Accelerated Brain Stimulation for Depression

(SAINT®SC Trial)

Recruiting at 4 trial locations

Overseen By Mark George, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Magnus Medical

Must not be taking: Ketamine, ECT

Disqualifiers: Anxiety, Bipolar, Substance use, 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 magnetic pulse therapy on adults with severe depression and suicidal thoughts. The therapy targets a specific brain area to change brain communication, aiming to reduce suicidal thoughts and improve mood.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the treatment Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) for depression?

Research shows that Stanford neuromodulation therapy (SNT), previously known as SAINT, achieved a remission rate of about 90% in patients with treatment-resistant depression after just 5 days of treatment in a double-blind trial. ^{1 2 3 4 5}

Is accelerated brain stimulation for depression safe for humans?

Repetitive transcranial magnetic stimulation (rTMS), a similar technique, is generally considered safe for treating depression, even in patients with implanted devices, though special precautions may be needed. Safety data for other forms of magnetic stimulation, like Low-Field Magnetic Stimulation (LFMS), also suggest it is non-invasive and safe, with no major safety concerns reported in preliminary studies. ^{3 5 6 7 8}

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

The SAINT treatment is unique because it uses an accelerated protocol of intermittent theta-burst stimulation (iTBS), which significantly reduces the treatment duration to just 5 days and achieves a high remission rate of about 90% for treatment-resistant depression, compared to the traditional 6-week course of iTBS. ^{3 4 5 9 10}

Research Team

Brandon Bentzley, MD

Principal Investigator

Magnus Medical

Eligibility Criteria

Adults aged 18-75 with major depressive disorder or bipolar II experiencing a current major depressive episode, who have not responded well to previous treatments. Participants must be in good health, avoid pregnancy, caffeine, alcohol and tobacco during the trial. They should also be able to understand English and provide consent.

Inclusion Criteria

Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and aiTBS treatments

I am between 18 and 75 years old.

I have never had rTMS or iTBS treatments.

Exclusion Criteria

Treatment with another investigational drug or other intervention within the study period

My treatment's intensity is more than 65% of the maximum level.

Any other condition deemed by the PI to interfere with the study or increase risk to the participant

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SAINT neuromodulation therapy targeting the left dorsolateral prefrontal cortex for five consecutive days

1 week

5 visits (in-person)

Follow-up

Participants are monitored for changes in neural connectivity and suicidal cognition post-treatment

1 week

2 visits (in-person)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Sham Stimulation
• Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT)

Trial Overview The study is testing an accelerated form of brain stimulation therapy called SAINT against sham (fake) stimulation for its effects on suicidal thoughts in patients with severe depression. The goal is to see if this intensive treatment can change how the brain processes these thoughts.

Participant Groups

Group I: 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)

Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) is already approved in United States for the following indications:

Approved in United States as SAINT Neuromodulation System for:

• Major Depressive Disorder (MDD) in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication

Who Is Running the Clinical Trial?

Magnus Medical

Lead Sponsor

Trials

5

Recruited

1,100+

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

A review of neuromodulation therapies (NTs) for treatment-resistant depression (TRD) found that 30%-93% of patients showed substantial improvement, indicating these therapies can be effective for many individuals who do not respond to traditional treatments.

NTs generally have a good safety profile with benign side effects, although some methods like modified electroconvulsive therapy may cause temporary neurocognitive issues, highlighting the need for further research to optimize these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation therapies and treatment-resistant depression. Al-Harbi, KS., Qureshi, NA.[2021]

Depression is a major public health issue, often leading to disability, and many patients do not respond to conventional antidepressants, particularly in cases of treatment-resistant depression.

Non-invasive neuromodulation techniques, which use electric currents or magnetic fields, offer a promising new treatment option for patients who have not found relief with traditional antidepressant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain stimulation for treatment-resistant depression. Rodrigues, A., Martins, L., Villela, NR., 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]

Stanford neuromodulation therapy (SNT), an accelerated protocol of intermittent theta-burst stimulation (iTBS), showed a significant reduction in depression symptoms, with a 52.5% decrease in Montgomery-Åsberg Depression Rating Scale (MADRS) scores after 4 weeks in the active treatment group compared to only 11.1% in the sham group.

This study involved 32 participants with treatment-resistant depression, and the results suggest that SNT is more effective than sham stimulation, indicating its potential as a promising treatment option, although further research is needed to assess its long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial. Cole, EJ., Phillips, AL., Bentzley, BS., et al.[2022]

In a study involving 84 subjects with treatment-resistant depression, Low-Field Magnetic Stimulation (LFMS) did not show a significant improvement in mood compared to sham treatment after two and four days of therapy.

While LFMS was generally well tolerated, the results suggest that more intensive or longer-duration treatments may be necessary to observe therapeutic effects, as no substantial differences were found in primary and secondary outcome measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, proof-of-concept (POC) trial of Low-Field Magnetic Stimulation (LFMS) augmentation of antidepressant therapy in treatment-resistant depression (TRD). Fava, M., Freeman, MP., Flynn, M., et al.[2022]

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]

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]

In a study of 46 patients with drug-resistant depression, using a neuronavigated MR-less rTMS system allowed for targeted stimulation of different brain regions, leading to varying clinical outcomes and physiological effects.

Group 3, which received stimulation at a specific target, showed the greatest reduction in depression symptoms (66.94% decrease in HAM-D scores), suggesting that precise targeting in rTMS can enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of MR‑less MNI based neuronavigation for 10 Hz rTMS depression therapy: electrophysiological and clinical implications. Valiulis, V., Gerulskis, G., Dapšys, K., et al.[2019]

Accelerated transcranial magnetic stimulation (aTMS) shows promising results as a treatment for treatment-resistant depression (TRD), potentially offering similar safety and efficacy to conventional repetitive transcranial magnetic stimulation (rTMS) but with a faster response rate when using more intensive protocols.

Current studies suggest that aTMS may require fewer sessions and a shorter duration for effective treatment, but more rigorous sham-controlled trials with larger participant groups are necessary to fully establish its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated transcranial magnetic stimulation for the treatment of Patients with depression: A review. Rachid, F.[2019]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Neuromodulation therapies and treatment-resistant depression. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Brain stimulation for treatment-resistant depression. [2023]

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

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

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

Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial. [2022]

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

Double-blind, proof-of-concept (POC) trial of Low-Field Magnetic Stimulation (LFMS) augmentation of antidepressant therapy in treatment-resistant depression (TRD). [2022]

6. 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]

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

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

8. Poland pubmed.ncbi.nlm.nih.gov

The use of MR‑less MNI based neuronavigation for 10 Hz rTMS depression therapy: electrophysiological and clinical implications. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Accelerated transcranial magnetic stimulation for the treatment of Patients with depression: A review. [2019]

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

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