Transcranial Magnetic Stimulation for Depression

(R33 MDD Trial)

AF
Overseen ByAlmaris Figueroa Gonzalez
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how transcranial magnetic stimulation (TMS) affects the brain in people with depression. Researchers aim to determine if changes in the subgenual anterior cingulate cortex (sgACC) can predict improvements in depressive symptoms. Participants will receive either real or sham (fake) TMS treatments over six weeks to compare results. Ideal participants are adults diagnosed with major or persistent depressive disorder who can commit to daily sessions for six weeks. As an Early Phase 1 trial, this research focuses on understanding how TMS works in people, offering participants a chance to contribute to groundbreaking insights.

What prior data suggests that transcranial magnetic stimulation is safe for treating depression?

Research has shown that transcranial magnetic stimulation (TMS) is generally safe for treating depression. Patients usually tolerate it well, as studies have found. For instance, a review of several studies found that TMS significantly reduced depression symptoms without causing severe side effects. Although some studies reported rare cases of serious events like mania and psychosis, these were uncommon.

One study indicated that both standard repetitive TMS (rTMS) and intermittent theta burst stimulation (iTBS) have similar safety levels, showing no major differences in side effects. Concerns about effects on thinking were not supported by the evidence.

Overall, TMS has been used safely and effectively in many patients with depression.12345

Why do researchers think this study treatment might be promising for depression?

Researchers are excited about transcranial magnetic stimulation (TMS) because it offers a non-invasive way to treat depression by directly targeting the brain. Unlike traditional medications that often take weeks to show effectiveness and can have various side effects, TMS uses magnetic fields to stimulate specific brain areas involved in mood regulation. The active intermittent theta burst stimulation (iTBS) being studied is especially promising because it applies this technique more precisely, potentially leading to faster and more effective relief from depressive symptoms. This direct approach could provide a new option for those who haven't found success with standard treatments like antidepressants or psychotherapy.

What evidence suggests that transcranial magnetic stimulation might be an effective treatment for depression?

This trial will compare two forms of transcranial magnetic stimulation (TMS) for treating depression: Active Repetitive Transcranial Magnetic Stimulation (rTMS) and Sham Transcranial Magnetic Stimulation (TMS). Research has shown that TMS can help treat depression, with studies finding significant symptom reduction for some individuals. This treatment uses magnetic fields to stimulate specific brain areas involved in mood regulation. Patients often report feeling better and experiencing fewer symptoms after regular sessions. While results can vary, many have had positive experiences with TMS in managing their depression.6789

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with depression, including persistent depressive disorder. Participants should be able to undergo MRI scans and TMS treatments. People with certain medical or psychiatric conditions that could interfere with the study may not be eligible.

Inclusion Criteria

PHQ-9 score equal to or greater than 10
Availability for the duration of the study
I am between 18 and 65 years old.
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Exclusion Criteria

Current psychosis, mania, or substance use disorder
Implanted medical devices, metallic implants, or drug infusion pumps that are not MRI-safe (e.g., aneurysm clips, defibrillators, or cochlear implants)
History of significant medical events (e.g., stroke, seizures, brain scarring) or neurological/neurodevelopmental conditions (e.g., epilepsy) contraindicating TMS and MRI or affecting brain function and data interpretation
See 14 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Baseline Assessment

Participants undergo baseline MRI session and complete clinical assessments, questionnaires, and cognitive testing

1 week
1 visit (in-person)

Treatment

Participants receive active or sham TMS every weekday for 6 weeks, with MRI scans before, during, and after the intervention

6 weeks
30 visits (in-person)

Follow-up

Participants complete remote follow-up assessments at 1, 6, and 12 months after completion of the blinded intervention

12 months
3 visits (virtual)

Open-label Extension (optional)

Participants assigned to sham who continue to have clinically significant depressive symptoms may be offered an optional open-label active TMS intervention

What Are the Treatments Tested in This Trial?

Interventions

  • Active Repetitive Transcranial Magnetic Stimulation (rTMS)
  • Sham Transcranial Magnetic Stimulation (TMS)

Trial Overview

The study compares active transcranial magnetic stimulation (TMS) to a sham (placebo-like) TMS over 6 weeks. Researchers use brain scans and assessments to see how each treatment affects brain circuits linked to depression and symptoms.

How Is the Trial Designed?

2

Treatment groups

Experimental Treatment

Placebo Group

Group I: Active iTBSExperimental Treatment1 Intervention
Group II: Sham iTBSPlacebo Group1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Desmond Oathes

Lead Sponsor

University of Pennsylvania

Lead Sponsor

Trials
2,118
Recruited
45,270,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials
3,007
Recruited
2,852,000+

Citations

1.

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doing something as you usually do, or being able to do something physically or mentally: He was still an active runner at 55. She's active in state ...

Efficacy and safety of repetitive transcranial magnetic ... - PMC

Meta-analysis showed that active rTMS significantly reduced depression scale scores (SMD = – 0.93, 95% CI = – 1.31 to – 0.55).

Outcome of transcranial magnetic intermittent theta-burst ...

Overall, iTBS is considered an effective, safe and tolerable treatment for depression (Stultz et al., 2020) (Chu et al., 2021).

Connectivity-guided intermittent theta burst versus ...

Two serious adverse events were possibly related to TMS (mania and psychosis). MRI-neuronavigated cgiTBS and rTMS were equally effective in ...

Comparing the Efficacy of fMRI-Guided vs. Standard iTBS ...

Secondary outcomes include remission rate, change in depression, anxiety and anhedonia symptoms, quality of life, and biological measures of heart rate ...

Efficacy and safety of intermittent theta burst stimulation ...

active rTMS targeting the left dorsolateral prefrontal cortex (DLPFC) led to a higher rate of clinical remission and response compared 10.