Accelerated Theta Burst in Chronic Pain: A Biomarker Study

May 4, 2022 updated by: Nolan R, Stanford University
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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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:
  • Repetitive Transcranial Magnetic Stimulation (rTMS)
  • Accelerated Theta Burst Stimulation (aTBS)
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:
  • Repetitive Transcranial Magnetic Stimulation (rTMS)
  • Accelerated Theta Burst Stimulation (aTBS)
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:
  • Repetitive Transcranial Magnetic Stimulation (rTMS)
  • Accelerated Theta Burst Stimulation (aTBS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Pre-treatment, immediately post-treatment
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.
Pre-treatment, immediately post-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Pre-treatment, immediately post-treatment, 2 weeks post-treatment, 4 weeks post-treatment
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.
Pre-treatment, immediately post-treatment, 2 weeks post-treatment, 4 weeks post-treatment
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.
Pre-treatment, immediately post-treatment, 2 weeks post-treatment, 4 weeks post-treatment
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.
Pre-treatment, immediately post-treatment, 4 weeks post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 1, 2023

Primary Completion (Anticipated)

August 1, 2024

Study Completion (Anticipated)

August 1, 2025

Study Registration Dates

First Submitted

May 30, 2019

First Submitted That Met QC Criteria

June 11, 2019

First Posted (Actual)

June 12, 2019

Study Record Updates

Last Update Posted (Actual)

May 6, 2022

Last Update Submitted That Met QC Criteria

May 4, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 48366

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Chronic Pain

Clinical Trials on Intermittent Theta Burst Stimulation (iTBS)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Greece

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe