Clinical trial NCT06214949: Personalized Repetitive Transcranial Magnetic Stimulation (PrTMS)
Official title: Personalized Repetitive Transcranial Magnetic Stimulation (PrTMS) as a Treatment for Chronic Neck Pain
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Neck Pain
Lead sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine
Sponsor class: OTHER
Collaborators: name: Uniformed Services University of the Health Sciences
name: Walter Reed National Military Medical Center
First posted: 2024-01-22
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to assess the efficacy of Personalized Repetitive Transcranial Magnetic Stimulation (PrTMS) therapy to reduce chronic neck for military health system beneficiaries.

Detailed description: 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)

Eligibility criteria: Inclusion Criteria:

* Military health care beneficiary for enrollment.
* Over the age of 18 years.
* Presence of chronic neck pain for at least 3 months.

Exclusion Criteria:

* History of seizure, bipolar disorder, or schizophrenia.
* Unstable heart or pulmonary disease.
* Brain tumor, active brain infection, history of cerebral vascular accident (CVA), or penetrating brain injury.
* Use of medications that potentially lower seizure threshold without concomitant administration of anticonvulsant drugs that may protect against seizure occurrence.

  1. Antiviral medications and antipsychotic medications
  2. Recent withdrawal from sedatives
  3. Substance abuse of phencyclidine, amphetamines, ketamine, and gammahydroxybutyrate
* Not a suitable candidate for the study as determined by the PI.
* Pregnancy, breastfeeding, or plans to become pregnant during the course of the study.
* Presence of metallic hardware in close contact to the discharging coil (e.g. cochlear implants, internal pulse generator).
* Presence of implanted brain electrodes (cortical or deep-brain electrodes).
* Potential participants who score above a certain suicide relevant survey score on the Suicide Behaviors Questionnaire-Revised (SBQ-R), or are judged by expert clinicians to be a serious risk of harm to self, will be excluded.
* Participants cannot have undergone a previous TMS treatment within the last 30 days before the start of study treatment.
* Participants must have reliable and consistent access to the internet to complete surveys when not present in the clinic.
* Participants must not have a clinical diagnosis of insomnia.
* Participants can not be actively partaking in a substance abuse program.

Primary outcomes:
measure: Defense & Veterans Pain Rating Scale (DVPRS)
timeFrame: 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
Secondary outcomes:
measure: Patient Global Impression of Change (PGIC)
timeFrame: 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
measure: TMS Tolerability Worksheet (TTW)
timeFrame: 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
measure: Pain Anxiety Symptom Scale Short Form 20 (PASS)
timeFrame: 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
measure: Sleep Condition Indicator (SCI)
timeFrame: 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
measure: Generalized Anxiety Disorder 7-item scale (GAD-7)
timeFrame: 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
measure: Patient Health Questionnaire (PHQ-9)
timeFrame: 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
measure: Quantitative Analgesic Questionnaire (QAQ)
timeFrame: 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
measure: Suicide Behaviors Questionnaire-Revised (SBQ-R)
timeFrame: 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
measure: PTSD Checklist for DSM-5 (PCL-5)
timeFrame: 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
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Scales.
timeFrame: 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
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: 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
measure: Insomnia Severity Index (ISI)
timeFrame: 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
measure: Demographics Survey
timeFrame: Taken at Baseline to create comparable groups of treatment and will be used as covariates in statistical analysis.
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
Study officials:
affiliation: Uniformed Services University of the Health Sciences
name: Oluwaseyi Gbade-Alabi, MD
role: PRINCIPAL_INVESTIGATOR
References: