Trial Outcomes & Findings for Feasibility Study: fMRI Evaluation of Auricular PENFS for Fibromyalgia (NCT NCT03008837)
NCT ID: NCT03008837
Last Updated: 2020-07-27
Results Overview
2 weeks following the final treatment, subjects in the PENFS group were be evaluated for changes in functional connectivity between the right posterior insula seed and other areas of the DMN as evaluated by fcMRI relative to standard treatment controls, using whole brain analysis. The measurement is increase/decrease of signal in a given region, thresholded at p \<0.05, summarized into a value representing 'size of region of increase' or 'size of region of decrease' after subjects scans were combined/mapped onto a standard MNI brain. Only clusters of over 40 voxels were included, and the size of the region is reported in voxel size. The averaged brains for baseline fcMRI was subtracted from post-treatment for each group, and then these averaged differences were subtracted from each other. While other areas of the brain met threshold criteria in the analysis, only areas belonging to the DMN are reported.
COMPLETED
NA
27 participants
baseline and 2 weeks post-treatment
2020-07-27
Participant Flow
27 veterans were initially consented. However, 6 of these veterans either could not begin the study within the study period, moved out of state, or received implanted MRI-incompatible devices that excluded them from the study following the initial consent, but prior to randomization.
Participant milestones
| Measure |
PENFS
Veterans with fibromyalgia who meet study criteria and are randomized to the experimental group will receive standard therapy in addition to percutaneous electrical neural field stimulation (PENFS), which involves placement of small electrodes through a similar process to ear acupuncture to the ear. These electrodes are attached to a battery pack that is taped behind the ear and worn for 5-day intervals. The intention of this FDA-approved device is to relieve pain, though data on its effectiveness is still limited. Device placement (series of 4, weekly) will be performed by an Anesthesiology Pain Clinic provider. fMRI evaluation of neural changes, assessment of function and quality of life improvements will be performed at the beginning and end of the study.
Military Field Stimulator: The Military Field Stimulator (MFS/Neuro-Stim System), a percutaneous electrical neural field stimulation (PENFS) device evolved from PENS, is currently employed by the United States (US) military
|
Standard Therapy
Veterans with fibromyalgia who meet study criteria and are randomized to standard therapy will receive physical therapy, medication management through the Anesthesiology Pain Clinic, and referral to a pain psychologist. fMRI evaluation of neural changes, assessment of function and quality of life improvements will be performed at the beginning and end of the study.
Standard Therapy: Standard therapy for fibromyalgia will include physical therapy, medication management through the Anesthesiology Pain Clinic, and referral to a pain psychologist.
|
|---|---|---|
|
Overall Study
STARTED
|
12
|
9
|
|
Overall Study
COMPLETED
|
9
|
5
|
|
Overall Study
NOT COMPLETED
|
3
|
4
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Feasibility Study: fMRI Evaluation of Auricular PENFS for Fibromyalgia
Baseline characteristics by cohort
| Measure |
PENFS
n=12 Participants
Veterans with fibromyalgia who meet study criteria and are randomized to the experimental group will receive standard therapy in addition to percutaneous electrical neural field stimulation (PENFS), which involves placement of small electrodes through a similar process to ear acupuncture to the ear. These electrodes are attached to a battery pack that is taped behind the ear and worn for 5-day intervals. The intention of this FDA-approved device is to relieve pain, though data on its effectiveness is still limited. Device placement (series of 4, weekly) will be performed by an Anesthesiology Pain Clinic provider. fMRI evaluation of neural changes, assessment of function and quality of life improvements will be performed at the beginning and end of the study.
|
Standard Therapy
n=9 Participants
Veterans with fibromyalgia who meet study criteria and are randomized to standard therapy will receive physical therapy, medication management through the Anesthesiology Pain Clinic, and referral to a pain psychologist. fMRI evaluation of neural changes, assessment of function and quality of life improvements will be performed at the beginning and end of the study.
Standard Therapy: Standard therapy for fibromyalgia will include physical therapy, medication management through the Anesthesiology Pain Clinic, and referral to a pain psychologist.
|
Total
n=21 Participants
Total of all reporting groups
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|---|---|---|---|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Age, Continuous
|
50 years
n=5 Participants
|
48.56 years
n=7 Participants
|
49.35 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
12 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
DVPRS (Pain)
|
6.42 units on a scale
STANDARD_DEVIATION 0.84 • n=5 Participants
|
8 units on a scale
STANDARD_DEVIATION 0.77 • n=7 Participants
|
7.41 units on a scale
STANDARD_DEVIATION 1.35 • n=5 Participants
|
PRIMARY outcome
Timeframe: baseline and 2 weeks post-treatmentPopulation: Using a right posterior insula seed for seed-based whole-brain analysis in AFNI, a difference of the differences was measured. Clusters greater than 40 voxels in size with p\<0.05 (set in AFNI) found in the default mode network (DMN) are included in the outcome table.
2 weeks following the final treatment, subjects in the PENFS group were be evaluated for changes in functional connectivity between the right posterior insula seed and other areas of the DMN as evaluated by fcMRI relative to standard treatment controls, using whole brain analysis. The measurement is increase/decrease of signal in a given region, thresholded at p \<0.05, summarized into a value representing 'size of region of increase' or 'size of region of decrease' after subjects scans were combined/mapped onto a standard MNI brain. Only clusters of over 40 voxels were included, and the size of the region is reported in voxel size. The averaged brains for baseline fcMRI was subtracted from post-treatment for each group, and then these averaged differences were subtracted from each other. While other areas of the brain met threshold criteria in the analysis, only areas belonging to the DMN are reported.
Outcome measures
| Measure |
PENFS (Post-pre)
n=9 Participants
Veterans with fibromyalgia who meet study criteria and are randomized to the experimental group will receive standard therapy in addition to percutaneous electrical neural field stimulation (PENFS). This column shows the number of voxels in clusters that showed increased or decreased connectivity following treatment, \>40 voxel clusters, thresholded at p\<0.05 in AFNI.
|
Standard Therapy Control (Post-pre)
n=7 Participants
Veterans with fibromyalgia who meet study criteria and are randomized to the control group will receive standard therapy including medications and physical therapy. This column shows the number of voxels in clusters that showed increased or decreased connectivity following standard therapy, \>40 voxel clusters, thresholded at p\<0.05 in AFNI.
|
|---|---|---|
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fcMRI as a Biomarker to Investigate Functionally Correlated Neural Substrates of Pain in Patients Undergoing PENFS
Anterior cingulate (L)
|
0 Cluster size (voxels)
|
0 Cluster size (voxels)
|
|
fcMRI as a Biomarker to Investigate Functionally Correlated Neural Substrates of Pain in Patients Undergoing PENFS
Inferior parietal lobule (R)
|
0 Cluster size (voxels)
|
0 Cluster size (voxels)
|
|
fcMRI as a Biomarker to Investigate Functionally Correlated Neural Substrates of Pain in Patients Undergoing PENFS
Posterior cingulate cortex (L)
|
0 Cluster size (voxels)
|
61 Cluster size (voxels)
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SECONDARY outcome
Timeframe: 2, 6 and 12 weeks follow-upPopulation: Not all individuals presented for all follow-up visits, but all participants included in the analysis were present for baseline assessments, pre- and post- imaging studies, and at least one follow-up visit. Missing data was not imputed and not used for analysis in order to avoid distortions related to imputation in the small sample size.
For fibromyalgia patients, pain will be assessed in the PENFS group relative to standard treatment controls, as indicated by analgesic Defense and Veterans Pain Rating Scale (DVPRS) at 2, 6 and 12 weeks follow-up. This is a validated pain measure that includes a 0-10 scale where 0 means no pain and 10 means greatest pain imaginable. Higher scores indicate worse reported pain outcomes.
Outcome measures
| Measure |
PENFS (Post-pre)
n=9 Participants
Veterans with fibromyalgia who meet study criteria and are randomized to the experimental group will receive standard therapy in addition to percutaneous electrical neural field stimulation (PENFS). This column shows the number of voxels in clusters that showed increased or decreased connectivity following treatment, \>40 voxel clusters, thresholded at p\<0.05 in AFNI.
|
Standard Therapy Control (Post-pre)
n=7 Participants
Veterans with fibromyalgia who meet study criteria and are randomized to the control group will receive standard therapy including medications and physical therapy. This column shows the number of voxels in clusters that showed increased or decreased connectivity following standard therapy, \>40 voxel clusters, thresholded at p\<0.05 in AFNI.
|
|---|---|---|
|
Change in Defense Veterans Pain Rating Scale (DVPRS) From Baseline
2 weeks
|
-0.9 score on a scale
Interval -4.4 to 2.6
|
-1.4 score on a scale
Interval -8.8 to 6.0
|
|
Change in Defense Veterans Pain Rating Scale (DVPRS) From Baseline
6 weeks
|
-1.1 score on a scale
Interval -5.1 to 2.9
|
-0.5 score on a scale
Interval -2.6 to 1.6
|
|
Change in Defense Veterans Pain Rating Scale (DVPRS) From Baseline
12 weeks
|
-1.3 score on a scale
Interval -5.3 to 2.7
|
-0.1 score on a scale
Interval -3.4 to 3.2
|
SECONDARY outcome
Timeframe: 2, 6 and 12 weeks follow-upPopulation: Not all individuals presented for all follow-up visits, but all participants included in the analysis were present for baseline assessments, pre- and post- imaging studies, and at least one follow-up visit. Missing data was not imputed and not used for analysis in order to avoid distortions related to imputation in the small sample size.
Pain interference scores were measured using supplemental questions on the Defense and Veterans Pain Rating Scale (DVPRS). Participants were asked to evaluate on a scale of 0-10 the level to which pain interfered with their "activity," "sleep," "mood", and "stress," with 10 being the worst interference, and 0 being no interference.
Outcome measures
| Measure |
PENFS (Post-pre)
n=9 Participants
Veterans with fibromyalgia who meet study criteria and are randomized to the experimental group will receive standard therapy in addition to percutaneous electrical neural field stimulation (PENFS). This column shows the number of voxels in clusters that showed increased or decreased connectivity following treatment, \>40 voxel clusters, thresholded at p\<0.05 in AFNI.
|
Standard Therapy Control (Post-pre)
n=7 Participants
Veterans with fibromyalgia who meet study criteria and are randomized to the control group will receive standard therapy including medications and physical therapy. This column shows the number of voxels in clusters that showed increased or decreased connectivity following standard therapy, \>40 voxel clusters, thresholded at p\<0.05 in AFNI.
|
|---|---|---|
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Change in Pain Interference With "Activity," "Sleep," "Mood", and "Stress" From Baseline
2 weeks - Activity
|
-1.2 score on a scale
Interval -4.7 to 2.3
|
0.9 score on a scale
Interval -8.0 to 9.8
|
|
Change in Pain Interference With "Activity," "Sleep," "Mood", and "Stress" From Baseline
2 weeks - Sleep
|
-1.6 score on a scale
Interval -7.4 to 4.2
|
-0.4 score on a scale
Interval -11.7 to 10.9
|
|
Change in Pain Interference With "Activity," "Sleep," "Mood", and "Stress" From Baseline
2 weeks - Mood
|
-1 score on a scale
Interval -6.1 to 4.1
|
-0.6 score on a scale
Interval -11.1 to 9.9
|
|
Change in Pain Interference With "Activity," "Sleep," "Mood", and "Stress" From Baseline
2 weeks - Stress
|
-1.4 score on a scale
Interval -5.0 to 2.2
|
0 score on a scale
Interval -9.7 to 9.7
|
|
Change in Pain Interference With "Activity," "Sleep," "Mood", and "Stress" From Baseline
6 weeks - Activity
|
-1.2 score on a scale
Interval -5.7 to 3.3
|
1.2 score on a scale
Interval -1.9 to 4.3
|
|
Change in Pain Interference With "Activity," "Sleep," "Mood", and "Stress" From Baseline
6 weeks - Sleep
|
-1.6 score on a scale
Interval -7.1 to 3.9
|
1.8 score on a scale
Interval -2.4 to 6.0
|
|
Change in Pain Interference With "Activity," "Sleep," "Mood", and "Stress" From Baseline
6 weeks - Mood
|
-1.4 score on a scale
Interval -6.7 to 3.9
|
1.8 score on a scale
Interval -2.7 to 6.3
|
|
Change in Pain Interference With "Activity," "Sleep," "Mood", and "Stress" From Baseline
6 weeks - Stress
|
-1.8 score on a scale
Interval -6.2 to 2.6
|
1.7 score on a scale
Interval -1.9 to 5.3
|
|
Change in Pain Interference With "Activity," "Sleep," "Mood", and "Stress" From Baseline
12 weeks - Activity
|
-1.6 score on a scale
Interval -6.3 to 3.1
|
1 score on a scale
Interval -6.2 to 8.2
|
|
Change in Pain Interference With "Activity," "Sleep," "Mood", and "Stress" From Baseline
12 weeks - Sleep
|
-1.7 score on a scale
Interval -6.3 to 2.9
|
2.2 score on a scale
Interval -3.7 to 8.1
|
|
Change in Pain Interference With "Activity," "Sleep," "Mood", and "Stress" From Baseline
12 weeks - Mood
|
-2.1 score on a scale
Interval -6.4 to 2.2
|
1.8 score on a scale
Interval -5.5 to 9.1
|
|
Change in Pain Interference With "Activity," "Sleep," "Mood", and "Stress" From Baseline
12 weeks - Stress
|
-1.9 score on a scale
Interval -5.2 to 1.4
|
1.8 score on a scale
Interval -4.6 to 8.2
|
SECONDARY outcome
Timeframe: 2, 6 and 12 weeks follow-upPopulation: Not all individuals presented for all follow-up visits, but all participants included in the analysis were present for baseline assessments, pre- and post- imaging studies, and at least one follow-up visit. Missing data was not imputed and not used for analysis in order to avoid distortions related to imputation in the small sample size.
Objective tests for functional improvement will be performed at 2, 6, and 12 weeks follow-up and include 30 sec chair stand tests. The total number of full bicep curls (left arm) participants could perform using were measured over a 30-second period at each visit.
Outcome measures
| Measure |
PENFS (Post-pre)
n=9 Participants
Veterans with fibromyalgia who meet study criteria and are randomized to the experimental group will receive standard therapy in addition to percutaneous electrical neural field stimulation (PENFS). This column shows the number of voxels in clusters that showed increased or decreased connectivity following treatment, \>40 voxel clusters, thresholded at p\<0.05 in AFNI.
|
Standard Therapy Control (Post-pre)
n=7 Participants
Veterans with fibromyalgia who meet study criteria and are randomized to the control group will receive standard therapy including medications and physical therapy. This column shows the number of voxels in clusters that showed increased or decreased connectivity following standard therapy, \>40 voxel clusters, thresholded at p\<0.05 in AFNI.
|
|---|---|---|
|
Change in Number of Bicep Curls From Baseline (Left Arm)
2 weeks
|
4.6 bicep curls
Interval -8.1 to 17.3
|
1.7 bicep curls
Interval -12.0 to 15.4
|
|
Change in Number of Bicep Curls From Baseline (Left Arm)
6 weeks
|
6.1 bicep curls
Interval -7.0 to 19.2
|
-1.8 bicep curls
Interval -14.2 to 10.6
|
|
Change in Number of Bicep Curls From Baseline (Left Arm)
12 weeks
|
5.8 bicep curls
Interval -7.4 to 19.0
|
0 bicep curls
Interval -15.5 to 15.5
|
SECONDARY outcome
Timeframe: 2, 6 and 12 weeks follow-upPopulation: Not all individuals presented for all follow-up visits, but all participants included in the analysis were present for baseline assessments, pre- and post- imaging studies, and at least one follow-up visit. Missing data was not imputed and not used for analysis in order to avoid distortions related to imputation in the small sample size.
Objective tests for functional improvement will be performed at 2, 6, and 12 weeks follow-up and include 30 sec chair stand tests. The total number of full bicep curls (right arm) participants could perform using were measured over a 30-second period at each visit.
Outcome measures
| Measure |
PENFS (Post-pre)
n=9 Participants
Veterans with fibromyalgia who meet study criteria and are randomized to the experimental group will receive standard therapy in addition to percutaneous electrical neural field stimulation (PENFS). This column shows the number of voxels in clusters that showed increased or decreased connectivity following treatment, \>40 voxel clusters, thresholded at p\<0.05 in AFNI.
|
Standard Therapy Control (Post-pre)
n=7 Participants
Veterans with fibromyalgia who meet study criteria and are randomized to the control group will receive standard therapy including medications and physical therapy. This column shows the number of voxels in clusters that showed increased or decreased connectivity following standard therapy, \>40 voxel clusters, thresholded at p\<0.05 in AFNI.
|
|---|---|---|
|
Change in Number of Bicep Curls From Baseline (Right Arm)
2 weeks
|
4.2 bicep curls
Interval -5.8 to 14.2
|
0.7 bicep curls
Interval -14.4 to 15.8
|
|
Change in Number of Bicep Curls From Baseline (Right Arm)
6 weeks
|
6 bicep curls
Interval -8.4 to 20.4
|
0.8 bicep curls
Interval -12.4 to 14.0
|
|
Change in Number of Bicep Curls From Baseline (Right Arm)
12 weeks
|
4.6 bicep curls
Interval -8.7 to 17.9
|
0.2 bicep curls
Interval -11.2 to 11.6
|
SECONDARY outcome
Timeframe: 2, 6 and 12 weeks follow-upPopulation: Not all individuals presented for all follow-up visits, but all participants included in the analysis were present for baseline assessments, pre- and post- imaging studies, and at least one follow-up visit. Missing data was not imputed and not used for analysis in order to avoid distortions related to imputation in the small sample size.
Objective tests for functional improvement will be performed at 2, 6, and 12 weeks follow-up and include 30 sec chair stand tests. The total number of full sit-to-stands participants could perform were measured over a 30-second period at each visit.
Outcome measures
| Measure |
PENFS (Post-pre)
n=9 Participants
Veterans with fibromyalgia who meet study criteria and are randomized to the experimental group will receive standard therapy in addition to percutaneous electrical neural field stimulation (PENFS). This column shows the number of voxels in clusters that showed increased or decreased connectivity following treatment, \>40 voxel clusters, thresholded at p\<0.05 in AFNI.
|
Standard Therapy Control (Post-pre)
n=7 Participants
Veterans with fibromyalgia who meet study criteria and are randomized to the control group will receive standard therapy including medications and physical therapy. This column shows the number of voxels in clusters that showed increased or decreased connectivity following standard therapy, \>40 voxel clusters, thresholded at p\<0.05 in AFNI.
|
|---|---|---|
|
Change in Sit-to Stand Test From Baseline
2 weeks
|
2.7 sit-to-stands
Interval -3.9 to 9.3
|
0.3 sit-to-stands
Interval -7.8 to 8.4
|
|
Change in Sit-to Stand Test From Baseline
6 weeks
|
3.1 sit-to-stands
Interval -6.6 to 12.8
|
0.3 sit-to-stands
Interval -7.8 to 8.4
|
|
Change in Sit-to Stand Test From Baseline
12 weeks
|
1.7 sit-to-stands
Interval -7.0 to 10.4
|
1.4 sit-to-stands
Interval -6.3 to 9.1
|
Adverse Events
PENFS
Standard Therapy
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
PENFS
n=12 participants at risk
Veterans with fibromyalgia who meet study criteria and are randomized to the experimental group will receive standard therapy in addition to percutaneous electrical neural field stimulation (PENFS), which involves placement of small electrodes through a similar process to ear acupuncture to the ear. These electrodes are attached to a battery pack that is taped behind the ear and worn for 5-day intervals. The intention of this FDA-approved device is to relieve pain, though data on its effectiveness is still limited. Device placement (series of 4, weekly) will be performed by an Anesthesiology Pain Clinic provider. fMRI evaluation of neural changes, assessment of function and quality of life improvements will be performed at the beginning and end of the study.
|
Standard Therapy
n=9 participants at risk
Veterans with fibromyalgia who meet study criteria and are randomized to standard therapy will receive physical therapy, medication management through the Anesthesiology Pain Clinic, and referral to a pain psychologist. fMRI evaluation of neural changes, assessment of function and quality of life improvements will be performed at the beginning and end of the study.
Standard Therapy: Standard therapy for fibromyalgia will include physical therapy, medication management through the Anesthesiology Pain Clinic, and referral to a pain psychologist.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Skin Irritation
|
16.7%
2/12 • 2 years
|
0.00%
0/9 • 2 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place