Use of Repetitive Transcranial Magnetic Stimulation to Augment Hypnotic Analgesia

Use of Repetitive Transcranial Magnetic Stimulation to Augment Hypnotic Analgesia

Sponsors

Lead Sponsor: Stanford University

Collaborator: National Institutes of Health (NIH)
National Center for Complementary and Integrative Health (NCCIH)

Source Stanford University
Brief Summary

The investigators plan to use functional neuroimaging (fMRI) to understand the brain systems affected when hypnosis and hypnotic analgesia are augmented with repetitive transcranial magnetic stimulation (rTMS), a form of non-invasive brain stimulation to 100 people with fibromyalgia, a chronic pain condition. The investigators will measure the effect of rTMS-augmentation on the brain networks underlying hypnotizability, as well as the effect of rTMS-augmentation on hypnotic analgesia networks. The investigators hope to demonstrate that a combination of these psychological and neuromodulatory treatments will be more effective than hypnosis alone, thereby enhancing the depth of hypnosis, range of hypnosis and the efficacy of hypnotic analgesia and hopefully creating a new treatment modality for individuals suffering from pain syndromes such as fibromyalgia pain.

Detailed Description

Overall Study Design. The investigators propose to develop a combinatory approach where an integrative technique (hypnosis) is augmented with a neurotechnology (repetitive transcranial magnetic stimulation). This application seeks to utilize the previously established brain-based mechanisms of both hypnosis and repetitive transcranial magnetic stimulation as biomarkers to assess the potential synergistic mechanism of this combinatory approach. 100 low-moderately hypnotizable subjects with fibromyalgia will be identified. The subjects' response to rTMS-augmentation of hypnosis will be measured. The volunteers will be randomized to active or sham rTMS. Two scan sessions will be performed for each subject, with the first scan session investigating the effect of rTMS-augmentation on hypnosis and hypnotizability (120 min scan session) and the second scan session focused on the effect of rTMS-augmented hypnotic analgesia (120 min scan session). The study will require that participants participate in an in-person screening visit, a screening MRI scan and 2 MRI scan sessions that include the TMS and hypnosis. Experimental design. Before each MRI scan session, participants will undergo a preparation session, where hypnotizability and either psychological testing or experimental pain training will be conducted. Volunteer subjects will then participate in 2 MRI scan sessions on two separate days, each lasting approximately 120 mins. Hypnosis induction procedures. Hypnosis will be induced while the subject is in the scanner though the use of headphones and a pre-recorded induction script. Hypnotic instructions will be standardized, and will involve a simple induction instruction used in our prior research on the brain signature of the hypnotic state and in clinical care. The ability to enter and maintain the hypnotic state through such an induction mechanism in the fMRI environment has been previously demonstrated.

Overall Status Completed
Start Date April 24, 2017
Completion Date December 21, 2019
Primary Completion Date December 21, 2019
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
The change in functional connectivity between the L-DLPFC and the dACC Baseline, post-TMS and during hypnotic induction
Secondary Outcome
Measure Time Frame
The change in the neural network underlying hypnotic intensity Baseline and 2 hours
Hypnotic Induction Profile Baseline and 2 hours
The Hypnosis Intensity Scale Baseline and 2 hours
The change in the neural network underlying the conflict regulation system Baseline and 2 hours
Stroop task Baseline and 2 hours
The Numeric Pain Rating Scale Baseline and 2 hours
Sense of Agency Rating Scale (SOARS) Baseline and 2 hours
Metabolic alterations in fibromyalgia Baseline
Metabolic changes in hypnotic analgesia pre- and post-rTMS Baseline and 2 hours
Enrollment 100
Condition
Intervention

Intervention Type: Device

Intervention Name: repetitive Transcranial Magnetic Stimulation

Description: The investigators will perform two applications of 40s of continuous theta-burst stimulation (cTBS) form of rTMS at 80% resting motor threshold (previously determined), with a 15 minute intersession interval. The standardized treatment location for the left DLPFC will be determined by Localite Neuronavigation and targeted at the posterior middle frontal gyrus. The baseline structural scan obtained during the scan 1 will be utilized for this localization process. rTMS will be delivered using a MagPro TMS system (MagVenture, Denmark).

Arm Group Label: Active rTMS

Other Name: rTMS

Intervention Type: Device

Intervention Name: Sham repetitive Transcranial Magnetic Stimulation

Description: This will be identical to active rTMS except the stimulation will be blocked. Both active and sham repetitive Transcranial Magnetic Stimulation will receive simulation from a specially designed coil which is capable of delivering either active rTMS or sham rTMS in a manner, which is randomized by the system itself and therefore blinded to the treater. rTMS will be delivered using a MagPro TMS system (MagVenture, Denmark).

Arm Group Label: Sham rTMS

Other Name: sham rTMS

Eligibility

Criteria:

Inclusion Criteria: - Fulfill 2010 Fibromyalgia Diagnostic Criteria - Age 18 - 70 - Right-handed - Agree to and able to have two fMRI scans as well as rTMS sessions - Willingness to suspend use of analgesic drugs or cough suppressants for 24 hours prior to the scans - Willingness to suspend us of antidepressant drugs for 2 weeks prior to the scans (6 weeks for fluoxetine) - Proficiency in English sufficient to complete questionnaires/follow instructions during fMRI assessments - US Citizen or resident able to receive payment legally - Low-Moderate Hypnotizability in the Hypnotic Induction Profile (score of 0-8) - Normal color vision - Women of childbearing potential must agree to use adequate contraception prior to study entry and continue this for the duration of the study Exclusion Criteria: - A medical condition that would contraindicate the use of rTMS - Any condition that would contraindicate MRI (like ferromagnetic metal in the body) - Pregnancy or breast feeding - Any significant neurologic disease, including dementia, multi-infarct dementia, Parkinson's or Huntington's disease, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, history of significant head trauma - Current antidepressant use (must be washed out for two weeks prior to starting protocol) - Inability to stop taking medication contraindicated with treatment - High Hypnotizability in the Hypnotic Induction Profile (score >8) - Any significant psychiatric disorder as identified on the Mini Mental State Exam (Dysthymia not an exclusion criteria) - Color blindness - Any significant psychiatric disorder as identified on the Mini International Neuropsychiatric Interview - Previous exposure to rTMS

Gender: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Nolan Williams, M.D. Principal Investigator Stanford University
Location
Facility: Stanford University
Location Countries

United States

Verification Date

January 2021

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Stanford University

Investigator Full Name: David Spiegel

Investigator Title: Willson Professor and Associate Chair of Psychiatry & Behavioral Sciences, Director of the Center on Stress and Health, and Medical Director of the Center for Integrative Medicine at Stanford University School of Medicine

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Active rTMS

Type: Experimental

Description: The active group will receive repetitive Transcranial Magnetic Stimulation

Label: Sham rTMS

Type: Sham Comparator

Description: The sham repetitive Transcranial Magnetic Stimulation group will have the stimulation blocked.

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Basic Science

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov