Clinical trial NCT04195308: SAINT for Treatment of Preoperative Depression to Reduce Opioid Use Following Arthroplasty
Official title: Accelerated Intermittent Theta-burst Stimulation for Treatment of Preoperative Depression to Reduce Conversion of Acute to Chronic Opioid Use Following Arthroplasty
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Treatment Resistant Depression
Keywords: transcranial magnetic stimulation
theta burst
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2019-12-11
Enrollment: 0
Sex: ALL
Minimum age (years): 22
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Eligibility criteria: 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.
* 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.
* History of ECT intolerance.
* 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.

Primary outcomes:
measure: Change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from pre-treatment to 1-month post-treatment.
timeFrame: Pretreatment to 1-month posttreatment
Secondary outcomes:
measure: Percentage change in the Hamilton Rating Scale for Depression (HAMD-17)
timeFrame: 4 weeks posttreatment
measure: Percentage change in the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Pretreatment, immediately posttreatment, 2 weeks posttreatment, 4 weeks posttreatment
measure: Percentage change in the Hamilton Rating Scale for Depression (HAM-6)
timeFrame: Follow-up every 2 weeks for 6 months by telephone
measure: Percentage change in the Hamilton Rating Scale for Depression (HAMD-17)
timeFrame: Pretreatment, immediately posttreatment, 2 weeks posttreatment
measure: Change in baseline functional connectivity to immediate post-treatment using functional MRI
timeFrame: Pretreatment to immediately posttreatment
measure: Change in baseline functional connectivity to 1-month post-treatment
timeFrame: Pretreatment to 1-month post-treatment
measure: Change in baseline heart rate variability through immediate post treatment and 1-month post treatment
timeFrame: Pretreatment, immediately posttreatment and 1-month post treatment
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Nolan Williams, MD
role: PRINCIPAL_INVESTIGATOR
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