NCT02969707

Use of Repetitive Transcranial Magnetic Stimulation to Augment Hypnotic Analgesia

Completed NA Results posted Last updated 20 December 2024

What this trial tests

NA trial testing MagPro TMS system (MagVenture, Denmark) in Fibromyalgia in 101 participants. Completed in 21 December 2019.

Timeline

24 April 2017

Primary endpoint
21 December 2019

21 December 2019

Quick facts

Lead sponsor	Stanford University
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	basic science
Enrollment	101
Start date	24 April 2017
Primary completion	21 December 2019
Estimated completion	21 December 2019
Sites	1 location across United States

Drugs / interventions tested

• MagPro TMS system (MagVenture, Denmark)
• Hypnosis

Conditions studied

• Fibromyalgia — all drugs for Fibromyalgia →

Sponsor

Stanford University

Who can join

Adults 18 to 70, any sex, with Fibromyalgia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

The Change in Functional Connectivity (FC) Between the Left Dorsolateral Prefrontal Cortex (L-DLPFC) and the Dorsal Anterior Cingulate Cortex (dACC) Primary · Baseline and at 15-20 min post-TMS (up to 30 min)

Functional MRI (fMRI) measures changes in oxygenated blood in the brain; at rest these levels fluctuate over time. These fluctuations can be similar between different brain regions. FC is the similarity in fluctuations of these fMRI signals and suggests how strongly two regions communicate with each other. We measured how inhibitory continuous theta-burst stimulation (cTBS) over L-DLPFC changes FC between L-DLPFC and dACC. This was done by estimating z-transformed correlation coefficients (CC) for each voxel (-1 to 1) between the L-DLPFC and dACC pre and post cTBS intervention. Negative FC was

Change in sum of positive z-transformed CC.

Group	Value	95% CI
Active rTMS	61.98	± 21.63
Sham rTMS	4.16	± 16.43

Change in sum of negative z-transformed CC.

Group	Value	95% CI
Active rTMS	-21.41	± 16.8
Sham rTMS	-13.22	± 16.8

Change in sum of all z-transformed CC.

Group	Value	95% CI
Active rTMS	40.56	± 32.34
Sham rTMS	-9.06	± 28.25

Change in Hypnotic Induction Profile Score Secondary · Baseline and Immediately post rTMS (up to 30 min)

The investigators used the Hypnotic Induction Profile (HIP) to determine the effect of active, inhibitory rTMS (cTBS) over L-DLPFC on enhancing hypnotizability. HIP scores range from 0 to 10 (low to high hypnotizability).

Group	Value	95% CI
Active rTMS	.63	± 1.18
Sham rTMS	.31	± 1.67

Change in The Hypnosis Intensity Scale Secondary · Baseline and immediately post rTMS (up to 2 hrs)

The investigators used the Hypnotic Intensity Scale (HIS) to determine the effect of active, inhibitory rTMS (cTBS) over L-DLPFC on enhancing hypnotic intensity. HIS scores range from 0 to 10 (low to high hypnotic intensity).

Group	Value	95% CI
Active rTMS	.475	± 2.242
Sham rTMS	-.128	± 1.490

The Change in Functional Connectivity (FC) Within The Neural Network Underlying Conflict Regulation. Secondary · Baseline and at 15-20 min post-TMS (up to 30 min)

We examined the effect of active, inhibitory cTBS over L-DLPFC on functional connectivity (FC) in key nodes in the neural network underlying the conflict regulation system. FC between each voxel in the L-DLPFC and the entire dACC was established by estimating z-transformed correlation coefficients (CC) for each voxel (-1 to 1) pre and post cTBS intervention. This paradigm was also used for voxels in the Default Mode Network (DMN) (Schaefer, 2018; Yeo, 2011) to the entire right inferior frontal gyrus (rIFG). Negative FC was assigned to voxels with a weight \< 0, positive FC to voxels with weigh

Change in sum of all z-transformed CC in L-DLPFC.

Group	Value	95% CI
Active rTMS	0.01	± 0.14
Sham rTMS	-0.003	± 0.13

Change in sum of positive z-transformed CC in L-DLPFC.

Group	Value	95% CI
Active rTMS	33.76	± 136.5
Sham rTMS	6.39	± 99.82

Change in sum of negative z-transformed CC in L-DLPFC.

Group	Value	95% CI
Active rTMS	-20.36	± 88.88
Sham rTMS	-10.11	± 96.55

Change in sum of all z-transformed CC in DMN.

Group	Value	95% CI
Active rTMS	0.004	± 0.05
Sham rTMS	-0.01	± 0.05

Change in sum of positive z-transformed CC in DMN.

Group	Value	95% CI
Active rTMS	-31.20	± 137.73
Sham rTMS	21.12	± 153.54

Change in sum of negative z-transformed CC in DMN.

Group	Value	95% CI
Active rTMS	51.35	± 243.68
Sham rTMS	-67.65	± 219.05

The Change in Stroop Performance Secondary · Baseline and at 15-20 min post-TMS (up to 30 min)

Stroop effect is measured by the response time of a participant during the stroop task. Increases in response time indicate increased stroop effect (SE) and vice versa.

Mean difference in change in Stroop effect (s) without hypnosis (TMS - no TMS) condition.

Group	Value	95% CI
Active rTMS	0.01	± 0.1
Sham rTMS	-0.02	± 0.082

Mean difference in change in Stroop effect (s) with hypnosis (TMS - no TMS) condition.

Group	Value	95% CI
Active rTMS	-0.04	± 0.12
Sham rTMS	-0.009	± .10

Stroop Task Secondary · Baseline and at 15-20 min post-TMS (up to 30 min)

Active, inhibitory cTBS effect over L-DLPFC on the neural network that underlies the hypnotic Stroop modulation effect was determined by first estimating the average of connectivity weights for all parcel pairs linking Ventral Attentional Network (VAN) to the DMN. Parcels are determined by extracting mean resting state BOLD time-series for each region of the Schaefer 100 parcellation. A correlation matrix between all parcels is created and FC weights for each pair are established by estimating z-transformed correlation coefficients (CC) (-1 to 1). Each parcel pair is then assigned to one of th

Group	Value	95% CI
Active rTMS	-0.026	± 0.0265
Sham rTMS	0.155	± 0.0297

Linear Relationship Between the Change in FC of the VAN to the DMN and the Change in Stroop Performance (Correlation Coefficient) With no Hypnosis Intervention. Secondary · Baseline and at 15-20 min post-TMS (up to 1 hr)

Spearman's correlation was used to determine the linear relationship between the response time taken to answer incongruent Stroop task blocks (a measure of Stroop performance) and the change the resting-state network FC between the VAN and the DMN when no hypnosis intervention was implemented.

Group	Value	95% CI
Active rTMS	0.18
Sham rTMS	-0.58

Linear Relationship Between the Change in FC of the VAN to the DMN and the Change in Stroop Performance (Correlation Coefficient) With Hypnosis Intervention. Secondary · Baseline and at 15-20 min post-TMS (up to 1 hr)

Spearman's correlation was used to determine the linear relationship between the response time taken to answer incongruent Stroop task blocks (a measure of Stroop performance) and the change the resting-state network FC between the VAN and the DMN when the hypnosis intervention was implemented.

Group	Value	95% CI
Active rTMS	0.16
Sham rTMS	0.16

Linear Relationship Between the Change in FC of the VAN to the DMN and the Change in Stroop Interference (Correlation Coefficient) With no Hypnosis Intervention. Secondary · Baseline and at 15-20 min post-TMS (up to 1 hr)

Spearman's correlation was used to determine the linear relationship between the Stroop interference and the change the resting-state network FC between the VAN and the DMN when no hypnosis intervention was implemented. In psychology, the Stroop effect is the delay in reaction time between congruent and incongruent stimuli.

Group	Value	95% CI
Active rTMS	0.24
Sham rTMS	-0.44

Linear Relationship Between the Change in FC of the VAN to the DMN and the Change in Stroop Interference (Correlation Coefficient) With Hypnosis Intervention. Secondary · Baseline and at 15-20 min post-TMS (up to 1 hr)

Spearman's correlation was used to determine the linear relationship between the Stroop interference and the change the resting-state network FC between the VAN and the DMN when the hypnosis intervention was implemented. In psychology, the Stroop effect is the delay in reaction time between congruent and incongruent stimuli.

Group	Value	95% CI
Active rTMS	0.07
Sham rTMS	0.28

Change in the Numeric Pain Rating Scale Secondary · Baseline and immediately post-rTMS (up to 30 minutes)

To determine the effect of active, inhibitory rTMS (cTBS) over L-DLPFC on modulating the neural network that underlies hypnotic analgesia (HA). Numeric Pain Rating Scale scores range from 0 to 10 (low to high pain intensity).

Non-hypnosis condition

Group	Value	95% CI
Active rTMS	-0.13	± 0.20
Sham rTMS	0.19	± 0.19

Hypnosis condition

Group	Value	95% CI
Active rTMS	-0.09	± 0.20
Sham rTMS	-0.05	± 0.19

Change in Sense of Agency Rating Scale (SOARS) Secondary · Baseline and immediately post-rTMS (up to 30 min)

The investigators used the Sense of Agency Rating Scale (SOARS) to determine the effect of active, inhibitory rTMS (cTBS) over L-DLPFC on altering the subjective sense of agency during hypnotizability. SOARS scores are calculated for Involuntariness and Effortlessness, each range from 0 to 35 (low to high).

Involuntariness

Group	Value	95% CI
Active rTMS	.3529	± 3.3654
Sham rTMS	1.1034	± 3.8391

Effortlessness

Group	Value	95% CI
Active rTMS	.8857	± 3.5378
Sham rTMS	.2727	± 3.1551

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 30 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Active rTMS

Serious: 0/49 (0%)

Deaths: 0/49

Sham rTMS

Serious: 0/52 (0%)

Deaths: 0/52

Other adverse events (3 terms — click to expand)

Reaction	System	Active rTMS	Sham rTMS
Medication Withdrawal During Washout	Metabolism and nutrition disorders	—	—
Headache / Scalp Irritation	Skin and subcutaneous tissue disorders	—	—
Dizziness	Ear and labyrinth disorders	—	—

Data from ClinicalTrials.gov NCT02969707 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. ACNP 60^th Annual Meeting: Poster Abstracts P1 - P275.
   · 2021 · cited 4× · PMID 34857904 · DOI 10.1038/s41386-021-01236-7
2. Modulation of a Stable Neurobehavioral Trait Using Repetitive Transcranial Magnetic Stimulation: A Preregistered Randomized Controlled Trial
   Faerman A, Bishop JH, Stimpson KH, Phillips A, et al · · 2021 · cited 3× · DOI 10.1101/2021.07.08.21260222