Clinical trial NCT03749967: rTMS for Emotional Difficulties in Verterans
Official title: Developing a Novel rTMS Intervention for Transdiagnostic Psychosocial Rehabilitation: A Dose Finding Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Mental Health
Depression
rTMS
Anxiety
PTSD
Psychosocial Impairment
Keywords: Depression
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2018-11-21
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Veterans will be randomized to 10 different doses of accelerated intermittent theta burst rTMS for remediation of transdiagnostic psychosocial impairment. The goal is to determine the optimal dose in terms of efficacy while minimizing burden and side effects.
Primary purpose: TREATMENT

Brief summary: Mental illness rarely occurs as a single, easily categorized condition. Instead, multiple disorders often co-occur. This complicates the treatment plan for many Veterans, especially those suffering the most severe dysfunction. This also means that clinical research aimed at one specific disorder may not be optimized to treat the realworld presentation of neuropsychiatric illness. The investigators propose in this study to develop a novel, non-invasive brain stimulation treatment that would promote rehabilitation for Veterans suffering a wide range of emotional difficulties. More specifically, the investigators propose to up-regulate the brain circuitry that supports flexible problem solving and contending with daily demands. Rather than focusing on reducing the symptoms of a specific disorder to reduce the intrusion into daily life, the investigators propose to augment those brain circuits that promote adaptive cognition and thus quality of life.

Detailed description: The investigators propose that because rTMS to dlPFC is targeting cognitive neurocircuitry integral to adaptive cognitive functioning, promoting neuroplasticity in this network with rTMS could be more precisely optimized to improve quality of life across psychosocial domains and across neuropsychiatric presentations. The investigators postulate that through up-regulating cognitive control circuitry with rTMS that an individual would have 1) enhanced capacity for successfully contending with the shifting contingencies of daily life and 2) improved ability to regulate intrusive affect and impulses. As a function of these processes an individual is expected to experience reduced psychosocial impairment. Thus, the investigators propose that rather than targeting specific symptom reductions in specific disorders, rTMS could be dosed for efficacy in enhancing psychosocial functioning. Such an approach has the potential to enhance rehabilitation for far more Veterans suffering a range of neuropsychiatric conditions.

Aim 1. Establish the dose-response curve for improved psychosocial functioning secondary to accelerated rTMS in a transdiagnostic anxious and depressed sample of Veterans.

Aim 2. Establish the safety, feasibility, and acceptability of an accelerated delivery schedule of therapeutic rTMS for improved psychosocial functioning in a transdiagnostic anxious and depressed sample of Veterans.

Exploratory Aim 3. Establish whether neurocognitive function demonstrates a dose-response function to accelerated rTMS similar to psychosocial functioning in a transdiagnostic anxious and depressed sample.

Note: COVID-19 pandemic put a pause on enrollment.

Eligibility criteria: Inclusion Criteria:

* A negative urine pregnancy test, if female subject of childbearing potential.
* Able to speak English and complete study forms, adhere to treatment regimens, and be willing to return for regular visits.
* After full explanation of the study, willingness of participant is demonstrated by signing the informed consent form.

Exclusion Criteria:

* Clinically unstable medical disease:

  * cardiovascular
  * renal
  * gastrointestinal
  * pulmonary
  * metabolic
  * endocrine
  * other
  * CNS disease deemed progressive
  * Moderate or severe traumatic brain injury (TBI) - (using VA/DoD Clinical Practice Guidelines)
* Pregnant females or those currently breast-feeding.
* Current or history of schizophrenia or other psychotic disorder, except psychosis not otherwise specified (NOS) when the presence of sensory hallucinations is clearly related to the subject's trauma, Bipolar Type I disorder, or dementia

  * vascular
  * Alzheimer's disease
  * other types)
* Repeated abuse or dependence upon drugs (excluding nicotine and caffeine) within 6 days of study entry, with the exception of alcohol use disorder, which, at the discretion of the study team, may be permitted.

  * See further explanation under protection from risk.
* Active participation or plan for enrollment in another evidence-based psychotherapeutic clinical trial

  * Participation in other psychotherapeutic modalities must have been stable for 3 months prior to enrollment and must remain stable throughout participation.
* Currently taking medications that have short half-lives, lower the seizure threshold, and do not have evidence of antidepressant efficacy. These include:

  * high dose theophylline or stimulants such as methylphenidate
  * patients taking bupropion must be on a stable dose and take less than or equal to 300 mg/day. Stable means the same dose for 5 half-lives.
* An implanted device in subject's head (shunt, cochlear implant) and/or metal in subject's head (other than dental implant).

History of seizures or a seizure disorder.

Primary outcomes:
measure: Inventory of Psychosocial Functioning (IPF)
timeFrame: 4 weeks post-treatment
measure: World Health Organization Quality of Life - Brief Form (WHOQOL-BF)
timeFrame: 4 weeks post-treatment
measure: Illness Intrusiveness Rating Scale (IIRS)
timeFrame: 4 weeks post-treatment
Secondary outcomes:
measure: Neurocognitive performance
timeFrame: 4 weeks post-treatment
measure: Inventory of Depression and Anxious Symptoms (IDAS-II)
timeFrame: 4 weeks post-treatment
measure: Hamilton Scale for Depression (HAM-D)
timeFrame: 4 weeks post-treatment
measure: Mood and Anxiety Symptom Questionnaire (MASQ)
timeFrame: 4 weeks post-treatment
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Ralph H. Johnson VA Medical Center, Charleston, SC
state: South Carolina
Study officials:
affiliation: Ralph H. Johnson VA Medical Center, Charleston, SC
name: Lisa M. McTeague, PhD
role: PRINCIPAL_INVESTIGATOR
References: