Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression: OL Cohort

Treatment Resistant Depression Clinical Trial

— SAINT-TRD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03240692
• Other study ID #: 33797
• Status: Completed
• Phase: N/A
• Start date: May 1, 2017
• Est. completion date: March 3, 2020

Study information

• Verified date: April 2022
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: March 3, 2020
• Est. primary completion date: December 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant
• Treatment Resistant Depression

Intervention

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.

Locations

Country	Name	City	State
United States	Nolan Williams, MD	Palo Alto	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	Schatzberg, Alan, M.D.

Country where clinical trial is conducted

United States, 

References & Publications (16)

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. Epub 2005 Jun 23. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2002 Dec 27. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Pascual-Leone A, Rubio B, Pallardó F, Catalá MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	A Neuropsychological Test Battery Testing Cognitive Abilities	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
Primary	Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS) Score From Pre-treatment to 1-month	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	Percent Change in the Columbia Suicide Severity Rating Scale (C-SSRS)	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
Secondary	Percent Change in the Hamilton Rating Scale for Depression (HAM-6)	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
Secondary	Percent Change in the Hamilton Rating Scale for Depression (HAM-17)	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
Secondary	Change From Baseline Functional Connectivity to 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
Secondary	Percent Change in the Beck Depression Inventory (BDI-II)	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.
Secondary	Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS)	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
Secondary	Change From Baseline Functional Connectivity to Immediately Post-treatment	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).