there is a tremendous imperative to develop new treatments for youth depression.
Investigators propose to examine the efficacy of repetitive transcranial magnetic stimulation (rTMS) for youth depression. There are several reasons for pursuing this treatment: 1) rTMS applied to the dorsolateral prefrontal cortex (DLPFC), a cortical region implicated in pathophysiology of depression, is a safe and FDA approved treatment for adults with medication-resistant depression; 2) Young age is suggested to be a good predictor of response to rTMS treatment; 3) rTMS trials in adolescence and youth with medication resistant depression provide evidence that rTMS is a safe efficacious and well tolerated treatment for adolescents that does not increase suicidal thoughts. Additionally, recently rTMS parameter developments such as theta burst stimulation (i.e., TBS) provide compelling evidence for efficacy in less of the time it takes to administer conventional rTMS, thus lowering the overall costs and increasing the number of patients that can be treated.
It is imperative that research investigate treatment related biological mechanisms, such that increases in understanding can lead to enhanced efficacy. Investigators will utilize a novel and powerful in vivo brain mapping technique of TMS combined with electroencephalography (TMS-EEG) that permits non-invasive assessment of inhibitory, connectivity and plasticity mechanisms from the DLPFC. The pathophysiology of depression has been linked to impairment in neural plasticity and connectivity and neural and behavioral inhibition - mechanisms that can be measured through TMS-EEG and maybe changed by TBS treatment. Therefore, investigating the association between TBS-related changes in plasticity, connectivity and inhibition may be key to understanding both the treatment mechanisms involved in youth depression and predictors of treatment response in this disorder.
Therefore the specific aims in this study are twofold:
- To examine the efficacy of TBS applied to the DLPFC for youth depression, and
- To identify biological targets and predictors of response to TBS applied to the DLPFC for youth depression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Device: rTMSintermitten TBS (iTBS) rTMS applied to the left Dorsolateral Prefrontal Cortex (DLPFC) + continuous TBS (cTBS) rTMS applied to the right DLPFC. The order will be counterbalanced. Administration of this treatment takes roughly 10 minutes. This treatment will be applied daily, 5 days/week, for 2 weeks. |
Who may qualify
- Ages
- 16 to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- outpatients
- between the ages of 16 and 24
- competent to consent to study participation
- Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of MDD single or recurrent
- no change in treatment (psychotherapy or medication) for at least four weeks prior to participation in the study
Key exclusion criteria (9 listed)
- lifetime MINI diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, delusional disorder, current psychotic symptoms, post traumatic stress disorder, obsessive compulsive disorder, autism spectrum disorder, a history of epilepsy or any other major neurological disorder
- history of substance use disorders (moderate to severe) within the last 3 months as determined by MINI
- concomitant major unstable medical illness
- acutely suicidal or high risk for suicide as assessed by a study psychiatrist
- not eligible to receive TMS or MRI as indicated by TMS Screening and Information Form
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 |
|---|---|---|
| rTMSAlso: TBSParticipants will receive 10 active TBS rTMS sessions once daily on weekdays for 2 weeks. | Device | Treatment |
Primary outcome
Depressive Symptoms as Measured by HRSD-17
Time frame: Baseline (before treatment trial starts), week 1 (after 5 days of treatment), and week 3 (within a week after the end of the 2-week treatment trial)
Outcome measure is measured by a change in the HRSD-17 score from baseline to week 1 and week 3. A 50% improvement in the score is considered response to rTMS
2 secondary outcomes
Beck Depression Inventory-II (BDI-II)
Time frame: Baseline (before treatment trial starts), week 1 (after 5 days of treatment), and week 3 (within a week after the end of the 2-week treatment trial)
Children's Depression Rating Scale, revised-version (CDRS-R)
Time frame: Baseline (before treatment trial starts), week 1 (after 5 days of treatment), and week 3 (within a week after the end of the 2-week treatment trial)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2017.
- Derived from this study: PubMed 37925557Dhami P, Moreno S, Croarkin PE, Blumberger DM, Daskalakis ZJ, Farzan F. Baseline markers of cortical excitation and inhibition predict response to theta burst stimulation treatment for youth depression. Sci Rep. 2023 Nov 4;13(1):19115. doi: 10.1038/s41598-023-45107-1.
- Derived from this study: PubMed 33001549Dhami P, Atluri S, Lee J, Knyahnytska Y, Croarkin PE, Blumberger DM, Daskalakis ZJ, Farzan F. Neurophysiological markers of response to theta burst stimulation in youth depression. Depress Anxiety. 2021 Feb;38(2):172-184. doi: 10.1002/da.23100. Epub 2020 Oct 1.
- Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teachingLink provided by the sponsor.
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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.
Faranak Farzan principal investigator
Centre for Addiction and Mental Health
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 in people with Depressive Symptoms, run by Centre for Addiction and Mental Health 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 8 inclusion and 9 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: finished, as of the sponsor's last update on 24 Oct 2017. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Depressive Symptoms as Measured by HRSD-17 (time frame: Baseline (before treatment trial starts), week 1 (after 5 days of treatment), and week 3 (within a week after the end of the 2-week treatment trial)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02472470, which also lists 2 linked publications.
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 24 Oct 2017.