search
Back to results

rTMS for Emotional Difficulties in Verterans (rTMS)

Primary Purpose

Mental Health, Depression, rTMS

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Repetitive Transcranial Magnetic Stimulation (rTMS)
Sponsored by
VA Office of Research and Development
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mental Health focused on measuring Depression

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Ralph H. Johnson VA Medical Center, Charleston, SCRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Dose 1

Dose 2

Dose 3

Dose 4

Dose 5

Dose 6

Dose 7

Dose 8

Dose 9

Dose 10

Arm Description

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Inventory of Psychosocial Functioning (IPF)
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.
World Health Organization Quality of Life - Brief Form (WHOQOL-BF)
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.
Illness Intrusiveness Rating Scale (IIRS)
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

Neurocognitive performance
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.
Inventory of Depression and Anxious Symptoms (IDAS-II)
Questions are rated on a scale from 1-5 and covers a wide array of psychological measures
Hamilton Scale for Depression (HAM-D)
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.
Mood and Anxiety Symptom Questionnaire (MASQ)
Questions designed to assess symptoms of general distress using a 5-point Likert scale ranging from 1"not at all" to 5 "extremely".

Full Information

First Posted
November 19, 2018
Last Updated
August 9, 2023
Sponsor
VA Office of Research and Development
search

1. Study Identification

Unique Protocol Identification Number
NCT03749967
Brief Title
rTMS for Emotional Difficulties in Verterans
Acronym
rTMS
Official Title
Developing a Novel rTMS Intervention for Transdiagnostic Psychosocial Rehabilitation: A Dose Finding Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2019 (Actual)
Primary Completion Date
August 31, 2023 (Anticipated)
Study Completion Date
October 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development

4. Oversight

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
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mental Health, Depression, rTMS, Anxiety, PTSD, Psychosocial Impairment
Keywords
Depression

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
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.
Masking
Participant
Masking Description
All participants will be randomized to 10 different active doses of accelerated, intermittent theta burst rTMS.
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose 3
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose 4
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose 5
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose 6
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose 7
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose 8
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose 9
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose 10
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Repetitive Transcranial Magnetic Stimulation (rTMS)
Intervention Description
MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.
Primary Outcome Measure Information:
Title
Inventory of Psychosocial Functioning (IPF)
Description
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.
Time Frame
4 weeks post-treatment
Title
World Health Organization Quality of Life - Brief Form (WHOQOL-BF)
Description
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.
Time Frame
4 weeks post-treatment
Title
Illness Intrusiveness Rating Scale (IIRS)
Description
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.
Time Frame
4 weeks post-treatment
Secondary Outcome Measure Information:
Title
Neurocognitive performance
Description
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.
Time Frame
4 weeks post-treatment
Title
Inventory of Depression and Anxious Symptoms (IDAS-II)
Description
Questions are rated on a scale from 1-5 and covers a wide array of psychological measures
Time Frame
4 weeks post-treatment
Title
Hamilton Scale for Depression (HAM-D)
Description
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.
Time Frame
4 weeks post-treatment
Title
Mood and Anxiety Symptom Questionnaire (MASQ)
Description
Questions designed to assess symptoms of general distress using a 5-point Likert scale ranging from 1"not at all" to 5 "extremely".
Time Frame
4 weeks post-treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lisa M McTeague, PhD
Phone
(843) 577-5011
Email
Lisa.Mcteague@va.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lisa M. McTeague, PhD
Organizational Affiliation
Ralph H. Johnson VA Medical Center, Charleston, SC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ralph H. Johnson VA Medical Center, Charleston, SC
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29401-5703
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa M McTeague, PhD
Phone
843-577-5011
Email
Lisa.Mcteague@va.gov
First Name & Middle Initial & Last Name & Degree
Lisa M. McTeague, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

rTMS for Emotional Difficulties in Verterans

We'll reach out to this number within 24 hrs