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

NCT ID: NCT03068715

Last Updated: 2022-05-18

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-20

Study Completion Date

2021-01-09

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Treatment Resistant Depression

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Active TBS-DLPFC

The active group will receive theta-burst TMS stimulation.

Group Type EXPERIMENTAL

Active TBS-DLPFC

Intervention Type DEVICE

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.

Open label TBS-DLPFC

Intervention Type DEVICE

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 TBS-DLPFC

The sham group will receive sham theta-burst TMS stimulation.

Group Type SHAM_COMPARATOR

Sham TBS-DLPFC

Intervention Type DEVICE

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.

Open label TBS-DLPFC

Intervention Type DEVICE

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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DEVICE

Eligibility Criteria

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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.
Minimum Eligible Age

22 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Stanford University

OTHER

Sponsor Role lead

Responsible Party

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Nolan R

Assistaant Professor, Psychiatry & Behavioral Sciences, Stanford University School of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Nolan Williams, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine

Stanford, California, United States

Site Status

Countries

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United States

References

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George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.

Reference Type BACKGROUND
PMID: 20439832 (View on PubMed)

George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008.

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PMID: 8547583 (View on PubMed)

Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. doi: 10.1016/s0140-6736(96)01219-6.

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Chung SW, Hill AT, Rogasch NC, Hoy KE, Fitzgerald PB. Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2016 Apr;63:43-64. doi: 10.1016/j.neubiorev.2016.01.008. Epub 2016 Feb 3.

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Jelic MB, Milanovic SD, Filipovic SR. Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning. Clin Neurophysiol. 2015 May;126(5):1016-23. doi: 10.1016/j.clinph.2014.09.003. Epub 2014 Sep 16.

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Chung SW, Hoy KE, Fitzgerald PB. Theta-burst stimulation: a new form of TMS treatment for depression? Depress Anxiety. 2015 Mar;32(3):182-92. doi: 10.1002/da.22335. Epub 2014 Nov 28.

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PMID: 25450537 (View on PubMed)

Plewnia C, Pasqualetti P, Grosse S, Schlipf S, Wasserka B, Zwissler B, Fallgatter A. Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. J Affect Disord. 2014 Mar;156:219-23. doi: 10.1016/j.jad.2013.12.025. Epub 2013 Dec 28.

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PMID: 24411682 (View on PubMed)

Prasser J, Schecklmann M, Poeppl TB, Frank E, Kreuzer PM, Hajak G, Rupprecht R, Landgrebe M, Langguth B. Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: a randomized placebo controlled trial. World J Biol Psychiatry. 2015 Jan;16(1):57-65. doi: 10.3109/15622975.2014.964768. Epub 2014 Nov 28.

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Daskalakis ZJ. Theta-burst transcranial magnetic stimulation in depression: when less may be more. Brain. 2014 Jul;137(Pt 7):1860-2. doi: 10.1093/brain/awu123. Epub 2014 May 15. No abstract available.

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Thut G, Pascual-Leone A. A review of combined TMS-EEG studies to characterize lasting effects of repetitive TMS and assess their usefulness in cognitive and clinical neuroscience. Brain Topogr. 2010 Jan;22(4):219-32. doi: 10.1007/s10548-009-0115-4. Epub 2009 Oct 28.

Reference Type BACKGROUND
PMID: 19862614 (View on PubMed)

Holtzheimer PE 3rd, McDonald WM, Mufti M, Kelley ME, Quinn S, Corso G, Epstein CM. Accelerated repetitive transcranial magnetic stimulation for treatment-resistant depression. Depress Anxiety. 2010 Oct;27(10):960-3. doi: 10.1002/da.20731.

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Batail JM, Xiao X, Azeez A, Tischler C, Kratter IH, Bishop JH, Saggar M, Williams NR. Network effects of Stanford Neuromodulation Therapy (SNT) in treatment-resistant major depressive disorder: a randomized, controlled trial. Transl Psychiatry. 2023 Jul 3;13(1):240. doi: 10.1038/s41398-023-02537-9.

Reference Type DERIVED
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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.

Reference Type DERIVED
PMID: 34711062 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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Blinded-33797

Identifier Type: -

Identifier Source: org_study_id

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