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Accelerated Theta Burst in Chronic Pain: A Biomarker Study

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ClinicalTrials.gov Identifier: NCT03984201
Recruitment Status : Not yet recruiting
First Posted : June 12, 2019
Last Update Posted : June 12, 2019
Sponsor:
Information provided by (Responsible Party):
Nolan R, Stanford University

Brief Summary:
This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for chronic pain. In this double blind, randomized control study, participants will be randomized to the treatment group to receive accelerated theta-burst stimulation or to a control group. All participants will be offered the open-label, active treatment 4 week prior to completing the initial 5 days of treatment.

Condition or disease Intervention/treatment Phase
Chronic Pain Device: Intermittent Theta Burst Stimulation (iTBS) Not Applicable

Detailed Description:
Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy for treatment-resistant depression and has been utilized to treat persons suffering from chronic pain. The approved method for treatment is 10Hz stimulation for 40 min over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been very successful in real world situations. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session). Recently, researchers have aggressively pursued modifying the treatment parameters to reduce treatment times with some preliminary success. This study intends to further modify the parameters to create a more rapid form of the treatment and look at the change in neuroimaging biomarkers.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Blinded, randomized control
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Accelerated Theta Burst in Chronic Pain: A Biomarker Study
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Chronic Pain

Arm Intervention/treatment
Active Comparator: iTBS over L-DLPFC to dACC

Participants will receive iTBS (intermittent theta burst stimulation) to the left dorsal lateral prefrontal cortex (L-DLPFC) with high connectivity to the dorsal anterior cingulate cortex (dACC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold adjust to the skull to cortical surface distance.

Stimulation will be delivered to L-DLPFC using the MagPRo stimulator.

Device: Intermittent Theta Burst Stimulation (iTBS)
Participants will receive active or sham transcranial magnetic stimulation delivered to the L-DLPFC.
Other Names:
  • Accelerated Theta Burst Stimulation (aTBS)
  • Repetitive Transcranial Magnetic Stimulation (rTMS)

Active Comparator: iTBS over L-DLPFC to sgACC

Participants will receive iTBS (intermittent theta burst stimulation) to the left dorsal lateral prefrontal cortex (L-DLPFC) with high connectivity to the subgenual cingulate cortex (sgACC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold adjust to the skull to cortical surface distance.

Stimulation will be delivered to L-DLPFC using the MagPRo stimulator.

Device: Intermittent Theta Burst Stimulation (iTBS)
Participants will receive active or sham transcranial magnetic stimulation delivered to the L-DLPFC.
Other Names:
  • Accelerated Theta Burst Stimulation (aTBS)
  • Repetitive Transcranial Magnetic Stimulation (rTMS)

Sham Comparator: Sham iTBS over L-DLPFC

Participants will receive sham iTBS (intermittent theta burst stimulation) to the left DLPFC. The L-DLPFC will be targeted utilizing the Localite neuronavigation system.

Sham stimulation will be delivered to L-DLPFC using the MagPRo stimulator.

Device: Intermittent Theta Burst Stimulation (iTBS)
Participants will receive active or sham transcranial magnetic stimulation delivered to the L-DLPFC.
Other Names:
  • Accelerated Theta Burst Stimulation (aTBS)
  • Repetitive Transcranial Magnetic Stimulation (rTMS)




Primary Outcome Measures :
  1. Change in the Brief Pain Inventory (BPI) score [ Time Frame: Pre-treatment, immediately post-treatment ]

    A self-report measure designed to enable investigators to easily obtain sensitive measures of the degree of depression and individual is experiencing.

    Scoring:

    1. Pain Severity Score: This is calculated by adding the scores for questions 2, 3, 4 and 5 and then dividing by 4. This gives a severity score out of 10.
    2. Pain Interference Score: This is calculated by adding the scores for questions 8a, b, c, d, e, f and g and then dividing by 7. This gives an interference score out of 10.

  2. Change in the McGill Pain Questionnaire score [ Time Frame: Pre-treatment, immediately post-treatment ]
    A self-report questionnaire that allows individuals that assesses the quality and intensity of pain that is experienced. The pain rating index has 2 subscales: sensory subscale with 11 words, and affective subscale with 4 words. These items are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate and 3 = severe. There's also one item for present pain intensity and one item for a 10cm visual analogue scale for average pain.


Secondary Outcome Measures :
  1. Change in the Montgomery Asberg Depression Rating Scale (MADRS) score [ Time Frame: Pre-treatment, immediately post-treatment, 2 weeks post-treatment, 4 weeks post-treatment ]

    A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders.

    Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60; 0 to 6 - normal, symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; >34 - severe depression.


  2. Change in teh Hamilton Rating Scale for Depression (HAM-17) score [ Time Frame: Pre-treatment, immediately post-treatment, 2 weeks post-treatment, 4 weeks post-treatment ]
    A provider administered questionnaire used to assess remission and recovery from depression. in general the higher the total score the more severe the depression. HAM-D score level of depression: 10-13 mild; 14-17 mild to moderate; >17 moderate to severe.

  3. Change in the Pain Catastrophizing Scale (PCS) score [ Time Frame: Pre-treatment, immediately post-treatment, 2 weeks post-treatment, 4 weeks post-treatment ]
    A self-report measure, consisting of 13 items scored from 0 to 4, resulting in a total possible score of 52 that measures a person's catastrophizing of pain. A higher score indicates a higher level of pain catastrophizing.

  4. Change in functional connectivity as measured by Functional Magnetic Resonance Imaging (fMRI) [ Time Frame: Pre-treatment, immediately post-treatment, 4 weeks post-treatment ]
    Participants will have fMRI scans both before the first treatment (baseline) and after the aiTBS course. The MRI scans will be used to identify potential biomarkers for antidepressant response and pain response, as well as identify aiTBS-induced changes in functional connectivity.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients need to meet at least a 4/10 on a clinical pain rating scale and/or fulfill fibromyalgia diagnostic criteria on the 2010 Fibromyalgia Diagnostic Criteria (Wolfe et al., 2010)
  2. Age 18 - 70
  3. Right-handed
  4. Agree to having fMRI scans as well as rTMS sessions
  5. Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and treatment
  6. Women of childbearing potential must agree to use adequate contraception prior to study entry and continue this for the duration of the study
  7. Participants may continue antidepressant regimen, but must be stable for 6 weeks prior to enrollment in the study. Antidepressant must be of the SSRI class only (if currently on a different antidepressant, patients will be switched to an SSRI). They must maintain that same antidepressant regimen throughout the study duration.

Exclusion Criteria:

  1. History of MI, CABG, CHF, or other cardiac history.
  2. Any condition that would contraindicate MRI (such as ferromagnetic metal in the body)
  3. Pregnancy or breastfeeding
  4. Any neurological condition, history of epilepsy, history of rTMS failure with FDA approved rTMS parameters, history of any implanted device or psychosurgery for depression, history of receiving ECT. OCD, narcolepsy or any additional significant neurological disorder as determined by the PI.
  5. Autism spectrum disorder
  6. Inability to stop taking medication contraindicated with treatment
  7. Any significant psychiatric disorder as identified on the Mini International Neuropsychiatric Interview and determined by the PI
  8. A positive urine toxicology screen

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): NCT03984201


Contacts
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Contact: Katy Stimpson, BS 650-736-2233 kstimpson@stanford.edu
Contact: James Bishop, PhD 650-736-2233 jhbishop@stanford.edu

Locations
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United States, California
Stanford University Not yet recruiting
Palo Alto, California, United States, 94304
Contact: Katy Stimpson    650-736-2233    kstimpson@stanford.edu   
Contact: James Bishop, PhD    650-736-2233    jhbishop@stanford.edu   
Sponsors and Collaborators
Stanford University

Publications:
Ochsner, K. N., & Gross, J. J. (2005). Putting the ' I ' and the ' Me ' in emotion regulation : Reply to Northoff, (xx), 6613. https://doi.org/10.1016/j.tics.2005.06.005

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Responsible Party: Nolan R, Assistant Professor of Psychiatry and Behavioral Sciences, Stanford University
ClinicalTrials.gov Identifier: NCT03984201     History of Changes
Other Study ID Numbers: 48366
First Posted: June 12, 2019    Key Record Dates
Last Update Posted: June 12, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Nolan R, Stanford University:
Chronic Pain
Repetitive Transcranial Magnetic Stimulation (rTMS)
Accelerated Theta Burst Stimulation (aTBS)
Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT)

Additional relevant MeSH terms:
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Chronic Pain
Pain
Neurologic Manifestations
Signs and Symptoms