Project Relief: Developing Brain Stimulation as a Treatment for Chronic Pain

NCT04156802 | Completed Results DMC FDA Device

• 1 other identifier: IRB00061967
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Effective control of chronic pain is a top priority in the United States, as approximately 10% of adults have severe chronic pain most of which is chronic lower back pain (CLBP). However, despite the advances in neuroscience over the past 20 years, chronic pain is largely treated with opiate narcotics, much as was done in the Civil War. In addition to their high abuse liability and dependence potential, only 30 40% of chronic pain patients declare they receive satisfactory (\>50%) relief from their pain through pharmacological treatment. In these patients a common clinical practice is to escalate the dose of opiates as tolerance develops which unfortunately has contributed to escalation in opiate overdose deaths, a resurgence of intravenous heroin use, and $55 billion in societal costs. Consequently, there is a critical need for new treatments that can treat pain and reduce reliance on opiates in individuals with chronic pain. The proposed study will be the first to employ a randomized, double-blind, sham-controlled design to parametrically evaluate the longitudinal effects of 16 days of Repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex (MC) or the medial prefrontal cortex (MPFC) on self-reported pain and the brain s response to pain. This will be done in a cohort of patients recruited from the community as well as Wake Forest Baptist Health (WFBH) clinics with chronic lower back pain that have not been able to find adequate pain relief, whether or not they are using prescription opiates for 3 or more months. Participants will be randomized to receive rTMS to the MC, MPFC, or sham (50% at each site), using a Latin square randomization. Resting state connectivity will be collected 3 times: before the 1st day of TMS, after the 12th day of TMS, and before the 16th day of TMS (the last day administered).

Conditions

Chronic Pain; Chronic Lower Back Pain; Back Pain; Opioid Use; Opiate Dependence; Pain, Chronic; Neuropathic Pain; Chemotherapy-induced Peripheral Neuropathy

Keywords

Transcranial Magnetic Stimulation; Brain Stimulation; Treatment; Neuroimaging; Alternative

Outcome Measures

Primary Outcomes (1)

• Changes in Patient Reported Pain and Discomfort

  The investigators expect changes in self reported qualitative pain assessment via a numeric pain rating scale when comparing active vs sham. Pain rating values will be assessed and reported through the duration of the study. Percent change from baseline values ranged from -100 to 500. Larger, positive values represent increased pain and worse outcomes.

  From Baseline to the last follow up session (16 weeks)

Other Outcomes (2)

• Changes in Pain Thresholds Using the Quantitative Pain Testing (QST) Task, Which Utilizes Pressure From the Medoc Pathway Algomed Device to Detect Pain Thresholds

  Through study completion, an average of 4 and a half months

• Neuroimaging Outcomes: Changes in the Brain's Response to Pain as Specified by Changes in BOLD Signal

  Through study completion, an average of 4 and a half months

Study Arms (4)

Real TBS to the mPFC

EXPERIMENTAL

Two sessions of real Theta Burst Stimulation (TBS) will be delivered to the medial prefrontal cortex (mPFC) over the course of the treatment and maintenance phase of the study

Device: Real TBS to the mPFC

Sham TBS to the mPFC

SHAM COMPARATOR

Two sessions of sham Theta Burst Stimulation (TBS) will be delivered to the medial prefrontal cortex (mPFC) over the course of the treatment and maintenance phase of the study

Device: Sham TBS to the mPFC

Real TBS to the MC

EXPERIMENTAL

Two sessions of real Theta Burst Stimulation (TBS) will be delivered to the somatomotor cortex (MC) over the course of the treatment and maintenance phase of the study

Device: Real TBS to the MC

Sham TBS to the MC

SHAM COMPARATOR

Two sessions of sham Theta Burst Stimulation (TBS) will be delivered to the somatomotor cortex (MC) over the course of the treatment and maintenance phase of the study

Device: Sham TBS to the MC

Interventions

Real TBS to the mPFC DEVICE

This will be delivered with the Magventure Magpro system; 600 pulses with the active sham coil (double blinded)

Real TBS to the mPFC

Sham TBS to the mPFC DEVICE

This will be delivered with the Magventure Magpro system; 600 pulses with the active sham coil (double blinded). The MagVenture MagPro system has an integrated active sham that passes current through two surface electrodes placed on the skin beneath the coil.

Sham TBS to the mPFC

Real TBS to the MC DEVICE

This will be delivered with the Magventure Magpro system (double blinded).

Real TBS to the MC

Sham TBS to the MC DEVICE

This will be delivered with the Magventure Magpro system (double blinded). The MagVenture MagPro system has an integrated active sham that passes current through two surface electrodes placed on the skin beneath the coil.

Sham TBS to the MC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 (to maximize participation)
• Can currently be using prescription opiates
• Able to read and understand questionnaires and informed consent.
• 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 metal objects in the head/neck.
• 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.
• Does not have a history of claustrophobia leading to significant clinical anxiety symptoms.

You may not qualify if:

• Any psychoactive illicit substance use (except marijuana and nicotine) within the last 30 days by self-report and urine drug screen.
• Meets DSM V criteria for current axis I disorders of obsessive-compulsive disorder, bipolar affective disorder, schizophrenia, dissociate disorders, eating disorders, and any other psychotic disorder or organic mental 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).
• Does not have a stable living situation.
• Suffers from chronic migraines.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

Study Sites (1)

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, 27101, United States

Location

MeSH Terms

Conditions

Chronic Pain; Back Pain; Opioid-Related Disorders; Neuralgia

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases

Results Point of Contact

• Title: Merideth Addicott, PhD
• Organization: Wake Forest University School of Medicine

maddicot@wakehealth.edu

336-716-7792

Study Officials

• Merideth A Addicott, PhD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This randomized, double-blind, sham-controlled study will parametrically evaluate the longitudinal effects of 16 days of rTMS to the MC (Aim 1) or the MPFC (Aim 2) on self-reported pain and the brain's response to pain. This will be done in a cohort of patients recruited from Wake Forest University clinics and the outer community with chronic lower back pain that may or may not be using prescription opiates for 3 or more months without adequate pain relief. Participants will be randomized to receive TMS to the MC, MPFC,or sham (50% at each site), using a Latin square randomization. Resting state connectivity will be collected. Quantitative Pain Testing will be collected 11 times. MRI data will be collected 3 times: before the 1st visit of TMS, after the 12th visit of TMS, and after the 16th visit of TMS.

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 8, 2019
• Study Start: June 15, 2020
• Primary Completion: July 6, 2022
• Study Completion: July 6, 2022
• Last Updated: May 12, 2023
• Results First Posted: May 12, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)