Accelerated Theta Burst in Chronic Pain: A Biomarker Study

Chronic Pain Clinical Trial

Official title:

Accelerated Theta Burst in Chronic Pain: A Biomarker Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03984201
• Other study ID #: 48366
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2023
• Est. completion date: August 2025

Study information

• Verified date: May 2022
• Source: Stanford University
• Contact: Katy Stimpson, BS
• Phone: 650-736-2233
• Email: kstimpson[@]stanford.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: August 2025
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Pain

Intervention

Device:
• Intermittent Theta Burst Stimulation (iTBS)
Participants will receive active or sham transcranial magnetic stimulation delivered to the L-DLPFC.

Locations

Country	Name	City	State
United States	Stanford University	Palo Alto	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (31)

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George MS, Taylor JJ, Short EB. The expanding evidence base for rTMS treatment of depression. Curr Opin Psychiatry. 2013 Jan;26(1):13-8. doi: 10.1097/YCO.0b013e32835ab46d. Review. — View Citation

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Lan MJ, Chhetry BT, Liston C, Mann JJ, Dubin M. Transcranial Magnetic Stimulation of Left Dorsolateral Prefrontal Cortex Induces Brain Morphological Changes in Regions Associated with a Treatment Resistant Major Depressive Episode: An Exploratory Analysis. Brain Stimul. 2016 Jul-Aug;9(4):577-83. doi: 10.1016/j.brs.2016.02.011. Epub 2016 Mar 2. — View Citation

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Lee SJ, Kim DY, Chun MH, Kim YG. The effect of repetitive transcranial magnetic stimulation on fibromyalgia: a randomized sham-controlled trial with 1-mo follow-up. Am J Phys Med Rehabil. 2012 Dec;91(12):1077-85. doi: 10.1097/PHM.0b013e3182745a04. — View Citation

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Li CT, Chen MH, Juan CH, Huang HH, Chen LF, Hsieh JC, Tu PC, Bai YM, Tsai SJ, Lee YC, Su TP. Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study. Brain. 2014 Jul;137(Pt 7):2088-98. doi: 10.1093/brain/awu109. Epub 2014 May 10. — View Citation

Oberman L, Edwards D, Eldaief M, Pascual-Leone A. Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. J Clin Neurophysiol. 2011 Feb;28(1):67-74. doi: 10.1097/WNP.0b013e318205135f. Review. — View Citation

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Vanneste S, Ost J, Langguth B, De Ridder D. TMS by double-cone coil prefrontal stimulation for medication resistant chronic depression: a case report. Neurocase. 2014;20(1):61-8. doi: 10.1080/13554794.2012.732086. Epub 2012 Oct 11. — View Citation

Williams NR, Sudheimer KD, Bentzley BS, Pannu J, Stimpson KH, Duvio D, Cherian K, Hawkins J, Scherrer KH, Vyssoki B, DeSouza D, Raj KS, Keller J, Schatzberg AF. High-dose spaced theta-burst TMS as a rapid-acting antidepressant in highly refractory depression. Brain. 2018 Mar 1;141(3):e18. doi: 10.1093/brain/awx379. — View Citation

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* Note: There are 31 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the Brief Pain Inventory (BPI) score	A self-report measure designed to enable investigators to easily obtain sensitive measures of the degree of depression and individual is experiencing.; Scoring: 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.; 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
Primary	Change in the McGill Pain Questionnaire score	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	Change in the Montgomery Asberg Depression Rating Scale (MADRS) score	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
Secondary	Change in teh Hamilton Rating Scale for Depression (HAM-17) score	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
Secondary	Change in the Pain Catastrophizing Scale (PCS) score	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
Secondary	Change in functional connectivity as measured by Functional Magnetic Resonance Imaging (fMRI)	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