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Accelerated Theta Burst in Treatment-Resistant Depression (aTBS)

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ClinicalTrials.gov Identifier: NCT03068715
Recruitment Status : Recruiting
First Posted : March 3, 2017
Last Update Posted : September 5, 2018
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 technology as 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 very successful in real world situations. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session). Recently, researchers have aggressively pursued modifying the treatment parameters to reduce treatment times with some preliminary success. This study intents to further modify the parameters to create a more rapid form of the treatment and look at the change in neuroimaging biomarkers.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Accelerated Theta Burst in Treatment-Resistant Depression: A Dose Finding and Biomarker Study
Actual Study Start Date : March 20, 2017
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 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 80% 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.


Sham Comparator: Sham TBS-DLPFC
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
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
Patients will have the option of receiving active, open label aTBS treatment following sham.




Primary Outcome Measures :
  1. Percentage change in Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: Pretreatment, immediately posttreatment, 2 weeks posttreatment, 4 weeks posttreatment ]
    A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders.


Secondary Outcome Measures :
  1. Hamilton Rating Scale for Depression (HAMD-17) [ Time Frame: 4 weeks posttreatment ]
    A provider administered questionnaire used to assess remission and recovery from depression.

  2. Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Pretreatment, immediately posttreatment, 2 weeks posttreatment, 4 weeks posttreatment ]
    A suicidal ideation rating scale created by researchers at Columbia University.

  3. Hamilton Rating Scale for Depression (HAM-6) [ Time Frame: Follow-up every 2 weeks for 6 months by telephone ]
    A 6 item questionnaire used to score the severity of depression.

  4. Hamilton Rating Scale for Depression (HAMD-17) [ Time Frame: Pretreatment, immediately posttreatment, 2 weeks posttreatment ]
    A provider administered questionnaire used to assess remission and recovery from depression.

  5. Change from baseline functional connectivity immediately posttreatment [ Time Frame: Pretreatment, immediately posttreatment ]
    Functional connectivity of subcallosal cingulate to the default mode network and within the default mode network.

  6. Change from baseline functional connectivity at 4 weeks posttreatment [ Time Frame: Pretreatment, 4 weeks posttreatment ]
    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.

  7. Change in heart rate variability [ Time Frame: Pretreatment, during treatment, immediately posttreatment, weekly posttreatment ]
    Heart rate variability measures will be compared pre-treatment and at several time points post-treatment.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, 18 to 70 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 HAMD21 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 HAMD 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.
  • Current (or chronic) use of opiates.
  • History of epilepsy.
  • History of rTMS failure with FDA approved rTMS parameters.
  • History of any implanted device or psychosurgery for depression.
  • History of receiving ECT.
  • 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 headache.
  • 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


Contacts
Contact: Claudia K Tischler, BA 6504988535 ctischler@stanford.edu

Locations
United States, California
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine Recruiting
Stanford, California, United States, 94305
Contact: Claudia K Tischler, BA    650-498-8535    ctischler@stanford.edu   
Principal Investigator: Nolan Williams, MD         
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Nolan Williams, MD Stanford University

Publications:

Responsible Party: Nolan R, Instructor of Psychiatry & Behavioral Sciences, Director of the Brain Stimulation Laboratory at Stanford University School of Medicine, Stanford University, Stanford University
ClinicalTrials.gov Identifier: NCT03068715     History of Changes
Other Study ID Numbers: IRB-33797
First Posted: March 3, 2017    Key Record Dates
Last Update Posted: September 5, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
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:
Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders