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Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD) (aTBS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03068715
Recruitment Status : Completed
First Posted : March 3, 2017
Results First Posted : May 7, 2021
Last Update Posted : May 18, 2022
Sponsor:
Information provided by (Responsible Party):
Nolan R, Stanford University

Brief Summary:
This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for treatment-resistant depression. In a double-blind fashion, half the participants will receive accelerated theta-burst stimulation while half will receive sham treatment.

Condition or disease Intervention/treatment Phase
Treatment Resistant Depression Device: Active TBS-DLPFC Device: Sham TBS-DLPFC Device: Open label TBS-DLPFC Not Applicable

Detailed Description:
Repetitive transcranial magnetic stimulation (rTMS) is an established therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 min over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been effective in real world situations. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session, 5 days per week, for 4-8 weeks). Recently, researchers have pursued modifying the treatment parameters to reduce treatment times with some preliminary successes. This study aims to further modify the parameters to create a more rapid form of the treatment and look at the change in neuroimaging biomarkers.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD)
Actual Study Start Date : March 20, 2017
Actual Primary Completion Date : January 25, 2020
Actual Study Completion Date : January 9, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Active TBS-DLPFC
The active group will receive theta-burst TMS stimulation.
Device: Active TBS-DLPFC

Participants in the active stimulation group will receive intermittent TBS to left DLPFC. The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of RMT and adjusted to the skull to cortical surface distance (see Nahas 2004).

Stimulation will be delivered to the L-DLPFC using a MagPro stimulator.


Device: Open label TBS-DLPFC

All patients will have the option to receive active, open label aTBS treatment after the 1-month mark, following the blinded phase.

Stimulation will be delivered to the L-DLPFC using a MagPro stimulator or Nexstim TMS device.


Sham Comparator: Sham TBS-DLPFC
The sham group will receive sham theta-burst TMS stimulation.
Device: Sham TBS-DLPFC
The parameters in the active arms will be as above with the internal randomization of the device internally switching to sham in a blinded fashion.

Device: Open label TBS-DLPFC

All patients will have the option to receive active, open label aTBS treatment after the 1-month mark, following the blinded phase.

Stimulation will be delivered to the L-DLPFC using a MagPro stimulator or Nexstim TMS device.





Primary Outcome Measures :
  1. Percentage Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Score From Pre-treatment to 1-month Post-treatment. [ Time Frame: Pretreatment (baseline), 1-month post-treatment ]
    A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders.The MADRS has an overall score range from 0-60, with higher scores corresponding to higher levels of depression.


Secondary Outcome Measures :
  1. Percentage Change in the Hamilton Rating Scale for Depression (HAMD-17) [ Time Frame: pre-treatment (baseline) to 1-month post-treatment ]
    A provider administered questionnaire used to assess remission and recovery from depression. The HAMD-17 is a 17-item questionnaire to assess depression severity. Each item is scored from 0-4, with higher scores representing increasing depression severity.

  2. Change in the Columbia Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Pretreatment (baseline) to immediately post-treatment (day 8). ]
    The Columbia-Suicide Severity Rating Scale (C-SSRS) is a questionnaire used for suicide assessment developed by multiple institutions including Columbia University. Participants were asked a series of 6 yes or no questions. Yes answers indicate more suicidal ideation. Here we report a count of participants with an increase, decrease or no change in suicidal ideation.

  3. Change in the Hamilton Rating Scale for Depression (HAM-6) Score [ Time Frame: Baseline (pre-treatment) and at 1-month post-treatment ]

    The Hamilton Depression Rating Scale (HDRS, also known as Ham-D) is the most widely used clinician-administered depression assessment scale.

    The Ham-6 version consists of 6 items assessing for: mood, guilt, general somatic symptoms, work and activities, anxiety and slowness of thought and speech). Each item is scored on a scale of 0 to 4, except for the somatic symptoms item, which is scored 0 to 2. On the HAM-6 there can be a total score of 22. Higher scores represent higher depression severity. Here, we report a count of participants with an overall increase, decrease or no change in total HAM-6 score.

    Participants with an increase in total score (row 3) would signify a worse outcome than participants with a decrease in total score.


  4. Percentage Change in the Hamilton Rating Scale for Depression (HAMD-17) [ Time Frame: Pre-treatment (baseline) to immediately post-treatment (day 8). ]

    The Hamilton Depression Rating Scale (HDRS, also known as Ham-D) is the most widely used clinician-administered depression assessment scale.

    The Ham-17 version consists of 17 items assessing for: mood, guilt, general somatic symptoms, work and activities, anxiety and slowness of thought and speech. Each item is scored on a scale of 0 to 4, except for the somatic, sleep and insight items which are scored 0 to 2. On the HAM-17 there can be a total score of 22. Higher scores represent higher depression severity.


  5. Change From Baseline Functional Connectivity to Immediate Post-treatment [ Time Frame: Pretreatment (baseline) to immediately post-treatment (day 8). ]
    We quantified the functional connectivity change between the subcallosal cingulate to the default mode network and within the default mode network using baseline and immediate post-treatment MRI scans. We report below, changes of functional connectivity (Fisher's Z score of Pearson correlation coefficient for each pair of ROIs) from immediately post-treatment (day 8) to baseline.

  6. Change From Baseline Functional Connectivity to 1-month Post-treatment [ Time Frame: Pretreatment (baseline) to 1-month post-treatment ]
    We will assess functional connectivity as seen on resting state fMRI, between the subcallosal cingulate to the default mode network and within the default mode network. We report below, changes of functional connectivity (Fisher's Z score of Pearson correlation coefficient for each pair of ROIs) from post-treatment(1m) to baseline.

  7. Change in Baseline Heart Rate Variability to 1-month Post-treatment [ Time Frame: Pretreatment to 1-month post-treatment ]
    Heart rate variability measures will be compared pre-treatment and 1-month post-treatment.

  8. Change in Baseline Heart Rate Variability to Immediate Post-treatment [ Time Frame: Pretreatment to immediate post-treatment (day 8). ]
    Heart rate variability measures will be compared pre-treatment and immediately post-treatment.



Information from the National Library of Medicine

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Ages Eligible for Study:   22 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, 22 to 80 years of age.
  • Able to provide informed consent.
  • Diagnosed with Major Depressive Disorder (MDD) and currently experiencing a Major Depressive Episode (MDE).
  • Participants may currently be on a stable and adequate dose of SSRI antidepressant therapy. Participants may choose to not be on antidepressant therapy for the study duration, or to be switched from other classes to a medication from the SSRI class.
  • Participants may also have a history of intolerance to at least 2 antidepressant medications. These patients with the intolerance history will not be required to be currently taking an antidepressant medication.
  • Participants must qualify as "Moderately Treatment Refractory" or "High Treatment Refractory" using the Maudsley staging method.
  • Meet the threshold on the total HAMD17 score of >/=20 at both screening and baseline visits (Day -5/-14 and Day 0).
  • Meet the threshold on the total MADRS score of >/=20 at both screening and baseline visits (Day -5/-14 and Day 0).
  • Meet the threshold on the total BDI-II score of >/=20 at both screening and baseline visits (Day -5/-14 and Day 0).
  • In good general health, as ascertained by medical history.
  • If female, a status of non-childbearing potential or use of an acceptable form of birth control. The form of birth control will be documented at screening and baseline.
  • Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, or trazodone) will be allowed if the therapy has been stable for at least 4 weeks prior to screening and if it is expected to remain stable.

Exclusion Criteria:

  • Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study.
  • Female that is pregnant or breastfeeding.
  • Female with a positive pregnancy test at participation.
  • Total HAMD17 score of < 20 at the screen or baseline visits.
  • Total MADRS score of < 20 at the screen or baseline visits.
  • Total BDI-II score of < 20 at the screen or baseline visits.
  • Current diagnosis of a Substance Use Disorder (Abuse or Dependence, as defined by DSM-IV-TR), with the exception of nicotine dependence, at screening or within six months prior to screening.
  • Current diagnosis of Axis I disorders other than Dysthymic Disorder, Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, or Specific Phobia (unless one of these is comorbid and clinically unstable, and/or the focus of the participant's treatment for the past six months or more).
  • History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes.
  • Any Axis I or Axis II Disorder, which at screening is clinically predominant to their MDD or has been predominant to their MDD at any time within six months prior to screening.
  • Considered at significant risk for suicide during the course of the study.
  • Cognitive impairment (as noted by previous diagnoses-including dementia).
  • Has a clinically significant abnormality on the screening examination that might affect safety, study participation, or confound interpretation of study results.
  • Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation.
  • 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.
  • History of positive screening urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates.
  • Current (or chronic) use of opiates.
  • History of epilepsy.
  • History of rTMS exposure.
  • History of any implanted device or psychosurgery for depression.
  • Any history of ECT (greater than 8 sessions) without meeting responder criteria
  • History of shrapnel or metal in the head or skull.
  • "Low Treatment Refractory" using the Maudsley staging method.
  • History of cardiovascular disease or cardiac event.
  • History of OCD.
  • History of autism spectrum disorder.
  • History of intractable migraine
  • History of independent sleep disorder.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03068715


Locations
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United States, California
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
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Principal Investigator: Nolan Williams, MD Stanford University
  Study Documents (Full-Text)

Documents provided by Nolan R, Stanford University:
Study Protocol  [PDF] September 18, 2018
Statistical Analysis Plan  [PDF] January 25, 2021

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Nolan R, Assistaant Professor, Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT03068715    
Other Study ID Numbers: Blinded-33797
First Posted: March 3, 2017    Key Record Dates
Results First Posted: May 7, 2021
Last Update Posted: May 18, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Nolan R, Stanford University:
transcranial magnetic stimulation
theta burst
Additional relevant MeSH terms:
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Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders