Clinical trial NCT05537285: Individualized Neuromodulation for Anhedonic Depression
Official title: Individualized Neuromodulation for Anhedonic Depression
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: MDD
Anhedonia
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Cornell University
name: Stanford University
name: Wellcome Leap Organization
First posted: 2022-09-13
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients enrolled in the study will be evenly randomized into one of three treatment groups: Individualized Accelerated Intermittent Theta-Burst Stimulation (Ind-aiTBS), Standard aiTBS (Std-aiTBS). Treatments will last 1 week in all three arms.
Primary purpose: TREATMENT

Brief summary: This program of research constitutes a three-arm, randomized, placebo-controlled trial testing noninvasive brain stimulation for the treatment of anhedonic depression. This trial is part of a larger, three-site study that will be conducted at UCSD, Stanford University, and Cornell University, with the overarching goals to compare competing interventions tested at each site and to combine data that will allow for the creation of an end-to-end model of anhedonic depression. By doing this, the investigators hope to gain insight and lead to the development of brain-behavior biomarkers to identify who is best suited for the different treatment options tested at each site. An additional exploratory objective is phenotyping anhedonic depression from the acquired measures.

Anhedonic patients recruited at UCSD will be randomized to one of three treatment arms to receive different forms of accelerated intermittent theta burst stimulation (aiTBS),a novel form of repetitive transcranial magnetic stimulation (rTMS) that is an FDA approved treatment for depression. These arms include: individualized accelerated iTBS (Ind-aiTBS),based on both the frequency of brain responses and electric-field (e-field) modeling of brain bioconductivity; standard accelerated iTBS (Std-aiTBS); and accelerated sham iTBS(sham). Treatment will be delivered on an accelerated schedule, over one week. Additional study sessions will occur both before and after treatment to assess for clinical, neurophysiological, and cognitive measures that will allow for both individualization of treatment and detailed assessment of the effects of the different treatment arms.


Eligibility criteria: Inclusion Criteria:

* Male or Female, between the ages of 18 and 80 at the time of screening.
* Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and aiTBS interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
* Currently diagnosed with Major Depressive Disorder (MDD) or Bipolar Disorder type II and meets criteria for a Major Depressive Episode, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
* Medical records confirming a history of moderate to severe treatment-resistance as defined an Antidepressant Treatment History Form (ATHF) score for that antidepressant trial of \> 3 in the current episode OR have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF score of 1 or 2 on those 2 separate antidepressants) OR have a combination of one failed trial and one not tolerated trial, per the definitions above.
* MADRS score of ≥20 at screening (Visit 1).
* Access to ongoing psychiatric care before and after completion of the study.
* Access to open label neuromodulation treatment after study completion.
* Must be on a stable antidepressant therapeutic regimen for 6 weeks prior to study enrollment and agree to continue this regimen throughout the study period.
* In good general health, as evidenced by medical history.
* For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.
* Agreement to adhere to Lifestyle Considerations throughout study duration.

Exclusion Criteria:

* Pregnancy
* History of or current psychotic disorder or depression with psychotic features
* Severe borderline personality disorder.
* Diagnosis of Intellectual Disability or Autism Spectrum Disorder
* Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal
* Urine screening test positive for illicit substances
* Clinically significant suicidal ideation with plan
* Any history of ECT (greater than 8 sessions) without a clinical meaningful response.
* Recent (during the current depressive episode) or concurrent use of rapid acting antidepressant agent (i.e., ketamine or a course of ECT) in the last 30 days
* History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma
* Untreated or insufficiently treated endocrine disorder.
* Contraindication to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion)
* Contraindication to MRI (ferromagnetic metal in their body)
* Treatment with an investigational drug or other intervention within the study period
* Unstable symptoms between screening and baseline as defined by a ≥ 30% change in MADRS score.
* Require a benzodiazepine with a dose \> lorazepam 2 mg/day or equivalent or any anticonvulsant.

Primary outcomes:
measure: Change in MADRS Scores
timeFrame: 8 weeks
measure: Change in DARS Scores
timeFrame: 8 weeks
Secondary outcomes:
measure: Assessment of Neuroplasticity
timeFrame: 8 weeks
Other outcomes:
measure: Predictive TMS-EEG Biomarker
timeFrame: 8 weeks
measure: Predictive fMRI Biomarker
timeFrame: 8 weeks
measure: Cross-Sectional TMS-EEG Biomarker
timeFrame: 8 weeks
measure: Cross-Sectional fMRI Biomarker
timeFrame: 8 weeks
Locations:
city: San Diego
country: United States
facility: UCSD Interventional Psychiatry
state: California
Study officials:
References: