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Developing rTMS Treatment Strategies for Pain in Opiate Dependence

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ClinicalTrials.gov Identifier: NCT03576781
Recruitment Status : Recruiting
First Posted : July 3, 2018
Last Update Posted : July 23, 2019
Sponsor:
Collaborator:
South Carolina Clinical & Translational Research Institute (SCTR)
Information provided by (Responsible Party):
Medical University of South Carolina

Brief Summary:
The purpose of this study is to parametically evaluate two different types of repetitive Transcranial Magnetic Stimulation (rTMS) treatment strategies as a potential treatment for pain in individuals currently taking prescription opiates. Repetitive TMS is a non-invasive tool that uses magnetic pulses to temporarily stimulate specific brain areas. This study will test whether rTMS over different locations of the prefrontal cortex can produce a reduction in an individuals perception of pain and how the brain responds to pain. Participants will be randomized to receive either sham-rTMS, or one of two real rTMS treatments. Brain imaging, behavioral assessments, and pain assessments will be collected both immediately before and after rTMS.

Condition or disease Intervention/treatment Phase
Pain Chronic Pain Opioid Dependence Opioid Use Device: Real iTBS Device: Sham iTBS Device: Real cTBS Device: Sham cTBS Early Phase 1

Detailed Description:

Chronic use of opiates is a rapidly escalating crisis in the United States, with over 4.3 million Americans dependent on opiate analgesic, an escalating rate of opiate overdose deaths, and a resurgence of intravenous heroin use leading to total societal cost exceeding $55 billion. The struggle to break the addiction cycle is likely due to factors that affect neural circuits that govern craving and cognitive control. There is growing interest in the utilization of prefrontal cortex repetitive transcranial magnetic stimulation (rTMS) as a novel, non-invasive, non-pharmacologic approach to decreasing craving among chronic opiate users. At this early stage of development, however, it is unclear if the best TMS strategy is to (Strategy 1, Aim 1) increase activity in the dorsolateral prefrontal cortex, or (Strategy 2, Aim 2) decrease activity in the ventromedial prefrontal cortex.

DESIGN: To parametrically evaluate these two promising treatment strategies, the investigators have developed a design where opiate dependent individuals and healthy controls will be randomized to receive either one placebo-like TMS treatment, or one of two real TMS treatments (DLPFC iTBS or MPFC cTBS). Participants with opiate dependence will be recruited from the local community, as well as the MUSC Center for Drug and Alcohol Programs (CDAP), the Ralph H. Johnson Substance Abuse Treatment Center and local pain clinics. Healthy controls will be recruited from the local community. Approved Study Team Members will visit the above mentioned clinics and community and talk with patients. Individuals who consent will receive interleaved TMS/BOLD imaging and our established MRI-based thermal pain paradigm immediately before and after rTMS. The investigators will also measure subjective pain and opiate craving ratings. 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Developing Brain Stimulation as a Treatment for Pain in Opiate Dependent Individuals: Parametric Assessment of 2 Evidence-based Strategies
Actual Study Start Date : February 9, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Real iTBS to the DLPFC
One session of real intermittent Theta Burst Stimulation (iTBS) will be delivered to the left dorsolateral prefrontal cortex (dlPFC) (20 trains of stimulation over dlPFC (middle frontal gyrus) (F3); each train: 3 pulse bursts presented at 5Hz, 15 pulses/sec for 2 sec, 8 sec rest, 200 pulses/train; 110% RMT, MagPro; 600 pulses total)
Device: Real iTBS
This will be delivered with the Magventure Magpro system; 600 pulses with the active sham coil (double blinded using the USB key)

Sham Comparator: Sham iTBS to the DLPFC
One session of sham intermittent Theta Burst Stimulation (iTBS) will be delivered to the left dorsolateral prefrontal cortex (dlPFC) (20 trains of stimulation over dlPFC (middle frontal gyrus) (F3); each train: 3 pulse bursts presented at 5Hz, 15 pulses/sec for 2 sec, 8 sec rest, 200 pulses/train; 110% RMT, MagPro; 600 pulses total)
Device: Sham iTBS
This will be delivered with the Magventure Magpro system; 600 pulses with the active sham coil (double blinded using the USB key). The MagVenture MagPro system has an integrated active sham that passes current through two surface electrodes placed on the skin beneath the B60 coil.

Experimental: Real cTBS to the MPFC
One session of real continuous Theta Burst Stimulation (cTBS) will be delivered to the left medial prefrontal cortex (mPFC) (1 train of stimulation over the left frontal pole (FP1); each train: 3 pulse bursts presented at 5Hz, 15 pulses/sec for 40 sec, 600 pulses/train, 110% RMT, MagPro; 600 pulses total)
Device: Real cTBS
This will be delivered with the Magventure Magpro system; 600 pulses with the active sham coil (double blinded using the USB key).

Sham Comparator: Sham cTBS to the MPFC
One session of sham continuous Theta Burst Stimulation (cTBS) will be delivered to the left medial prefrontal cortex (mPFC) (1 train of stimulation over the left frontal pole (FP1); each train: 3 pulse bursts presented at 5Hz, 15 pulses/sec for 40 sec, 600 pulses/train, 110% RMT, MagPro; 600 pulses total)
Device: Sham cTBS
This will be delivered with the Magventure Magpro system; 600 pulses with the active sham coil (double blinded using the USB key). The MagVenture MagPro system has an integrated active sham that passes current through two surface electrodes placed on the skin beneath the B60 coil.




Primary Outcome Measures :
  1. iTBS to the left DLPFC vs. cTBS to the left MPFC [ Time Frame: Day 1 ]
    The effect of real vs. sham iTBS to the left DLPFC vs. real vs. sham cTBS to the left MPFC as a tool to modulate the brain response to pain will be assessed by comparing the brain activity in the executive circuit and limbic circuit before and after TMS.


Secondary Outcome Measures :
  1. Changes in pain threshold [ Time Frame: Day 1 ]
    The Quantitative Sensory pain assessment produces 3 output variables: sensory threshold, pain threshold, tolerance threshold (expressed in degrees Celsius). The pain thresholds for individuals that receive both DLPFC and MPFC will be tested using a within subject repeated measures design (time x treatment) wherein time is the repeated variable and Real or Sham TMS is the grouping variable.

  2. Changes in opiate pain and craving inventory [ Time Frame: Day 1 ]
    The Opiate Pain and Craving inventory produces 4 output variables of interest: level of discomfort, level of pain, urge to use opiates, amount willing to pay for an opiate. This will be tested using a within subject repeated measures design (time x treatment) wherein time is the repeated variable and Real or Sham TMS is the grouping variable.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Able to read and understand questionnaires and informed consent.
  2. Able to read and understand questionnaires and informed consent.
  3. Lives within 50 miles of the study site.
  4. 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)
  5. Does not have metal objects in the head/neck.
  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.
  7. Does not have a history of claustrophobia leading to significant clinical anxiety symptoms.

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 IV criteria for 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 or organic mental 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. Does not have a stable living situation.
  8. Suffers from chronic migraines.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03576781


Contacts
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Contact: Colleen A Hanlon, PhD 843-792-5732 hanlon@musc.edu
Contact: Logan Dowdle, BS 843-792-1442 dowdlel@musc.edu

Locations
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United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Colleen A Hanlon, PhD    843-792-5732    hanlon@musc.edu   
Ralph H Johnson Veterans Medical Center Recruiting
Charleston, South Carolina, United States, 29425
Contact: Colleen A Hanlon, PhD    843-792-5732    hanlon@musc.edu   
Sponsors and Collaborators
Medical University of South Carolina
South Carolina Clinical & Translational Research Institute (SCTR)
Investigators
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Principal Investigator: Colleen A Hanlon, PhD Medical University of South Carolina

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Responsible Party: Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT03576781     History of Changes
Other Study ID Numbers: 61328
First Posted: July 3, 2018    Key Record Dates
Last Update Posted: July 23, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No individual participant data will be shared. All data is deidentified.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Medical University of South Carolina:
Brain Stimulation
Treatment
Additional relevant MeSH terms:
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Opioid-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Chronic Pain
Pain
Neurologic Manifestations
Signs and Symptoms
Opiate Alkaloids
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents