HealthyNCT04203199
H-coil TMS to Reduce Pain: A Pilot Study Evaluating Relative Efficacy of the H1 vs H7 Coil
A study testing Real rTMS to the mPFC using H7 Coil and Real rTMS to the dlPFC using H1 Coil in people with Healthy and Chronic Pain, run by Wake Forest University Health Sciences at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy, Chronic Pain, Opioid Use
- What is being tested?
- Real rTMS to the mPFC using H7 Coil and Real rTMS to the dlPFC using H1 Coil
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jan 2022to 6 Oct 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18 - 65 (to maximize participation).
- Does not have a history of and is currently not experiencing chronic pain.
- Able to read and understand questionnaires and informed consent.
- Lives within 50 miles of the study site.
- 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).
- 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.
Who cannot join
- 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.
- 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.
- Has current suicidal ideation or homicidal ideation.
- Has the need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications and medications for ADHD.
- Females of childbearing potential who are pregnant (by urine HCG), nursing, or who are not using a reliable form of birth control.
- Has current charges pending for a violent crime (not including DUI related offenses).
- Suffers from chronic migraines.
Trial locations and contacts
1 site in 1 country.
United States1 site
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, 27157
About this study
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.
Read the 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 aims to:
Aim 1. Quantify the effects of LTP-like and LTD-like RTMS on Quantitative Sensory Testing Hypothesis: The pressure pain tolerance of individuals in these two groups will increase after one session of rTMS administered by the H1- and H7-coil design.
Aim 2. Evaluate the effects of rTMS on subjective experience of discomfort. Hypothesis: Subjective experience of discomfort will decrease 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.
- Conditions
- Healthy, Chronic Pain, Opioid Use, Pain, Chronic
- Being tested
- Real rTMS to the mPFC using H7 Coil, Real rTMS to the dlPFC using H1 Coil
- Keywords
- Transcranial Magnetic Stimulation, Brain Stimulation, Healthy controls, Treatment
- Medical subject headings
- Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Real rTMS to the mPFC using H7 CoilDevice
This will be delivered with the Brainsway H7 coil system; 1200 pulses with the H7 coil helmet. Blinded using active/sham operator cards.
Real rTMS to the dlPFC using H1 CoilDevice
This will be delivered with the Brainsway H1 coil system; 3000 pulses with the H1 coil helmet. Blinded using active/sham operator cards.
| Study group | Role | What they receive |
|---|---|---|
| First H1 coil, then H7 coil | Experimental | There will be 1 screening and 2 TMS visits. The procedures will be identical for each TMS visit, except for the type of TMS delivered (H1 or H7 coil). Each participant will be assigned to both coils, with TMS type. Participants assigned to this arm will receive the H1 coil at TMS visit 1, H7 coil at TMS visit 2 Receives: Device: Real rTMS to the mPFC using H7 Coil; Device: Real rTMS to the dlPFC using H1 Coil |
| First H7 coil, then H1 coil | Experimental | There will be 1 screening and 2 TMS visits. The procedures will be identical for each TMS visit, except for the type of TMS delivered (H1 or H7 coil). Each participant will be assigned to both coils, with TMS type. Participants assigned to this arm will receive the H7 coil at TMS visit 1, H1 coil at TMS visit 2. Receives: Device: Real rTMS to the mPFC using H7 Coil; Device: Real rTMS to the dlPFC using H1 Coil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Painfulness Thresholds Using the Quantitative Pain Testing (QST) Task, Which Utilizes Pressure From the Medoc Algomed Device (Measured in kiloPascals).
Based on pilot data, the investigators expect an interaction between treatment (DLPFC or MPFC TMS) and time (Before vs. After rTMS) on reported painfulness using a quantitative sensory testing technique which determines the sensation and pain thresholds of pressure. Painfulness ratings will be assessed and reported before and after rTMS.
Measured: rTMS treatment visit, an average of 2 and a half hours
Secondary outcomes (1)
Changes in Pain Tolerance Thresholds Using the Quantitative Pain Testing (QST) Task, Which Utilizes Pressure From the Medoc Algomed Device (Measured in kiloPascals).
The investigators do not expect an interaction between treatment (DLPFC or MPFC TMS) and time (Before vs. After rTMS) on pain tolerance thresholds using a quantitative sensory testing technique which determines the sensation and pain thresholds of pressure. Pain tolerance ratings will be assessed and reported before and after rTMS.
Measured: rTMS treatment visit, an average of 2 and a half hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2019
- Study start18 Jan 2022
- Primary completion6 Oct 2022
- Study completion6 Oct 2022
Why it stopped: PI left institution
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 or mPFC (50% at each site). 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 blind
- Who is masked
- Participant, Care provider
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Colleen Hanlon, PhD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04203199
- Sponsor's protocol ID
- IRB00062742
- Status last verified
- Apr 2022
- First submitted
- 16 Dec 2019
- Last updated
- 15 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- H-coil TMS to Reduce Pain: A Pilot Study Evaluating Relative Efficacy of the H1 vs H7 Coil
- ClinicalTrials.gov ID
- NCT04203199
- Acronym / sponsor ID
- IRB00062742
- Conditions
- Healthy, Chronic Pain, Opioid Use, Pain, Chronic
- Keywords
- Transcranial Magnetic Stimulation, Brain Stimulation, Healthy controls, Treatment
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI left institution
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- 18 Jan 2022 (actual)
- Primary completion
- 6 Oct 2022 (actual)
- Study completion
- 6 Oct 2022 (actual)
- First posted
- 18 Dec 2019 (actual)
- Results
- Posted 15 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 aims to:
Aim 1. Quantify the effects of LTP-like and LTD-like RTMS on Quantitative Sensory Testing Hypothesis: The pressure pain tolerance of individuals in these two groups will increase after one session of rTMS administered by the H1- and H7-coil design.
Aim 2. Evaluate the effects of rTMS on subjective experience of discomfort. Hypothesis: Subjective experience of discomfort will decrease 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- 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 or mPFC (50% at each site). 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.
| Arm | Type | Receives |
|---|---|---|
| First H1 coil, then H7 coil | Experimental | Device: Real rTMS to the mPFC using H7 Coil, Device: Real rTMS to the dlPFC using H1 CoilThere will be 1 screening and 2 TMS visits. The procedures will be identical for each TMS visit, except for the type of TMS delivered (H1 or H7 coil). Each participant will be assigned to both coils, with TMS type. Participants assigned to this arm will receive the H1 coil at TMS visit 1, H7 coil at TMS visit 2 |
| First H7 coil, then H1 coil | Experimental | Device: Real rTMS to the mPFC using H7 Coil, Device: Real rTMS to the dlPFC using H1 CoilThere will be 1 screening and 2 TMS visits. The procedures will be identical for each TMS visit, except for the type of TMS delivered (H1 or H7 coil). Each participant will be assigned to both coils, with TMS type. Participants assigned to this arm will receive the H7 coil at TMS visit 1, H1 coil at TMS visit 2. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18 - 65 (to maximize participation).
- Does not have a history of and is currently not experiencing chronic pain.
- Able to read and understand questionnaires and informed consent.
- Lives within 50 miles of the study site.
- 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).
Key exclusion criteria (7 listed)
- 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.
- 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.
- Has current suicidal ideation or homicidal ideation.
- Has the need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications and medications for ADHD.
- Females of childbearing potential who are pregnant (by urine HCG), nursing, or who are not using a reliable form of birth control.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Real rTMS to the mPFC using H7 CoilThis will be delivered with the Brainsway H7 coil system; 1200 pulses with the H7 coil helmet. Blinded using active/sham operator cards. | Device | First H1 coil, then H7 coil, First H7 coil, then H1 coil |
| Real rTMS to the dlPFC using H1 CoilThis will be delivered with the Brainsway H1 coil system; 3000 pulses with the H1 coil helmet. Blinded using active/sham operator cards. | Device | First H1 coil, then H7 coil, First H7 coil, then H1 coil |
Primary outcome
Changes in Painfulness Thresholds Using the Quantitative Pain Testing (QST) Task, Which Utilizes Pressure From the Medoc Algomed Device (Measured in kiloPascals).
Time frame: rTMS treatment visit, an average of 2 and a half hours
Based on pilot data, the investigators expect an interaction between treatment (DLPFC or MPFC TMS) and time (Before vs. After rTMS) on reported painfulness using a quantitative sensory testing technique which determines the sensation and pain thresholds of pressure. Painfulness ratings will be assessed and reported before and after rTMS.
1 secondary outcome
Changes in Pain Tolerance Thresholds Using the Quantitative Pain Testing (QST) Task, Which Utilizes Pressure From the Medoc Algomed Device (Measured in kiloPascals).
Time frame: rTMS treatment visit, an average of 2 and a half hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Colleen Hanlon, PhD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Real rTMS to the mPFC using H7 Coil and Real rTMS to the dlPFC using H1 Coil in people with Healthy and Chronic Pain, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Painfulness Thresholds Using the Quantitative Pain Testing (QST) Task, Which Utilizes Pressure From the Medoc Algomed Device (Measured in kiloPascals). (time frame: rTMS treatment visit, an average of 2 and a half hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2023.