NCT07188753

Randomized Controlled Trial Testing the Efficacy of Transcranial Magnetic Stimulation by Accelerated & High-dose Theta-burst, Functional Imaging Guided, in the Treatment of Depression in Elderly Subjects With Cognitive Impairment

OLDEP-TBS - Randomized Controlled Trial Testing the Efficacy of Transcranial Magnetic Stimulation by Accelerated & High-dose Theta-burst, Functional Imaging Guided, in the Treatment of Depression in Elderly Subjects With Cognitive Impairment

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 186 (estimated)
• Sponsor: Rennes University Hospital · Academic / Other
• Sex: All
• Age: 65 Years
• Healthy volunteers: Not accepted

Summary

This trial aims at testing a new intensive, personalized functional targeting, transcranial magnetic stimulation technique for elderly patients (aged ≥ 65 years) suffering from a current treatment resistant depressive episode to at least one antidepressant, and suffering from significant secondary cognitive impairment. The intervention will be based on an accelerated neuromodulation technique using intermittent theta bursts (aiTBS) guided by a personalised funcitonal target within the left dorsolateral prefrontal cortex (DLPFC), using the SAINT® technology, which was recently cleared by the FDA.

Detailed description

Depression in older adults is often associated with cognitive impairment. Executive dysfunction exposes patients to poor response to antidepressants, increased risk of relapse and suicide, and greater disability. Depression doubles the risk of developing dementia in later life. Late-onset depression is considered more difficult to treat due to low tolerance to standard antidepressant treatments, which prevents dose optimisation. Late-onset depression is considered more difficult to treat due to poor tolerance to standard antidepressant treatments, which prevents dose optimisation. Furthermore, antidepressants are not optimal for improving cognitive function. Thus, antidepressant therapies are limited in terms of efficacy or tolerance, leading to persistent depressive symptoms and cognitive deficits that impact daily functioning, quality of life, and even independence. Transcranial magnetic stimulation, a focused non-pharmacological antidepressant therapy, is a promising alternative. Several meta-analyses have demonstrated its efficacy as an antidepressant treatment and its potential for treating mild cognitive impairment. However, these studies have encountered certain limitations, such as small sample sizes and heterogeneity. Recently, a randomised controlled trial testing an accelerated form of intermittent theta burst stimulation (aiTBS) in adults with treatment-resistant depression demonstrated a high remission rate of approximately 80% (with effect sizes ranging from \[1.4-1.8\]). This technique has a good tolerance profile. Overall, aiTBS treatment has several potentially beneficial aspects for depression in older adults: efficacy, rapid onset of action, and good tolerability. Such a technique could prevent the negative impact of depression and cognitive impairment on the quality of life and independence of older adults with depression. In this randomised controlled trial (RCT), the investigators aim to test the efficacy of aiTBS treatment guided by functional connectivity at rest in elderly patients suffering from major depressive disorder (MDD) in a major depressive episode (MDE) and cognitive impairment. The investigators hypothesise that active aiTBS treatment will be superior to placebo aiTBS treatment in improving depressive and cognitive symptoms.

Conditions

• Treatment Resistant Depression
• Elderly Depression (≥65y.o.)

Interventions

Type	Name	Description
OTHER	transcranial magnetic stimulation by accelerated & high-dose theta-burst, functional imaging guided, i	Participants will then be treated with 1,800 pulses of iTBS (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds) per session at 90% resting motor threshold and depth-adjustment to the personalized functional target. Each session will last 10 min followed by a 50-minute intersession interval. Ten sessions will be applied per day (18,000 pulses/day) for 5 consecutive days (90,000 total pulses).

Timeline

• Start date: 2025-12-15
• Primary completion: 2031-06-15
• Completion: 2031-12-15
• First posted: 2025-09-23
• Last updated: 2025-09-23