Temporal Interference Stimulation for Depression

(TI Trial)

Overseen By Ilya Demchenko, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Unity Health Toronto

Must not be taking: Psychotropics, Migraine preventives

Disqualifiers: Substance use, Suicidal intent, Psychotic disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 12

Duration: 2 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to explore a new treatment called Temporal Interference (TI) stimulation for individuals with Major Depressive Disorder (MDD) who don't respond well to existing treatments. TI stimulation is a non-invasive technique using electrical currents to target specific brain areas linked to depression. Participants will receive either the actual TI treatment or a sham (inactive) version while watching emotional film clips during the sessions. The trial seeks individuals with moderate to severe depression who haven't recently changed their depression medication. The goal is to determine if TI can be a safe and effective new option for treating depression. As an unphased trial, this study offers a unique opportunity to contribute to pioneering research in depression treatment.

Will I have to stop taking my current medications?

The trial protocol does not clearly specify if you must stop taking your current medications, but it mentions that medications will be reviewed by the responsible doctor. Some medications that could limit the effectiveness of the treatment might be prohibited.

What prior data suggests that Temporal Interference stimulation is safe for treating depression?

Previous research has shown that Temporal Interference (TI) stimulation is safe and well-tolerated in people. One study found that TI stimulation did not harm brain tissue, even at high levels of 15 mA. Another study confirmed that TI stimulation is safe and comfortable, effectively targeting specific brain areas like the hippocampus without causing damage. These findings suggest that TI stimulation could be a safe option for those considering joining a clinical trial for depression treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Temporal Interference (TI) stimulation for depression because it offers a non-invasive approach that could target specific brain regions without affecting surrounding areas. Unlike standard treatments like antidepressants or electroconvulsive therapy, which often have widespread effects and can take weeks to show improvements, TI stimulation uses precise electrical signals to potentially provide quicker and more targeted relief. This technique is designed to minimize side effects and enhance the precision of treatment, making it a promising alternative for those who haven't found success with existing options.

What evidence suggests that Temporal Interference stimulation might be an effective treatment for depression?

Research has shown that Temporal Interference (TI) stimulation, which participants in this trial may receive, might help treat depression. In one study, people with depression experienced a noticeable improvement in mood, with depression scores dropping from 23.36 to 16.16. Another study found that TI stimulation can safely target specific brain areas, like the hippocampus, which helps regulate mood. These findings suggest that TI stimulation could be a promising new treatment for depression. Participants in this trial may also be assigned to a sham stimulation arm, serving as a control to evaluate the effectiveness of TI stimulation. ^{2 6 7 8 9}

Who Is on the Research Team?

Venkat Bhat, MD MSc

Principal Investigator

Unity Health Toronto

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with Major Depressive Disorder (MDD) experiencing a current episode without psychotic features. Participants must have moderate to severe depression, not have changed their psychotropic medication in the last 4 weeks, and be able to follow the study schedule. They need normal thyroid function and pass a safety questionnaire specific to Temporal Interference (TI).

Inclusion Criteria

Be able to adhere to the treatment schedule

Pass the TI adult safety screening questionnaire

Provide written informed consent before initiation of any study-related procedures

Exclusion Criteria

Have a clinically significant laboratory abnormality, in the opinion of one of the principal investigators or study physicians

Have any other condition that, in the opinion of the investigator(s), would adversely affect the subject's ability to complete the study or its measure

Wear a hairstyle or headdress at the time of the stimulation that prevents electrode contact with the scalp or would interfere with the stimulation (e.g., thick or curly hair)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 10 sessions of 130 Hz Temporal Interference stimulation or sham stimulation, delivered daily for 30 minutes

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Sham stimulation
• Temporal Interference stimulation

Trial Overview The trial tests Temporal Interference stimulation—a new type of brain stimulation—against sham (fake) treatment in people with MDD. It involves applying two high-frequency currents that interact at targeted brain locations. The focus is on whether this can safely alter mood-related brain activity.

How Is the Trial Designed?

Group I: Experimental Arm Experimental Treatment 1 Intervention

130Hz TI stimulation (total 30 min) + mood induction paradigm: ramp-up (30 sec) =\> stimulation (130Hz, 2mA per electrode pair, 4mA total, 29 min) =\> ramp-down (30 sec)

Group II: Sham Arm Placebo Group 1 Intervention

Sham stimulation (total 30 min) + mood induction paradigm: ramp-up (30 sec) =\> ramp-down (30 sec) =\> stimulation (130Hz, 0mA, 29 min)

Who Is Running the Clinical Trial?

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

Ryerson University

Collaborator

Trials

77

Recruited

7,800+

Soterix Medical

Industry Sponsor

Trials

12

Recruited

410+

Toronto Metropolitan University

Collaborator

Trials

95

Recruited

19,300+

Beth Israel Deaconess Medical Center

Collaborator

Trials

872

Recruited

12,930,000+

Northeastern University

Collaborator

Trials

103

Recruited

72,600+

Centre for Addiction and Mental Health

Collaborator

Trials

388

Recruited

84,200+

Charite University, Berlin, Germany

Collaborator

Trials

1,071

Recruited

3,739,000+

Published Research Related to This Trial

The pilot study involving 14 depressed participants found that both alternative electrode montages (Fronto-Occipital and Fronto-Cerebellar) for transcranial direct current stimulation (tDCS) were safe and feasible, with no significant adverse effects reported.

The Fronto-Occipital montage showed a promising mood improvement rate of 43.8% after four weeks, suggesting potential efficacy in treating depression, while the Fronto-Cerebellar montage had a lower improvement rate of 15.9%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of alternative transcranial direct current stimulation electrode montages for the treatment of major depression. Ho, KA., Bai, S., Martin, D., et al.[2018]

Low intensity transcranial electrical stimulation (TES) is considered safe, with no serious adverse events reported in over 18,000 sessions across various populations, including healthy individuals and patients with neurological or psychiatric conditions.

While moderate adverse events like skin burns from tDCS are rare, mild adverse events such as headaches and fatigue are more common, and the safety profile is consistent across different age groups and vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Antal, A., Alekseichuk, I., Bikson, M., et al.[2023]

Transcranial direct current stimulation (tDCS) is generally considered a safe treatment for major depressive disorder, with very low side effects reported, making it a viable option for patients.

While meta-analyses indicate some efficacy of tDCS for acute depression with a moderate effect size, its effectiveness is reduced in treatment-resistant cases, suggesting that more research is needed to establish its overall therapeutic value.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

tDCS for the treatment of depression: a comprehensive review. Palm, U., Hasan, A., Strube, W., et al.[2018]

Transcranial direct current stimulation (tDCS) is a promising non-invasive treatment for Major Depression Disorder (MDD) that can modulate cortical excitability for hours after stimulation, potentially addressing the underlying dysfunction in brain networks associated with depression.

Recent pilot studies have shown that optimized tDCS protocols may effectively reduce symptoms of depression, but further research is necessary to determine the best stimulation parameters and which patients are most likely to benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of depression with transcranial direct current stimulation (tDCS): a review. Nitsche, MA., Boggio, PS., Fregni, F., et al.[2022]

The DepressionDC trial is a multicenter study involving 152 patients with major depressive disorder (MDD) who have not responded to SSRIs, testing the efficacy and safety of prefrontal transcranial direct current stimulation (tDCS) as an add-on treatment over 6 weeks.

This trial employs a rigorous triple-blind design and advanced monitoring of tDCS parameters, aiming to determine if tDCS can significantly improve depression scores compared to a sham treatment, while also assessing cognitive safety and other psychopathological outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prefrontal transcranial direct current stimulation (tDCS) as treatment for major depression: study design and methodology of a multicenter triple blind randomized placebo controlled trial (DepressionDC). Padberg, F., Kumpf, U., Mansmann, U., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12162641/

Advances in the application of temporal interference stimulation The results showed that TIS significantly reduced interictal epileptiform discharges (IEDs) and pathological high-frequency oscillations (HFOs).

2. nature.com nature.com/articles/s41593-023-01456-8

Non-invasive temporal interference electrical stimulation of ... We demonstrate the safety and tolerability of TI stimulation in humans, the ability to focally target the stimulation locus to the hippocampus, ...

3. medrxiv.org medrxiv.org/content/10.1101/2024.11.19.24317540v1.full-text

Efficacy and Safety of Transcranial Temporal Interference ... Significant reductions were observed in depressive symptom scores: HAMD decreased from 23.36 to 16.16 (P < 0.0001), QIDS from 13.52 to 9.68 (P < ...

4. biologicalpsychiatryjournal.com biologicalpsychiatryjournal.com/article/S0006-3223(24)00880-1/fulltext

280. Acute Temporal Interference Stimulation of the Left ... Conclusions. Acute temporal interference stimulation yielded comparable neural and behavioral effects to rTMS, with no discernible impact on HAMD-6 scores. This ...

5. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2024.1484593/full

The safety and efficacy of applying a high-current temporal ... Results: Biochemical and neuropsychological tests revealed no significant differences between the groups. Additionally, no epileptic activities ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11638170/

The safety and efficacy of applying a high-current temporal ... Our findings demonstrate that even a high current TI electrical stimulation of 15 mA does not result in brain tissue damage or physiological and ...

7. medrxiv.org medrxiv.org/content/10.1101/2024.11.19.24317540v1

Efficacy and Safety of Transcranial Temporal Interference ... Significant reductions were observed in depressive symptom scores: HAMD decreased from 23.36 to 16.16 (P < 0.0001), QIDS from 13.52 to 9.68 (P < ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT07191392

Intervention Effect of Temporal Interference Stimulation ... The HAMD is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 54. A higher score ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12273462/

Individualized transcranial temporal interference stimulation ... Compared to baseline, patients showed marked improvements in cognitive function and reductions in negative symptoms [29]. Based on these ...