This study aims to assess the efficacy of Personalized Repetitive Transcranial Magnetic Stimulation (PrTMS) therapy to reduce chronic neck for military health system beneficiaries.
The objective of our proposed research is to (a) assess the efficacy of PrTMS therapy in reducing pain for military health system beneficiaries with chronic neck pain receiving standard of care\* at Walter Reed National Military Medical Center, and (b) to describe participants' perceptions of PrTMS treatment and its perceived effect on their pain. The specific aims for this study are as follows: Specific Aims Aim 1a: To assess the efficacy of PrTMS therapy in reducing pain for military health system beneficiaries with chronic neck pain receiving standard of care at Walter Reed National Military Medical Center. Aim 1b: To describe participants' perceptions of PrTMS treatment and its perceived effect on their pain. Hypothesis 1a: Participants receiving PrTMS therapy in addition to standard of care will report a significant mean reduction in their pain based on quantitative and qualitative assessments, when compared to standard of care plus sham PrTMS. Hypothesis 1b: Participant response to PrTMS will be independent of patient demographics (age, race, sex), length of chronic pain, characterization of type of pain (e.g., sharp, burning, aching, etc.), or location of pain (e.g., local vs. radiating). Outcome Measures: DVPRS summary pain score and four supplemental questions, measuring activity, sleep, mood, and stress. Aim 2: To examine the short- and intermediate-term changes in self-reported quality of life and biopsychosocial symptoms related to pain in military health system beneficiaries receiving PrTMS in addition to standard of care for chronic neck pain at Walter Reed National Military Medical Center. Hypothesis 2: Participants receiving PrTMS therapy will report significantly lower mean scores on PROMIS (fatigue, pain interference, and social isolation) and sleep disturbance, and higher mean PROMIS (physical function and satisfaction with social roles) than participants receiving sham PrTMS across the intervention period and at follow up. Outcome Measures: The National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS) measures are validated, global measures of patient-reported outcomes with standardized scales and computer adaptive testing (CAT). CAT allows for reduced participant burden, as the number of questions asked to arrive at a score are fewer. PROMIS measures have also been recommended as an assessment tool for studies conducted exploring TMS as treatment for pain. To measure the biopsychosocial elements of pain, the following PROMIS measures will be utilized: 1. PROMIS Bank v1.0 - Fatigue 2. PROMIS Bank v1.1 - Pain Interference 3. PROMIS Bank v2.0 - Physical Function 4. PROMIS Bank v2.0 - Satisfaction with Social Roles 5. PROMIS Bank v1.0 - Social Isolation Aim 3: To assess the impact that confounding factors such as depression, anxiety, sleep disorders, or PTSD may have on the efficacy of PrTMS as an augmentation to standard of care. Hypothesis 3: Participants that have high premorbid levels of mental health disease or sleep disturbances will exhibit less response to PrTMS than those who do not. Outcome Measures: PCL-5, PHQ-9, SCI, GAD-7 and OURA ring. (see section 10.2) Aim 4: To assess the short- and intermediate-term changes in plasma neuropeptides, inflammatory proteins and nucleic acids that can serve as blood based biomarkers for pain /stress. Hypothesis 4: Participants receiving PrTMS therapy will demonstrate significantly lower mean plasma concentrations of tested plasma neuropeptides and inflammatory proteins, as well as associated genetic markers, including mRNA, miRNA, and genomic sequences. Biological Blood and Serum Measures: Neuropeptides such as ACTH, NPY, IGF-1, BDNF, NSE, GFAP, S100B; inflammatory proteins, such as IL-1beta, IL-2, IL-6, IL-8, IL-10, IL-12, TNF-alpha, IFN-gamma, MCP1/CCL2, CRP; mRNA; miRNA; and whole genome sequencing (WGS)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
120
Treatment will consist of 15 sessions over 3-4 weeks. Specifically, the active or sham treatments will be conducted \~5 times a week during the treatment phase of the study. The treatment protocol parameters (stimulus location, frequency, duration, and intensity) will be derived from the PrTMS software algorithm which incorporates clinical inputs from neurocognitive surveys and quantitative EEG analysis. The mechanical parameters will adhere to the recommended PrTMS parameters for pain treatment: figure of 8 coil that produces biphasic stimulatory pulses to the central zone cortex, frontal zone cortex, Broca's area, and frontal pre-cortex areas at a stimulation depth of 2 cm. Treatment parameters will be unique to each participant but will remain within known ranges. The frequency will be between 8 and 13 Hz, at an amplitude of 20-30% (approximately 30-40% of RMT), and about 3200-7200 pulses per session. Since parameters are specific to each participant, treatment settings will vary.
Treatment will consist of 15 sessions over the course of 3-4 weeks. More specifically, the active or sham treatments will be conducted roughly 5 times a week during the course of the treatment phase of the study. The TMS system will have three coils, one designated active and the other two unlabeled and identical in appearance, weight, and noises emitted, one of which will be active and one of which will be sham.
Walter Reed National Military Medical Center
Bethesda, Maryland, United States
RECRUITINGDefense & Veterans Pain Rating Scale (DVPRS)
The DVPRS was developed to standardize pain measurement across all health care settings and promote pain assessment and reassessment practices. DVPRS is a visual pain scale to assess individual's pain intensity on a scale of 0-10, with an additional 4 questions to assess pain's interference with the participant's activity, sleep, mood, and stress. The scale has excellent internal reliability and test-retest reliability.
Time frame: Measured to compare changes from Baseline; during Phase 1 and 2 of treatment; and during the follow up phase after treatment ends up to 8 weeks. Measurements taken everyday during Baseline, Phase 1 and Phase 2 and at 2, 4, and 8 weeks in Follow-Up
Patient Global Impression of Change (PGIC)
The PGIC outcome measure evaluates a patient's self-reported level of pain and their feelings about treatment effectiveness to determine symptom improvement using a 7 point scale from 1-7. Higher scores indicate a greater improvement while lower scores indicate less improvement or even worsening of a condition.
Time frame: Measured to compare changes from Baseline; during Phase 1 and 2 of treatment; and during the follow up phase after treatment ends up to 8 weeks. Measurements will be taken once at end of Baseline, Phase 1 and Phase 2 and at 2, 4, and 8 weeks in Follow-Up
TMS Tolerability Worksheet (TTW)
The TTW is administered after each PrTMS session to accurately track and record tolerability of TMS therapy as well as frequency and severity of the known minor negative side effects of TMS, such as headaches.
Time frame: Measured to compare changes from Baseline; during Phase 1 and 2 of treatment; and during the follow up phase after treatment ends up to 8 weeks. Measurements will be taken once at end of Baseline, Phase 1 and Phase 2 and at 2, 4, and 8 weeks in Follow-Up
Pain Anxiety Symptom Scale Short Form 20 (PASS)
The PASS measures anxiety and fear specifically related to pain on a scale from 0 (never) to 5 (always).
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Time frame: Measured to compare changes from Baseline; during Phase 1 and 2 of treatment; and during the follow up phase after treatment ends up to 8 weeks. Measurements will be taken once at end of Baseline, Phase 1 and Phase 2 and at 2, 4, and 8 weeks in Follow-Up
Sleep Condition Indicator (SCI)
The SCI is an 8-item self-report measure that evaluates insomnia disorder where answers to a given item are weighted from 0 (affected sleep) to 4 (no affected sleep). A higher score is indicative of better sleep.
Time frame: Measured to compare changes from Baseline; during Phase 1 and 2 of treatment; and during the follow up phase after treatment ends up to 8 weeks. Measurements will be taken once at end of Baseline, Phase 1 and Phase 2 and at 2, 4, and 8 weeks in Follow-Up
Generalized Anxiety Disorder 7-item scale (GAD-7)
The GAD-7 is a 7-item self-report measure that assesses an individual's level of anxiety on daily life using a scale from 0 (Not at all) to 3 (Nearly every day). Higher scores indicate higher levels of anxiety.
Time frame: Measured to compare changes from Baseline; during Phase 1 and 2 of treatment; and during the follow up phase after treatment ends up to 8 weeks. Measurements will be taken once at end of Baseline, Phase 1 and Phase 2 and at 2, 4, and 8 weeks in Follow-Up
Patient Health Questionnaire (PHQ-9)
The (PHQ-9) is a 9-item measure of depression through affect on everyday life on a scale of 0 (Not at all) to 3 (Nearly every day). Higher scores are indicative of higher levels of depression.
Time frame: Measured to compare changes from Baseline; during Phase 1 and 2 of treatment; and during the follow up phase after treatment ends up to 8 weeks. Measurements will be taken once at end of Baseline, Phase 1 and Phase 2 and at 2, 4, and 8 weeks in Follow-Up
Quantitative Analgesic Questionnaire (QAQ)
The QAQ is a tool used to identify and comprehensively document medication use and adherence to prescriptions based on patient self-reports.
Time frame: Measured to compare changes from Baseline; during Phase 1 and 2 of treatment; and during the follow up phase after treatment ends up to 8 weeks. Measurements will be taken once at end of Baseline, Phase 1 and Phase 2 and at 2, 4, and 8 weeks in Follow-Up
Suicide Behaviors Questionnaire-Revised (SBQ-R)
The SBQ-R is a self-report questionnaire targeted to assess suicidal risk factors in individuals aged 13 and older. Responses will be scored based on how participants respond with values between 1 and 6 points. Higher scores are more indicative of suicidal risk.
Time frame: Measured to compare changes from Baseline; during Phase 1 and 2 of treatment; and during the follow up phase after treatment ends up to 8 weeks. Measurements will be taken once at end of Baseline, Phase 1 and Phase 2 and at 2, 4, and 8 weeks in Follow-Up
PTSD Checklist for DSM-5 (PCL-5)
The PCL-5 is a self-report questionnaire on the presence and severity of PTSD symptoms. Responses range from values of 0 (Not at all) to 4 (Extremely) where higher scores are more indicative of severe PTSD.
Time frame: Measured to compare changes from Baseline; during Phase 1 and 2 of treatment; and during the follow up phase after treatment ends up to 8 weeks. Measurements will be taken once at end of Baseline, Phase 1 and Phase 2 and at 2, 4, and 8 weeks in Follow-Up
Patient Reported Outcomes Measurement Information System (PROMIS) Scales.
The PROMIS scales will be used in this study to examine effects of TMS on quality of life using the following scales: Fatigue, Pain Interference, Physical Function, Satisfaction with Social Roles, and Social Isolation. Responses will vary from Never (scored as 0) to Always (scored as 4). Higher scores being more indicative of the concept being measured.
Time frame: Measured to compare changes from Baseline; during Phase 1 and 2 of treatment; and during the follow up phase after treatment ends up to 8 weeks. Measurements will be taken once at end of Baseline, Phase 1 and Phase 2 and at 2, 4, and 8 weeks in Follow-Up
Pittsburgh Sleep Quality Index (PSQI)
The PSQ-I is an effective instrument used to measure the quality and patterns of sleep in adults. Responses to questions about sleep will be scored from 0 (better sleep quality) to 3 (worse sleep quality). Higher overall scores being indicative of lower quality of sleep.
Time frame: Measured to compare changes from Baseline; during Phase 1 and 2 of treatment; and during the follow up phase after treatment ends up to 8 weeks. Measurements will be taken once at end of Baseline, Phase 1 and Phase 2 and at 2, 4, and 8 weeks in Follow-Up
Insomnia Severity Index (ISI)
The ISI is a 7-item measure designed to briefly assess the severity of both nighttime and daytime insomnia symptoms. Responses will vary from Not at all (scored as 0) to Very Much (score as 4). Higher scores being indicative of increasing level of insomnia.
Time frame: Measured to compare changes from Baseline; during Phase 1 and 2 of treatment; and during the follow up phase after treatment ends up to 8 weeks. Measurements will be taken once at end of Baseline, Phase 1 and Phase 2 and at 2, 4, and 8 weeks in Follow-Up
Demographics Survey
Demographics and Health Questionnaires has questions pertinent to this research effort, including: age, sex, relationship status, race/ethnicity, education, military service, deployment history, health history, current and prior treatments.
Time frame: Taken at Baseline to create comparable groups of treatment and will be used as covariates in statistical analysis.