H-coil TMS to Reduce Pain: A Pilot Study Evaluating Relative Efficacy of the H1 vs H7 Coil

Sponsor
Wake Forest University Health Sciences (Other)
Overall Status
Recruiting
CT.gov ID
NCT04203199
Collaborator
(none)
60
1
4
10.4
5.8

Study Details

Study Description

Brief Summary

Chronic pain is a serious public health problem with estimates as high as nearly half of the adult population experiencing some form of pain that lasts for more than 6 months. Chronic use of opiates is a rapidly escalating crisis in the United States, with over 4.3 million Americans dependent on opiate analgesics, an escalating rate of opiate overdose deaths, and a resurgence of intravenous heroin use leading to total societal cost exceeding $55 billion. While opiates are effective at treating acute pain, tolerance to the analgesic effects develops quickly, leading to high abuse liability and dependence potential. Consequently, the development of a new, non-pharmacologic intervention to treat pain, such as repetitive transcranial magnetic stimulation (rTMS), which would provide analgesic benefit while also directly remodeling the neural circuitry responsible for cognitive control over opiate craving, would fill an increasingly urgent public health need.

Condition or Disease Intervention/Treatment Phase
  • Device: Real rTMS to the mPFC using H7 Coil
  • Device: Sham rTMS to the mPFC using H7 Coil
  • Device: Real rTMS to the dlPFC using H1 Coil
  • Device: Sham rTMS to the dlPFC using H1 Coil
N/A

Detailed Description

Chronic pain is a serious public health problem with estimates as high as nearly half of the adult population experiencing some form of pain that lasts for more than 6 months. Chronic use of opiates is a rapidly escalating crisis in the United States, with over 4.3 million Americans dependent on opiate analgesics, an escalating rate of opiate overdose deaths, and a resurgence of intravenous heroin use leading to total societal cost exceeding $55 billion. While opiates are effective at treating acute pain, tolerance to the analgesic effects develops quickly, leading to high abuse liability and dependence potential. Consequently, the development of a new, non-pharmacologic intervention to treat pain, such as repetitive transcranial magnetic stimulation (rTMS), which would provide analgesic benefit while also directly remodeling the neural circuitry responsible for cognitive control over opiate craving, would fill an increasingly urgent public health need.

Acute pain is associated with elevated magnetic resonance imaging (MRI) blood-oxygen-level-dependent (BOLD) signal in targets of ascending nociceptive fibers including the insula, dorsal anterior cingulate (dACC), thalamus and somatosensory cortex - the 'Pain Network'. Perceived pain, and corresponding BOLD signal in the Pain Network, is attenuated by 10 Hz rTMS (a form of brain stimulation that results in long term potentiation (LTP) to the left dorsolateral prefrontal cortex (dlPFC, a node of the Executive Control Network). Dr. Borckardt was the first person to demonstrate that when LTP-like dlPFC rTMS was delivered in the postoperative recovery room, patients used less morphine in the hospital and require less morphine long-term. These analgesic effects are now widely known, with over 33 clinical trials utilizing rTMS as a tool to decrease acute and chronic pain in various clinical populations.

These data all suggest that LTP-like DLPFC rTMS is a very strong candidate alleviating chronic pain (LTP-like dlPFC rTMS (Strategy 1, Aim 1)). An alternative approach, however, which may also target opiate craving, is to attenuate the Pain Network (through long term depression (LTD) of the ventromedial PFC) (LTD-like mPFC rTMS, Strategy 2, Aim 1). In a cohort of 49 individuals with chronic pain, Dr. Hanlon (Primary Investigator) recently demonstrated that LTD-like mPFC rTMS reduced baseline BOLD signal in multiple regions of interest (ROIs) involved in craving which also overlap with the Pain Network (e.g. dACC and Insula). To parametrically evaluate these 2 promising treatment strategies, the investigator has developed a 1-visit cross-sectional design wherein a cohort of healthy control individuals will receive Quantitative Sensory Testing before and after rTMS with the H1 and H7-coil for dlPFC stimulation (Strategy 1) and mPFC depression (Strategy 2), respectively.

The investigator will also measure subjective pain ratings. The investigator aims to:

Aim 1. Quantify the effects of LTP-like and LTD-like RTMS on Quantitative Sensory Testing Hypothesis: The thermal pain tolerance of individuals in these two group will increase after one session of rTMS administered by the H1- and H7-coil design relative to sham.

Aim 2. Evaluate the effects of rTMS on subjective experience of discomfort. Hypothesis:

Subjective experience of discomfort will decrease relative to sham in individuals after one session of LTP-like or LTD-like rTMS administered to the dlPFC and mPFC, respectively.

The relative efficacy of Strategy 1 vs 2 will directly translate to development of a large clinical trial of rTMS as an innovative, new treatment option for pain in opiate dependent individuals.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
The proposed study will employ a 1-visit cross sectional, double-blind, placebo-controlled design to parametrically evaluate two promising treatment strategies of rTMS using the H1 and H7-coil for dlPFC stimulation (Strategy 1) or mPFC stimulation (Strategy 2), respectively. Participants will be randomized to receive TMS to the dlPFC, mPFC, or sham (50% at each site), using a Latin square randomization. This will be done in a cohort of healthy control individuals recruited from the local Wake Forest University (WFU) community. Quantitative Sensory Testing (QST) and subjective pain ratings will be measured before and after the rTMS session.The proposed study will employ a 1-visit cross sectional, double-blind, placebo-controlled design to parametrically evaluate two promising treatment strategies of rTMS using the H1 and H7-coil for dlPFC stimulation (Strategy 1) or mPFC stimulation (Strategy 2), respectively. Participants will be randomized to receive TMS to the dlPFC, mPFC, or sham (50% at each site), using a Latin square randomization. This will be done in a cohort of healthy control individuals recruited from the local Wake Forest University (WFU) community. Quantitative Sensory Testing (QST) and subjective pain ratings will be measured before and after the rTMS session.
Masking:
Double (Participant, Care Provider)
Primary Purpose:
Treatment
Official Title:
H-coil TMS to Reduce Pain: A Pilot Study Evaluating Relative Efficacy of the H1 vs H7 Coil
Actual Study Start Date :
Jan 18, 2022
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Real rTMS to the mPFC using H7 Coil

One session of low frequency repetitive transcranial magnetic stimulation (rTMS) will be delivered to the left medial prefrontal cortex (mPFC) using the H7-coil (20 min total, 1200 pulses delivered at 1 Hz continuously, 1 train, 120% resting motor threshold (rMT)).

Device: Real rTMS to the mPFC using H7 Coil
This will be delivered with the Brainsway H7 coil system; 1200 pulses with the H7 coil helmet. Blinded using active/sham operator cards.

Sham Comparator: Sham rTMS to the mPFC using H7 Coil

One session of sham low frequency repetitive transcranial magnetic stimulation (rTMS) will be delivered to the left medial prefrontal cortex (mPFC) using the H7-coil (sham rTMS - 20 min total, 1200 pulses delivered at 1 Hz continuously, 1 train, 120% resting motor threshold (rMT)).

Device: Sham rTMS to the mPFC using H7 Coil
Sham stimulation will be administered using 'sham cards' provided by the Brainsway system for the H1/H7 coil. The sham coil still administers scalp sensations and acoustic artifacts but does not produce a magnetic field. Therefore, this treatment delivers no TMS. The visit for the group receiving sham treatment will otherwise be identical to the real TMS groups.

Experimental: Real rTMS to the dlPFC using H1 Coil

One session of high frequency repetitive transcranial magnetic stimulation (rTMS) will be delivered to the left dorsolateral prefrontal cortex (dlPFC) using the H1-coil (20 min total, 3000 pulses delivered at 10 Hz, 60 trains, 50 pulses/train, 5 sec on/15 sec off, 120% resting motor threshold (rMT)).

Device: Real rTMS to the dlPFC using H1 Coil
This will be delivered with the Brainsway H1 coil system; 3000 pulses with the H1 coil helmet. Blinded using active/sham operator cards.

Sham Comparator: Sham rTMS to the dlPFC using H1 Coil

One session of sham high frequency repetitive transcranial magnetic stimulation (rTMS) will be delivered to the left dorsolateral prefrontal cortex (dlPFC) using the H1-coil (sham rTMS- 20 min total, 3000 pulses delivered at 10 Hz, 60 trains, 50 pulses/train, 5 sec on/15 sec off, 120% resting motor threshold (rMT)).

Device: Sham rTMS to the dlPFC using H1 Coil
Sham stimulation will be administered using 'sham cards' provided by the BrainsWay system for the H1/H7 coil. The sham coil still administers scalp sensations and acoustic artifacts but does not produce a magnetic field. Therefore, this treatment delivers no TMS. The visit for the group receiving sham treatment will otherwise be identical to the real TMS groups.

Outcome Measures

Primary Outcome Measures

  1. Changes in pain thresholds using the Quantitative Pain Testing (QST) Task, which utilizes thermal heat from the Medoc Pathway Thermode device to detect pain thresholds [rTMS treatment visit, an average of 2 and a half hours]

    Based on pilot data, the investigators expect an interaction between treatment (Real DLPFC or MPFC TMS vs. Sham) and time (Before vs. After rTMS) on reported painfulness using a quantitative sensory testing technique determines the sensation and pain thresholds of warm temperatures. Painfulness ratings will be assessed and reported before and after rTMS.

Secondary Outcome Measures

  1. Changes in Patient Self-Reported Pain and Discomfort [rTMS treatment visit, an average of 2 and a half hours]

    The investigators expect changes in self reported qualitative pain assessment via a numeric pain rating scale (ranging from 0 to 10, 10 being the most extreme pain) when comparing active vs sham. Pain rating values will be assessed before and after rTMS.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  1. Age 18 - 65 (to maximize participation).

  2. Does not have a history of and is currently not experiencing chronic pain.

  3. Able to read and understand questionnaires and informed consent.

  4. Lives within 50 miles of the study site.

  5. Is not at elevated risk of seizure (i.e., does not have a history of seizures, is not currently prescribed medications known to lower seizure threshold).

  6. Does not have a history of traumatic brain injury, including a head injury that resulted in hospitalization, loss of consciousness for more than 10 minutes, or having ever been informed that they have an epidural, subdural, or subarachnoid hemorrhage.

Exclusion Criteria:
  1. Any psychoactive illicit substance use (except marijuana and nicotine) within the last 30 days by self-report and urine drug screen. For marijuana, no use within the last seven days by verbal report and negative (or decreasing) urine THC levels.

  2. Meets DSM-V criteria for moderate substance dependence, current axis I disorders of major depression, panic disorder, obsessive-compulsive disorder, post traumatic stress syndrome, bipolar affective disorder, schizophrenia, dissociate disorders, eating disorders, and any other psychotic disorder.

  3. Has current suicidal ideation or homicidal ideation.

  4. Has the need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications and medications for ADHD.

  5. Females of childbearing potential who are pregnant (by urine HCG), nursing, or who are not using a reliable form of birth control.

  6. Has current charges pending for a violent crime (not including DUI related offenses).

  7. Suffers from chronic migraines.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Atrium Health Wake Forest Baptist Winston-Salem North Carolina United States 27157

Sponsors and Collaborators

  • Wake Forest University Health Sciences

Investigators

  • Principal Investigator: Colleen Hanlon, PhD, Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Wake Forest University Health Sciences
ClinicalTrials.gov Identifier:
NCT04203199
Other Study ID Numbers:
  • IRB00062742
First Posted:
Dec 18, 2019
Last Update Posted:
Apr 28, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
Yes
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by Wake Forest University Health Sciences
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 28, 2022