SAINT for Treatment of Preoperative Depression to Reduce Opioid Use Following Arthroplasty

NCT04195308 | Withdrawn DMC FDA Device

• 1 other identifier: IRB-53022
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Treatment Resistant Depression

Keywords

transcranial magnetic stimulation; theta burst

Outcome Measures

Primary Outcomes (1)

• Change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from pre-treatment to 1-month post-treatment.

  A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders.

  Pretreatment to 1-month posttreatment

Secondary Outcomes (7)

• Percentage change in the Hamilton Rating Scale for Depression (HAMD-17)

  4 weeks posttreatment

• Percentage change in the Columbia Suicide Severity Rating Scale (C-SSRS)

  Pretreatment, immediately posttreatment, 2 weeks posttreatment, 4 weeks posttreatment

• Percentage change in the Hamilton Rating Scale for Depression (HAM-6)

  Follow-up every 2 weeks for 6 months by telephone

• Percentage change in the Hamilton Rating Scale for Depression (HAMD-17)

  Pretreatment, immediately posttreatment, 2 weeks posttreatment

• Change in baseline functional connectivity to immediate post-treatment using functional MRI

  Pretreatment to immediately posttreatment

Study Arms (2)

Active TBS-DLPFC

EXPERIMENTAL

The active group will receive theta-burst TMS stimulation.

Device: Active TBS-DLPFC

Sham TBS-DLPFC

SHAM COMPARATOR

The sham group will receive sham theta-burst TMS stimulation. Participants will have the option of open label TBS-DLPFC treatment following study completion.

Device: Sham TBS-DLPFC; Device: Open label TBS-DLPFC

Interventions

Active TBS-DLPFC 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.

Active TBS-DLPFC

Sham TBS-DLPFC 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.

Sham TBS-DLPFC

Open label TBS-DLPFC DEVICE

Patients will have the option of receiving active, open label aTBS treatment following sham. Stimulation will be delivered to the L-DLPFC using a MagPro stimulator or Nexstim TMS device.

Sham TBS-DLPFC

Eligibility Criteria

• Age: 22 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (16)

• 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.

  PMID: 20439832 BACKGROUND

• 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.

  PMID: 8547583 BACKGROUND

• 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.

  PMID: 8684201 BACKGROUND

• 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.

  PMID: 26850210 BACKGROUND

• 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.

  PMID: 25281475 BACKGROUND

• 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.

  PMID: 25450537 BACKGROUND

• 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.

  PMID: 24411682 BACKGROUND

• 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.

  PMID: 25430687 BACKGROUND

• 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.

  PMID: 24833712 BACKGROUND

• 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.

  PMID: 19862614 BACKGROUND

• 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.

  PMID: 20734360 BACKGROUND

• Fung PK, Robinson PA. Neural field theory of synaptic metaplasticity with applications to theta burst stimulation. J Theor Biol. 2014 Jan 7;340:164-76. doi: 10.1016/j.jtbi.2013.09.021. Epub 2013 Sep 21.

  PMID: 24060620 BACKGROUND

• Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med. 1995 Oct;34(4):537-41. doi: 10.1002/mrm.1910340409.

  PMID: 8524021 BACKGROUND

• Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):253-8. doi: 10.1073/pnas.0135058100. Epub 2002 Dec 27.

  PMID: 12506194 BACKGROUND

• Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9673-8. doi: 10.1073/pnas.0504136102. Epub 2005 Jun 23.

  PMID: 15976020 BACKGROUND

• Greicius MD, Supekar K, Menon V, Dougherty RF. Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex. 2009 Jan;19(1):72-8. doi: 10.1093/cercor/bhn059. Epub 2008 Apr 9.

  PMID: 18403396 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Nolan Williams, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Department of Psychiatry and Behavioral Sciences, Stanford University

Study Record Dates

• First Submitted: October 25, 2019
• First Posted: December 11, 2019
• Study Start: June 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: December 14, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)