MedPath

rTMS for Emotional Difficulties in Verterans

Phase 1
Completed
Conditions
Depression
rTMS
Anxiety
Mental Health
PTSD
Psychosocial Impairment
Interventions
Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
Registration Number
NCT03749967
Lead Sponsor
VA Office of Research and Development
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
21
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Dose 2Repetitive Transcranial Magnetic Stimulation (rTMS)All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 2 is ten sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 8Repetitive Transcranial Magnetic Stimulation (rTMS)All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 1 is forty sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 3Repetitive Transcranial Magnetic Stimulation (rTMS)All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 1 is fifteen sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 1Repetitive Transcranial Magnetic Stimulation (rTMS)All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 1 is five sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 4Repetitive Transcranial Magnetic Stimulation (rTMS)All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 1 is twenty sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 5Repetitive Transcranial Magnetic Stimulation (rTMS)All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 1 is twenty-five sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 6Repetitive Transcranial Magnetic Stimulation (rTMS)All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 1 is thirty sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 7Repetitive Transcranial Magnetic Stimulation (rTMS)All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 1 is thirty-five sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 9Repetitive Transcranial Magnetic Stimulation (rTMS)All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 1 is forty-five sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 10Repetitive Transcranial Magnetic Stimulation (rTMS)All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 1 is fifty sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Primary Outcome Measures
NameTimeMethod
World Health Organization Quality of Life - Brief Form (WHOQOL-BF)4 weeks post-treatment

The WHOQOL-BREF is a 26-item self-assessment form. Questions are rated on a 5 point scale (from 1-5) Likert scale. Reflects four domains: physical, psychological, social and environment.

Inventory of Psychosocial Functioning (IPF)4 weeks post-treatment

The IPF is an 80-item self-report measure used to assess functional impairment across multiple psychosocial domains of functioning. It was iteratively developed in 697 male and female Veteran stakeholders to identify relevant domains of functional impairment common in PTSD and related psychiatric dysfunction. Total score range=0-480. Increased scores pre- to 4 weeks post-treatment would indicate improved function.

Illness Intrusiveness Rating Scale (IIRS)4 weeks post-treatment

The IIRS is a self-report measure of the extent of psychosocial impairment secondary to illness. Total score range=13-91. Decreased scores pre- to 4 weeks post-treatment would indicate improved function.

Secondary Outcome Measures
NameTimeMethod
Inventory of Depression and Anxious Symptoms (IDAS-II)4 weeks post-treatment

Questions are rated on a scale from 1-5 and covers a wide array of psychological measures

Hamilton Scale for Depression (HAM-D)4 weeks post-treatment

Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. 10 - 13 mild; 14-17 mild to moderate; \>17 moderate to severe.

Neurocognitive performance4 weeks post-treatment

Participants would complete a computerized battery, which includes well-validated computer-adaptations of neuropsychological tests. Tasks assess the following domains: information-processing speed, executive function, sustained attention/vigilance, verbal memory, working-memory capacity, inhibition/impulsivity, and sensorimotor function. Improved performance pre- to 4 weeks post-treatment would indicate improved function.

Mood and Anxiety Symptom Questionnaire (MASQ)4 weeks post-treatment

Questions designed to assess symptoms of general distress using a 5-point Likert scale ranging from 1"not at all" to 5 "extremely".

Trial Locations

Locations (1)

Ralph H. Johnson VA Medical Center, Charleston, SC

🇺🇸

Charleston, South Carolina, United States

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