Accelerated Brain Stimulation for Depression

(SAINT®SC Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) to assist people hospitalized for major depression with suicidal thoughts. The study tests whether this brain stimulation method can alter brain connections to reduce these dangerous thoughts. Participants will receive either the actual treatment or a non-active version (Sham Stimulation) to compare effects. The trial seeks individuals diagnosed with major depression who experience significant suicidal thoughts and have not responded well to standard treatments. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking advancements in depression treatment.

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 prior data suggests that the Magnus Neuromodulation System with SAINT Technology is safe for treating depression?

Studies have shown that Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) is generally safe and easy for people to handle. This therapy uses high-dose repetitive transcranial magnetic stimulation (rTMS), guided by brain scans. Research has shown that people who received this treatment for depression found it tolerable.

While more research is needed to confirm its safety in various situations, the current results are encouraging. This treatment builds on rTMS, a technology already used for depression, which supports its reliability. Overall, current evidence suggests that SAINT is a safe option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for depression?

Unlike the standard treatments for depression, such as medication and traditional therapy, Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) offers a novel approach by focusing on brain stimulation. SAINT is unique because it targets the left dorsolateral prefrontal cortex (DLPFC) with accelerated neuromodulation, potentially providing faster relief from depression symptoms. Researchers are excited about this treatment because it could offer significant improvements in a shorter time frame compared to existing options, which often take weeks to show results. Additionally, the use of precise brain stimulation may reduce the side effects commonly associated with antidepressant medications.

What evidence suggests that the Magnus Neuromodulation System with SAINT Technology is effective for Major Depressive Disorder with suicidal ideation?

Research has shown that Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), a treatment under study in this trial, can help people with depression unresponsive to other treatments. SAINT uses magnetic pulses to target specific brain areas involved in mood control. Studies have found this method safe and capable of quickly reducing depression symptoms. Additionally, SAINT has improved connectivity between different brain parts, easing depression. This therapy holds promise, especially for those who haven't benefited from other treatments. Participants in this trial may receive either active SAINT stimulation or a sham (non-active) stimulation for comparison. ^{1 2 3 5 6}

Who Is on the Research Team?

Brandon Bentzley, MD

Principal Investigator

Magnus Medical

Are You a Good Fit for This Trial?

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

I have never had rTMS or iTBS treatments.

I can get rTMS treatment after leaving the hospital.

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

Exclusion Criteria

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/32252538/

Stanford Accelerated Intelligent Neuromodulation Therapy for ...

SAINT, an accelerated, high-dose, iTBS protocol with fcMRI-guided targeting, was well tolerated and safe. Double-blinded sham-controlled trials are needed.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03068715

Study Details | NCT03068715 | Stanford Accelerated ...

This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for treatment-resistant depression.

3.

psychiatryonline.org

psychiatryonline.org/doi/10.1176/appi.ajp.2019.19070720

Stanford Accelerated Intelligent Neuromodulation Therapy ...

The aim of this study was to examine the safety, feasibility, and preliminary efficacy of an accelerated, high-dose, fcMRI-guided iTBS treatment ...

4.

brainstimjrnl.com

brainstimjrnl.com/article/S1935-861X(24)00241-9/fulltext

Magnus Neuromodulation System with Stanford ...

SAINT, an fMRI-guided, accelerated repetitive transcranial magnetic stimulation treatment protocol, has been demonstrated to be a safe, highly effective, and ...

5.

med.stanford.edu

med.stanford.edu/content/dam/sm/mooddisorders/documents/2022/Williams%20N%20SAINT.pdf

Stanford Accelerated Intelligent Neuromodulation Therapy

A recently completed non-inferiority trial demonstrated that 600 pulses of iTBS (3 min protocol) is non-inferior to 3,0000 pulses of 10hz. rTMS (37 min protocol) ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03240692

Study Details | NCT03240692 | Stanford Accelerated ...

Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy for treatment-resistant depression.