Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression: OL Cohort (SAINT-TRD)

April 20, 2022 updated by: Nolan R, Stanford University

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

This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for treatment-resistant depression. In this open label study, all participants will receive accelerated theta-burst stimulation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 minutes over the left dorsolateral prefrontal cortex (L-DLPFC) for a 6 week treatment course. This methodology has been successful for many people with treatment-resistant depression. One of the limitations of this approach is the long duration of the treatment course (approximately a 6 weeks per treatment course). Recently, researchers have aggressively pursued modifying the treatment parameters to reduce treatment course time with some preliminary success. This study intends to further modify the parameters to create a more rapid form of the treatment. This study will also look at the change in neuroimaging biomarkers associated with this treatment.

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94305
        • Nolan Williams, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

22 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 an antidepressant therapy but the medication must remain stable throughout study enrollment.
  • Participants may also have a history of intolerance to antidepressant medications. These patients with the intolerance history will not be required to be currently taking an antidepressant medication.
  • 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.
  • 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.
  • History of ECT intolerance is permitted.

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.
  • Total HAMD 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.
  • 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.
  • 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.
  • Positive screening on the urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates.
  • Current (or chronic) use of opiates.
  • History of epilepsy.
  • History of shrapnel or metal in the head or skull.
  • History of cardiovascular disease or cardiac event.
  • History of OCD.
  • History of autism spectrum disorder.
  • History of rTMS exposure

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Accelerated theta burst treatment
All participants will receive theta-burst TMS.
Device: Accelerated theta-burst stimulation treatment

All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).

Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS) Score From Pre-treatment to 1-month
Time Frame: Pre-treatment and 1-month post treatment.
A ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology.
Pre-treatment and 1-month post treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change in the Columbia Suicide Severity Rating Scale (C-SSRS)
Time Frame: Pre-treatment to immediately post-treatment (on day 5) and 4 weeks post-treatment
A suicidal ideation rating scale created by researchers at Columbia University. The score was calculated by summing the answers to 5 questions. Score range - 0 to 5. Higher score indicate higher suicidal ideation.
Pre-treatment to immediately post-treatment (on day 5) and 4 weeks post-treatment
Percent Change in the Hamilton Rating Scale for Depression (HAM-6)
Time Frame: Pre-treatment to immediately post-treatment (on day 5) and 2 weeks,4 weeks and 6 weeks post-treatment
A 6 item questionnaire used to score the severity of depression. Scale range - 0 to 22 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.
Pre-treatment to immediately post-treatment (on day 5) and 2 weeks,4 weeks and 6 weeks post-treatment
Percent Change in the Hamilton Rating Scale for Depression (HAM-17)
Time Frame: Pre-treatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post-treatment
A provider administered questionnaire used to assess remission and recovery from depression. Scale range - 0 to 52 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.
Pre-treatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post-treatment
Change From Baseline Functional Connectivity to 1-month Post-treatment
Time Frame: Pre-treatment, immediately post-treatment (on day 5), 1-month post-treatment
We will assess change in resting state fMRI functional connectivity of the subcallosal cingulate to the default mode network and within the default mode network.
Pre-treatment, immediately post-treatment (on day 5), 1-month post-treatment
Percent Change in the Beck Depression Inventory (BDI-II)
Time Frame: Pretreatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post treatment.
A 21 item Self-report measure of depressive symptoms. Scale range - 0 to 63 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.
Pretreatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post treatment.
Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS)
Time Frame: Pre-treatment to immediately post treatment (on day 5) and 2 weeks, 4 weeks and 8 weeks post-treatment
A ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.
Pre-treatment to immediately post treatment (on day 5) and 2 weeks, 4 weeks and 8 weeks post-treatment
Change From Baseline Functional Connectivity to Immediately Post-treatment
Time Frame: Pre-treatment to immediately post treatment (on day 5).

Within subject changes in resting state functional connectivity of subgenual anterior cingulate cortex (sgACC) to default mode network (DMN). frontal (f)DMN (medial prefrontal cortex), median (m)DMN (posterior cingulate cortex and precuneus), left (l)DMN (left angular gyrus), right (r)DMN (right angular gyrus).

T-statistic (T-score): ratio of departure of estimated value from its hypothesized value to its standard error used in a t-test to determine whether to support or reject the null hypothesis. A T-score of ≥ 2.11 or ≤ -2.11 would be considered a statistically significant change if the accompanying p-value (subject to false discovery rate correction of multiple comparisons) was ≤ 0.05. Positive T-score = increased connectivity, negative T-score = decreased connectivity. No established reference range or clinically meaningful threshold exists for this patient population. Higher connectivity between all DMN nodes to sgACC has been found in depressed vs healthy population.
Pre-treatment to immediately post treatment (on day 5).

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
A Neuropsychological Test Battery Testing Cognitive Abilities
Time Frame: Pre-treatment, immediately post-treatment (on day 5) and 4 weeks post-treatment
The Hopkins Verbal Learning Test - Revised (HVLT-DR). Score range 0 to 72, higher score indicates better verbal learning. The Brief Visuospatial Memory Test - Revised (BVMT-DR). Score range 0 to 84, higher score indicates better visuospatial memory. Digit Span test and various tests from the Delis Kaplan Executive Function System (DKEFS) will be used to assess possible cognitive side-effects. Score range 0-36, higher score indicates better executive functions.
Pre-treatment, immediately post-treatment (on day 5) and 4 weeks post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Collaborators

Schatzberg, Alan, M.D.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 1, 2017

Primary Completion (ACTUAL)

December 1, 2019

Study Completion (ACTUAL)

March 3, 2020

Study Registration Dates

First Submitted

April 23, 2016

First Submitted That Met QC Criteria

August 1, 2017

First Posted (ACTUAL)

August 7, 2017

Study Record Updates

Last Update Posted (ACTUAL)

April 21, 2022

Last Update Submitted That Met QC Criteria

April 20, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 33797

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

clintrials.gov

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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