SAINT Stimulation for Depression

Recruiting at 3 trial locations

Overseen By Anthony Purgianto, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Magnus Medical

Must not be taking: Ketamine, ECT

Disqualifiers: Anxiety, Bipolar, OCD, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 1 week

2 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a device that uses magnetic pulses to help adults with severe depression and suicidal thoughts who haven't improved with standard treatments. The device targets a specific brain area to improve mood and reduce suicidal thoughts. This method has shown promising results as an alternative to other treatments for severe depression.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should not have used rapid-acting antidepressants like ketamine recently. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the SAINT Stimulation treatment for depression?

Research shows that transcranial magnetic stimulation (TMS), a technique similar to SAINT Stimulation, can reduce symptoms of major depressive disorder. Studies indicate that TMS is more effective than a placebo, although the effect can be weak, and the effectiveness may depend on targeting the right brain area. ^{1 2 3 4 5}

Is SAINT Stimulation generally safe for humans?

SAINT Stimulation, also known as repetitive transcranial magnetic stimulation (rTMS), is generally considered safe for treating depression, with a low risk of seizures (about one in 1,000 patients). Some patients may find the treatment painful at first, but this usually decreases over time. ^{6 7 8 9 10}

How is SAINT Stimulation treatment different from other treatments for depression?

SAINT Stimulation is unique because it uses an accelerated form of transcranial magnetic stimulation (TMS), which means it delivers more frequent sessions in a shorter period, potentially leading to faster improvements in depression symptoms compared to standard TMS protocols. ^{2 4 11 12 13}

Research Team

Brandon Bentzley, MD

Principal Investigator

Magnus Medical

Eligibility Criteria

Adults aged 18-75 with Major Depressive Disorder and a current major episode, who haven't responded well to antidepressants. Must not have had certain brain treatments or conditions, be drug-free, agree to use effective contraception, and commit to the study's duration.

Inclusion Criteria

I have been diagnosed with Major Depressive Disorder and am currently experiencing a major depressive episode.

For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation. Must have a negative urine pregnancy test prior to enrollment

My medical records show I have moderate to severe treatment-resistant depression.

Exclusion Criteria

I have a hormone disorder that is untreated or not fully treated.

My low mood is due to a condition other than major depression.

I am not experiencing mania or psychosis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 10 daily sessions of MNS with SAINT stimulation over 5 consecutive days

1 week

5 visits (in-person)

Immediate Post Treatment

Assessment of changes in depressive symptoms and suicidality using MADRS and other scales

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• SAINT Stimulation

Trial Overview The trial is testing SAINT stimulation versus a sham (fake) procedure in hospitalized patients with depression. It's randomized and double-blinded so neither participants nor researchers know who gets real treatment until after the study.

Participant Groups

Group I: Active SAINT Stimulation Active Control 1 Intervention

Active SAINT stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC)

Group II: Sham Stimulation Placebo Group 1 Intervention

Sham (non-active) stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC)

SAINT Stimulation is already approved in United States for the following indications:

Approved in United States as SAINT Neuromodulation System for:

• Major Depressive Disorder (MDD)

Who Is Running the Clinical Trial?

Magnus Medical

Lead Sponsor

Trials

5

Recruited

1,100+

Findings from Research

Transcranial magnetic stimulation (TMS) has been shown to be more effective than placebo for treating depression, but its overall antidepressant effect is considered weak.

The effectiveness of TMS is significantly influenced by the choice of stimulation site, with the left dorsolateral prefrontal area being the most commonly targeted; however, identifying the specific area of metabolic dysfunction using neuroimaging could enhance treatment outcomes, despite making the procedure more complex and costly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[TMS in therapy of depressions - the problem of determining the area to be stimulated, i.e., a few words about the anatomy of depressive disorders]. Zyss, T.[2013]

In a study of 30 patients with major depressive episodes, 73% achieved remission after a second course of Transcranial Magnetic Stimulation (TMS), indicating its effectiveness even after initial treatment failure.

Among patients who did not respond to the first TMS course, 75% achieved remission with the second course, suggesting that TMS can be a valuable option for those who relapse or do not initially respond.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second Courses of Transcranial Magnetic Stimulation (TMS) in Major Depressive Episodes for Initial Responders and Non-Responders. Pridmore, S., Erger, S., May, T.[2022]

An accelerated transcranial magnetic stimulation (TMS) protocol using intermittent theta burst stimulation (iTBS) was safely administered to 19 veterans, with 17 completing the treatment, showing significant reductions in depression symptoms.

The remission and response rates were 47.1% and 64.7%, respectively, indicating that this accelerated protocol is as effective as traditional TMS treatments that last 6 to 9 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An accelerated course of TMS using intermittent theta burst for veterans with major depressive disorder: A case series. Zuschlag, ZD., Bajor, L., Van Trees, K., et al.[2023]

In a study of 120 participants with major depressive disorder, those with more severe depression and anxiety symptoms showed better responses to synchronized transcranial magnetic stimulation (sTMS) treatment after 6 weeks.

Interestingly, individuals who had not previously tried many antidepressants responded better to the sham treatment, suggesting that sTMS may be particularly effective for those with more severe symptoms rather than those who are treatment-naïve.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of response to synchronized transcranial magnetic stimulation for major depressive disorder. Philip, NS., Leuchter, AF., Cook, IA., et al.[2019]

Transcranial magnetic stimulation (TMS) is a non-invasive and painless treatment method that has been used since 1985, initially for diagnostic purposes in neurology and later for therapeutic applications in psychiatry, particularly for depression and schizophrenia.

Recent expert consensus in Europe supports TMS as an effective treatment for depression and schizophrenia, highlighting the need for optimal stimulation parameters to enhance its therapeutic effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Transcranial magnetic stimulation in psychiatric therapy]. Zyss, T., Rachel, W., Datka, W., et al.[2016]

In a randomized controlled trial involving 142 patients, daily left prefrontal rTMS showed a significant 37% reduction in procedural pain over 15 sessions, indicating that patients may adapt to the treatment's discomfort over time.

The decrease in pain was specific to those receiving active rTMS and suggests that the stimulation itself may contribute to pain reduction, rather than just patient accommodation, which could be linked to improved clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The painfulness of active, but not sham, transcranial magnetic stimulation decreases rapidly over time: results from the double-blind phase of the OPT-TMS Trial. Borckardt, JJ., Nahas, ZH., Teal, J., et al.[2021]

Vagus nerve stimulation (VNS) and repetitive transcranial stimulation (rTMS) are both FDA-cleared treatments for resistant depression, but VNS devices are generally considered a contraindication for rTMS due to safety concerns.

Despite this contraindication, clinicians have reported using rTMS in patients with implanted VNS systems, suggesting that with proper precautions and consent procedures, rTMS can be safely administered, as VNS components are typically outside the electromagnetic field of rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe use of repetitive transcranial magnetic stimulation in patients with implanted vagus nerve stimulators. Philip, NS., Carpenter, SL., Carpenter, LL.[2021]

Repetitive transcranial magnetic stimulation (rTMS) is generally safe for older adults with late-life depression, with only 12.4% reporting any adverse events and serious adverse events occurring in just 1.5% of cases, based on a review of 11 studies involving 353 patients.

The most common adverse events were mild, such as headaches (6.9%) and discomfort at the stimulation site (2.7%), although some serious adverse events, including psychiatric hospitalization and increased suicidal ideation, were noted in case reports, highlighting the need for further research to ensure safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. Overvliet, GM., Jansen, RAC., van Balkom, AJLM., et al.[2021]

Transcranial magnetic stimulation (TMS) was effective in treating treatment-resistant depression, with a response rate of 50.6% and a remission rate of 24.7% after 6 weeks of treatment in a cohort of 100 patients.

TMS was well tolerated, showing a low discontinuation rate of 3% and no serious adverse events, indicating its safety as an adjunctive treatment for patients who have not responded to other antidepressant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center. Connolly, KR., Helmer, A., Cristancho, MA., et al.[2022]

Repetitive Transcranial Magnetic Stimulation (rTMS) has been shown to be effective for treating treatment-resistant depression, supported by large-scale randomized controlled trials and real-world studies.

rTMS is generally safe and well-tolerated, with a low risk of seizure occurring in about 1 in 1,000 patients, making it a viable option for individuals who do not respond to standard antidepressant medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[rTMS (Repetitive Transcranial Magnetic Stimulation) for the Treatment of Depression]. Ukai, S.[2019]

A network meta-analysis of 31 randomized sham-controlled trials found that the NeuroStar, MagPro, and Magstim rTMS devices showed no significant differences in efficacy or acceptability for treating therapy-resistant depression.

All three devices had similar response rates, remission rates, and rates of discontinuation, suggesting that patients can choose among these devices without worrying about differences in treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy and Acceptability of 3 Repetitive Transcranial Magnetic Stimulation Devices for Depression: A Meta-Analysis of Randomized, Sham-Controlled Trials. Matsuda, Y., Yamazaki, R., Kishi, T., et al.[2022]

Accelerated low-intensity transcranial magnetic stimulation (LI-TMS) showed significant behavioral improvements in adolescent rats with depression-like symptoms compared to standard once-daily LI-TMS, indicating its potential efficacy for treating depression.

The accelerated LI-TMS protocol did not result in any toxicity or adverse effects, suggesting it is a safe option for further exploration in clinical settings for adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Preclinical Study of Standard Versus Accelerated Transcranial Magnetic Stimulation for Depression in Adolescents. Seewoo, BJ., Hennessy, LA., Jaeschke, LA., et al.[2023]

Transcranial magnetic stimulation (TMS) is a safe and effective treatment for depression, showing therapeutic effects comparable to psychotherapy and antidepressants.

Further research is needed to enhance the efficiency of TMS and to understand its mechanisms of action, as well as to determine the duration of its antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Transcranial magnetic stimulation as a treatment for depression]. Schutter, DJ.[2011]

References

1. Poland pubmed.ncbi.nlm.nih.gov

[TMS in therapy of depressions - the problem of determining the area to be stimulated, i.e., a few words about the anatomy of depressive disorders]. [2013]

2. Malaysia pubmed.ncbi.nlm.nih.gov

Second Courses of Transcranial Magnetic Stimulation (TMS) in Major Depressive Episodes for Initial Responders and Non-Responders. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

An accelerated course of TMS using intermittent theta burst for veterans with major depressive disorder: A case series. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Predictors of response to synchronized transcranial magnetic stimulation for major depressive disorder. [2019]

5. Poland pubmed.ncbi.nlm.nih.gov

[Transcranial magnetic stimulation in psychiatric therapy]. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

The painfulness of active, but not sham, transcranial magnetic stimulation decreases rapidly over time: results from the double-blind phase of the OPT-TMS Trial. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Safe use of repetitive transcranial magnetic stimulation in patients with implanted vagus nerve stimulators. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

[rTMS (Repetitive Transcranial Magnetic Stimulation) for the Treatment of Depression]. [2019]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative Efficacy and Acceptability of 3 Repetitive Transcranial Magnetic Stimulation Devices for Depression: A Meta-Analysis of Randomized, Sham-Controlled Trials. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

A Preclinical Study of Standard Versus Accelerated Transcranial Magnetic Stimulation for Depression in Adolescents. [2023]

13. Netherlands pubmed.ncbi.nlm.nih.gov

[Transcranial magnetic stimulation as a treatment for depression]. [2011]