SAINT for MDD in an Inpatient Setting Follow-on

Major Depressive Disorder Clinical Trial

Official title:

SAINT® Neuromodulation System for the Treatment of Depression in an Inpatient Setting

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06462820
• Other study ID #: CLN-0106
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: June 30, 2024
• Est. completion date: February 28, 2026

Study information

• Verified date: June 2024
• Source: Magnus Medical
• Contact: Katy Stimpson
• Phone: 1-888-537-1530
• Email: katy[@]magnusmed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Randomized, multi-site, sham-controlled, double-blinded study

Description:

This multi-site, double-blind, randomized, sham-controlled mechanistic trial aims to test the effects of Magnus Neuromodulation System (MNS) with Stanford Accelerated Intermittent Neuromodulation Therapy (SAINT) Technology for the treatment of depression and suicidal cognitions in psychiatrically hospitalized patients with Major Depressive Disorder (MDD) and active suicidal ideation (SI). This will be accomplished by applying the MNS with SAINT protocol (10 applications per day to a customized target within the left dorsolateral prefrontal cortex (L-DLPFC) identified with fMRI for five consecutive days) and measuring changes in depressive symptoms and suicidality at baseline and immediate-post visit. Th clinical hypothesis is that participants receiving per-protocol active SAINT stimulation will demonstrate a significant difference in Montgomery-Asberg Depression Rating Scale (MADRS) scores/remission rates at the immediate post treatment visit, compared to those who receive per protocol sham SAINT stimulation. The primary objective of this study is to determine the efficacy of active SAINT vs. sham SAINT in reducing symptoms of depression as measured by the MADRS. The study will enroll approximately 100 participants and employ a two-arm design with 50 subjects per arm. The target population is adults of all genders and ethnicities who are between 18 and 75 years of age with a diagnosis of treatment-resistant MDD experiencing a current Major Depressive Episode, with active suicidal ideation, and who are otherwise in good general health. Participants must be without contraindications to Magnetic Resonance Imaging (MRI) or transcranial magnetic stimulation (TMS) and must be able to attend all study visits. This study will deliver both active and sham SAINT via a MagPro X100 edition (MagVenture, Skovlunde, Denmark) TMS device equipped with a Cool-B65 A/P coil. The stimulation paradigm consists of 10 daily sessions (50 total over 5-days) of MNS with SAINT stimulation (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds), delivered with 50-minute inter-session intervals (10-minute sessions, 50-minutes in between sessions). Stimulation will be delivered at 90% of the resting motor threshold (with depth correction to account for the distance between the scalp and cortex). An operator entered code (derived from the study EDC) will instruct the device to deliver active or sham magnetic stimulation.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: February 28, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Adults of all genders between the ages of 18 and 75 years at the time of screening, who have failed to receive satisfactory improvement from prior antidepressant medication in the current episode

2. Concurrently enrolled in the NIH multi-site trial titled "The Effects of SAINT® Neuromodulation System on Explicit and Implicit Suicidal Cognition"

3. Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires/follow instructions during fMRI assessments and SAINT treatments

4. Stated willingness to comply with all study procedures including availability for the duration of the study and to communicate with study personnel about adverse events and other clinically important information

5. Currently diagnosed with Major Depressive Disorder (MDD) and meets criteria for a current Major Depressive Episode (MDE) according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5)

6. Medical records confirming a history of moderate to severe treatment- resistance as defined by a score of 7-14 on the Maudsley Staging Method153 (MSM)

7. Endorses clinically significant explicit suicidal cognitions (score = 9 on the M-SSI and score = 6 on the BSS self-report)

8. MADRS score of =20 at screening (visit 1)

9. rTMS/iTBS naive

10. Access to ongoing psychiatric care before and after completion of the study

11. Access to clinical rTMS after hospital discharge

12. In good general health, as evidenced by medical history

13. 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

Exclusion Criteria:

1. Pregnancy as confirmed by a positive urine pregnancy test

2. The presence or diagnosis of a prominent anxiety disorder, personality disorder, or dysthymia which in the Investigator's opinion is predominant to MDD

3. Depressed mood/dysphoria as a result of an illness other than MDD (e.g. gender dysphoria)

4. Current severe insomnia (must sleep a minimum of 5 hours each night before stimulation)

5. Current mania or psychosis

6. A history of Bipolar Affective Disorder or Primary Psychotic Disorder

7. Autism Spectrum disorder or Intellectual Disability

8. A diagnosis of obsessive-compulsive disorder (OCD)

9. Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal

10. Urine screening test positive for illicit substances

11. Any history of ECT (greater than 8 sessions) without meeting responder criteria

12. Recent (during the current depressive episode) or concurrent use of a rapid acting antidepressant agent (i.e., ketamine or a course of ECT)

13. History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, unexpected seizure/epilepsy disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma

14. Untreated or insufficiently treated endocrine disorder

15. Contraindications to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion)

16. Contraindications to MRI (ferromagnetic metal in their body)

17. Any current or past history of any physical condition which, in the investigator's opinion, might put the subject at risk or interfere with study results interpretation

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

19. Depth-adjusted SAINT® treatment dose > 65% maximum stimulator output (MSO)

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

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder
• Major Depressive Episode
• Suicidal Ideation

Intervention

Device:
• Active SAINT Stimulation
Participants who are randomly assigned to this group will receive active SAINT targeted to the left DLPFC. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth). Stimulation will be delivered using the Magventure Magpro X100 TMS system with the Cool-B65 A/P coil.
• Sham SAINT Stimulation
Participants who are randomly assigned to this group will receive sham stimulation targeted to the left DLPFC. Sham stimulation will be delivered using the Magventure Magpro X100 TMS system with the Cool-B65 A/P coil.

Locations

Country	Name	City	State
United States	University of Texas, Ausin - Department of Psychiatry and Behavioral Sciences	Austin	Texas
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Iowa	Iowa City	Iowa
United States	Weill Cornell Medicine	Manhattan	New York

Sponsors (1)

Lead Sponsor	Collaborator
Magnus Medical

Country where clinical trial is conducted

United States, 

References & Publications (3)

Cole EJ, Phillips AL, Bentzley BS, Stimpson KH, Nejad R, Barmak F, Veerapal C, Khan N, Cherian K, Felber E, Brown R, Choi E, King S, Pankow H, Bishop JH, Azeez A, Coetzee J, Rapier R, Odenwald N, Carreon D, Hawkins J, Chang M, Keller J, Raj K, DeBattista C, Jo B, Espil FM, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial. Am J Psychiatry. 2022 Feb;179(2):132-141. doi: 10.1176/appi.ajp.2021.20101429. Epub 2021 Oct 29. — View Citation

Cole EJ, Stimpson KH, Bentzley BS, Gulser M, Cherian K, Tischler C, Nejad R, Pankow H, Choi E, Aaron H, Espil FM, Pannu J, Xiao X, Duvio D, Solvason HB, Hawkins J, Guerra A, Jo B, Raj KS, Phillips AL, Barmak F, Bishop JH, Coetzee JP, DeBattista C, Keller J, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. Am J Psychiatry. 2020 Aug 1;177(8):716-726. doi: 10.1176/appi.ajp.2019.19070720. Epub 2020 Apr 7. — View Citation

Williams NR, Sudheimer KD, Bentzley BS, Pannu J, Stimpson KH, Duvio D, Cherian K, Hawkins J, Scherrer KH, Vyssoki B, DeSouza D, Raj KS, Keller J, Schatzberg AF. High-dose spaced theta-burst TMS as a rapid-acting antidepressant in highly refractory depression. Brain. 2018 Mar 1;141(3):e18. doi: 10.1093/brain/awx379. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Montgomery-Asberg Depression Rating Scale (MADRS) Remission Rates	Ten item diagnostic questionnaire which psychiatrists use to measure the severity of depressive symptoms in patients with mood disorders.; We will assess the difference in MADRS scores/remission rates between the per-protocol active SAINT group compared to those who received per-protocol sham treatment at the immediate post treatment visit.	Screening/Baseline, Immediate Post Visit
Secondary	Modified Scale for Suicidal Ideation (M-SSI)	A revised version of the Scale for Suicidal Ideation (SSI; Beck et al., 1979). The MSSI is an 18 item scale that contains 13 items from the SSI and 5 additional items.; We will assess the mean change in the M-SSI from baseline to immediate post treatment visits between the per-protocol active SAINT group compared to those who received per-protocol sham treatment.	Screening/Baseline, Immediate Post Visit
Secondary	Columbia Suicide Severity Rating Scale (C-SSRS)	We will use both the Lifetime and the Since Last Visit versions of the C-SSRS to assess suicidality from baseline to immediate post treatment between the per-protocol active SAINT group compared to those who received per-protocol sham treatment.	Screening/Baseline, Immediate Post Visit
Secondary	Montgomery-Asberg Depression Rating Scale (MADRS) Response Rates	We will assess the difference in MADRS response rates (reduction >50% of MADRS baseline score) between the per-protocol active SAINT group compared to those who received per-protocol sham treatment at the immediate post treatment visit.	Screening/Baseline, Immediate Post Visit