Late Life Depression (LLD)ACT-LLDNCT06854367
Accelerated vs. Conventional Theta Burst Stimulation for Late-life Depression
A study testing TBS in people with Late Life Depression (LLD) and Depression - Major Depressive Disorder, run by Centre for Addiction and Mental Health at 2 sites in Canada.
Trial summary
The purpose of this trial is to compare the treatment efficacy (improvement in depressive symptoms) of accelerated TBS protocol (where participants receive multiple TBS treatments daily) to conventional TBS protocol (where participants receive a single TBS treatment daily) in late life depression. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Late Life Depression (LLD), Depression - Major Depressive Disorder, Depressive Disorder, Treatment-Resistant
- What is being tested?
- TBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 280 participants
- Where
- 2 sitesCanada
- Study dates
- 27 Mar 2025to Dec 2029
- 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- are voluntary and competent to consent to treatment
- are an outpatient
- are ≥ 60 years old
- have a Mini International Neuropsychiatric Interview (MINI 7.0) confirmed diagnosis of MDD, with a current MDE
- have failed to achieve a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of ≥ 3 in the current episode or have failed to tolerate two separate trials of an antidepressant
- have a score ≥ 10 on the Patient Health Questionnaire (PHQ-9)
Show all 9Show fewer
- have had no increase or initiation of any antidepressant or antipsychotic medication in the 4 weeks prior to screening
- are able to adhere to the treatment schedule
- pass the TMS adult safety screening (TASS) questionnaire
Who cannot join
- have a Mini International Neuropsychiatric Interview (MINI 7.0) confirmed diagnosis of substance dependence or abuse within the last 3 months
- have a concomitant major unstable medical illness as determined by one of the study physicians
- have active suicidal intent
- have presumed or probable dementia or clinical evidence of dementia as assessed by Short Blessed Test score ≥ 10
- have a lifetime MINI diagnosis of bipolar I or II disorder, or primary psychotic disorder
- have current psychotic symptoms
Show all 17Show fewer
- have a diagnosis of obsessive compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder), or dysthymia, assessed by a study investigator to be primary and causing greater impairment than MDD
- have a diagnosis of any personality disorder as assessed by a study investigator to be primary and causing greater impairment than MDD
- did not respond to a course of ECT in the current depressive episode
- have received rTMS in the current episode; patients who have had rTMS in a previous episode would be eligible
- have a history of a primary seizure disorder or a seizure associated with an intracranial lesion
- have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed
- have an implanted electronic device that is currently in function such as a defibrillator
- have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview)
- have clinically significant laboratory abnormality, in the opinion of a study investigator
- currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada2 sites, 2 recruiting
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Donguk Jo, 416-480-6100 ext. 61518, donguk.jo@sri.utoronto.ca
Sean M Nestor
- Recruiting
Centre for Addiction and Mental Healh
Toronto, Ontario, M6J 1H1
Elizabeth Clancy, 416-535-8501, elizabeth.clancy@camh.ca
Hyewon (Helen) Lee
About this study
The purpose of this trial is to compare the treatment efficacy (improvement in depressive symptoms) of accelerated TBS protocol (where participants receive multiple TBS treatments daily) to conventional TBS protocol (where participants receive a single TBS treatment daily) in late life depression. In addition, the study also aims to determine if specific patterns of stimulation are more or less effective. To do this, all participants will receive active treatments, but some of the participants in this study will receive accelerated TBS and some will receive once daily TBS.
Read the detailed description
The purpose of this trial is to compare the treatment efficacy (change in MADRS scores) of accelerated TBS to conventional TBS in participants with moderate to severe LLD at 4-weeks following accelerated TBS or following 30 once daily treatments of conventional TBS. Accelerated TBS group will receive 5 treatment sessions per day at approximately 1 hour intervals for 4 consecutive days on week 1 and 2 non-consecutive days on week 2. Conventional TBS group will receive 30 once daily treatment (approximately 6 weeks). Each treatment will consist of either 1) cTBS of right DLPFC followed by iTBS of left DLPFC; or 2) iTBS of left DLPFC.
- Conditions
- Late Life Depression (LLD), Depression - Major Depressive Disorder, Depressive Disorder, Treatment-Resistant, Mood Disorders
- Being tested
- TBS
- Keywords
- Brain stimulation, rTMS, Theta burst stimulation, Accelerated theta burst stimulation
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Mood Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TBSDevice
Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive neurostimulation that uses focused magnetic field pulses to directly stimulate cortical neurons. Theta burst stimulation (TBS) is a briefer form of patterned rTMS that has been shown to be effective against major depressive disorder. Each treatment will consist of either 1) cTBS of right DLPFC followed by iTBS of left DLPFC; or 2) iTBS of left DLPFC.
| Study group | Role | What they receive |
|---|---|---|
| Accelerated TBS | Active comparator | Multiple treatments a day (5 treatments/day) for 4 consecutive days in the first week and 2 non-consecutive days in the second week. Receives: Device: TBS |
| Conventional TBS | Active comparator | Treatment once a day for 30 days (e.g., 5 days a week for 6 weeks) Receives: Device: TBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depression severity
Montgomery Asberg Depression Rating Scale (MADRS) Change
Measured: 6 weeks
Secondary outcomes (12)
Depression severity
17 item Hamilton Depression Rating Scale (HDRS-17) Change
Measured: up to 10 weeks
Depression severity
The Beck Depression Inventory (BDI-II) Change
Measured: up to 10 weeks
Anxiety severity
General Anxiety Disorder-7 (GAD-7) Change
Measured: up to 10 weeks
Suicidal ideation
The Beck Scale for Suicide Ideation (BSS) Change
Measured: up to 10 weeks
Global cognition
Montreal Cognitive Assessment (MoCA) Change
Measured: up to 10 weeks
Executive function
Delis-Kaplan Executive Function System (D-KEFS) Change
Measured: up to 10 weeks
Executive function
NIH Toolbox Flanker Inhibitory Control and Attention Test
Measured: up to 10 weeks
Memory
California Verbal Learning Test- third edition (CVLT-3) Change
Measured: up to 10 weeks
Disability and Functional Impairment
Sheehan Disability Scale (SDS) Change
Measured: up to 10 weeks
Quality of Life Measure
Quality of Life Enjoyment and Satisfaction Scale (Q-LES-Q) change
Measured: up to 10 weeks
Quality of Life Measure
World Health Organization Quality of Life Short Version (WHOQOL-BREF) Change
Measured: up to 10 weeks
Participant Expectancy of Improvement and Preference
Modified Stanford Expectations of Treatment Scale (SETS)
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2025
- Study start27 Mar 2025
- Primary completionNov 2029 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Late Life Depression (LLD)Studies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- Sunnybrook Health Sciences Centre
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06854367
- Sponsor's protocol ID
- CTO4933
- Acronym
- ACT-LLD
- Status last verified
- Oct 2026
- First submitted
- 21 Feb 2025
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Accelerated vs. Conventional Theta Burst Stimulation for Late-life Depression
- ClinicalTrials.gov ID
- NCT06854367
- Acronym / sponsor ID
- ACT-LLD / CTO4933
- Conditions
- Late Life Depression (LLD), Depression - Major Depressive Disorder, Depressive Disorder, Treatment-Resistant, Mood Disorders
- Keywords
- Brain stimulation, rTMS, Theta burst stimulation, Accelerated theta burst stimulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 280 participants (estimated)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- Sunnybrook Health Sciences Centre
- Study start
- 27 Mar 2025 (actual)
- Primary completion
- Nov 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 3 Mar 2025 (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.
The purpose of this trial is to compare the treatment efficacy (improvement in depressive symptoms) of accelerated TBS protocol (where participants receive multiple TBS treatments daily) to conventional TBS protocol (where participants receive a single TBS treatment daily) in late life depression. In addition, the study also aims to determine if specific patterns of stimulation are more or less effective. To do this, all participants will receive active treatments, but some of the participants in this study will receive accelerated TBS and some will receive once daily TBS.
Detailed description
The purpose of this trial is to compare the treatment efficacy (change in MADRS scores) of accelerated TBS to conventional TBS in participants with moderate to severe LLD at 4-weeks following accelerated TBS or following 30 once daily treatments of conventional TBS. Accelerated TBS group will receive 5 treatment sessions per day at approximately 1 hour intervals for 4 consecutive days on week 1 and 2 non-consecutive days on week 2. Conventional TBS group will receive 30 once daily treatment (approximately 6 weeks). Each treatment will consist of either 1) cTBS of right DLPFC followed by iTBS of left DLPFC; or 2) iTBS of left DLPFC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Accelerated TBS | Active comparator | Device: TBSMultiple treatments a day (5 treatments/day) for 4 consecutive days in the first week and 2 non-consecutive days in the second week. |
| Conventional TBS | Active comparator | Device: TBSTreatment once a day for 30 days (e.g., 5 days a week for 6 weeks) |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- are voluntary and competent to consent to treatment
- are an outpatient
- are ≥ 60 years old
- have a Mini International Neuropsychiatric Interview (MINI 7.0) confirmed diagnosis of MDD, with a current MDE
- have failed to achieve a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of ≥ 3 in the current episode or have failed to tolerate two separate trials of an antidepressant
Key exclusion criteria (17 listed)
- have a Mini International Neuropsychiatric Interview (MINI 7.0) confirmed diagnosis of substance dependence or abuse within the last 3 months
- have a concomitant major unstable medical illness as determined by one of the study physicians
- have active suicidal intent
- have presumed or probable dementia or clinical evidence of dementia as assessed by Short Blessed Test score ≥ 10
- have a lifetime MINI diagnosis of bipolar I or II disorder, or primary psychotic disorder
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 |
|---|---|---|
| TBSRepetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive neurostimulation that uses focused magnetic field pulses to directly stimulate cortical neurons. Theta burst stimulation (TBS) is a briefer form of patterned rTMS that has been shown to be effective against major depressive disorder. Each treatment will consist of either 1) cTBS of right DLPFC followed by iTBS of left DLPFC; or 2) iTBS of left DLPFC. | Device | Accelerated TBS, Conventional TBS |
Primary outcome
Depression severity
Time frame: 6 weeks
Montgomery Asberg Depression Rating Scale (MADRS) Change
12 secondary outcomes
Depression severity
Time frame: up to 10 weeks
Depression severity
Time frame: up to 10 weeks
Anxiety severity
Time frame: up to 10 weeks
Suicidal ideation
Time frame: up to 10 weeks
Global cognition
Time frame: up to 10 weeks
Executive function
Time frame: up to 10 weeks
Executive function
Time frame: up to 10 weeks
Memory
Time frame: up to 10 weeks
Disability and Functional Impairment
Time frame: up to 10 weeks
Quality of Life Measure
Time frame: up to 10 weeks
Quality of Life Measure
Time frame: up to 10 weeks
Participant Expectancy of Improvement and Preference
Time frame: Baseline
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 22 Oct 2026.
- Individual participant dataSharing planned: Undecided
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TBS in people with Late Life Depression (LLD) and Depression - Major Depressive Disorder, run by Centre for Addiction and Mental Health at 2 sites 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 9 inclusion and 17 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 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Depression severity (time frame: 6 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 22 Oct 2026.