Fibromyalgia
Conditions
Brief summary
This trial aims at understanding the mechanisms of optimized transcranial direct current stimulation (tDCS) (16 tDCS sessions combined with exercise)\] on pain control. Optimized tDCS can lead to stronger engagement of the endogenous pain regulatory system that will ultimately lead to increased pain relief in patients with fibromyalgia (FM). Therefore, the investigators designed a 2x2 factorial mechanistic trial \[tDCS (active and sham) and aerobic exercise (AE) (active and control)\] to evaluate the effects of 4 weeks of tDCS coupled with exercise on the endogenous pain regulatory system assessed by conditioned pain modulation (CPM) and central sensitization as assessed by temporal slow pain summation (TSPS), and compared to either intervention alone and to no intervention.
Detailed description
Recent evidence has suggested that FM pain can be related to deficits in pain endogenous regulatory control and that novel non-pharmacological interventions, such as tDCS can modulate this system and, consequently, reduce pain intensity. Widespread pain in FM is thought to represent enhanced pain sensitivity that is maintained by central mechanisms. This suggests changes in the descending pain control mechanisms and a possible relationship with the central sensitization phenomenon. Recent evidence has suggested that pain inhibitory pathways are affected in FM; thus, further understanding these pathways' role can significantly change how the treatment of this condition. In this study the investigators will test the effects of two interventions -tDCS and aerobic exercise - on the modulation of the endogenous inhibitory pain system in fibromyalgia.
Interventions
DEVICEActive tDCS
Active tDCS: A 1x1 Low-intensity DC Stimulator will be used to deliver direct current through rubber electrodes in saline soaked sponges. The anode will be placed over the left primary motor cortex (M1) while the cathode will be placed over the contralateral supra-orbital area. 20 minutes of tDCS will be applied.
PROCEDUREActive Exercise
Participants will walk briskly in a treadmill (as to keep at 60-70% maximum heart rate) for 30 minutes
DEVICESham tDCS
Active tDCS: A 1x1 Low-intensity DC Stimulator will be used to deliver direct current through rubber electrodes in saline soaked sponges. The anode will be placed over the left primary motor cortex (M1) while the cathode will be placed over the contralateral supra-orbital area. Only 30 seconds of current will be applied for the sham condition.
PROCEDURESham Exercise
Participants will walk in a treadmill (as to keep at 10% within their baseline heart rate) for 30 minutes.
Sponsors
Spaulding Rehabilitation Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age range 18-65 years, 2. Diagnosis of FM pain according to the ACR 2010 criteria (existing pain for more than 6 months with an average of at least 4 on a 0-10 VAS scale) without other comorbid chronic pain diagnosis, 3. Pain resistant to common analgesics and medications for chronic pain such as Tylenol, Aspirin, Ibuprofen, Soma, Parafon Forte DCS, Zanaflex, and Codeine, 4. Must have the ability to feel sensation by Von-Frey fiber on the forearm, 5. Able to provide informed consent to participate in the study.
Exclusion criteria
1. Clinically significant or unstable medical or psychiatric disorder, 2. history of substance abuse within the past 6 months as self-reported (if subject reports a history of substance abuse, we will confirm using DSM V criteria), 3. Previous significant neurological history (e.g., traumatic brain injury), resulting in neurological deficits, such as cognitive or motor deficits, as self-reported, 4. Previous neurosurgical procedure with craniotomy, 5. Severe depression (If a patient scores \>30 on the Beck Depression Inventory, one will obtain clearance. If one does not pass the medical clearance, one will not be included in the study) 6. Pregnancy (as the safety of tDCS in pregnant population (and children) has not been assessed (though risk is non-significant), the investigators will exclude pregnant women (and children). Women of child-bearing potential will be required to take a urine pregnancy test during the screening process and at every week of stimulation), 7. Current opiate use in large doses (more than 30mg of oxycodone/hydrocodone or 7.5mg of hydromorphone (Dilaudid) or equivalent), 8. Patients will be excluded when they have increased risk for exercise
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Conditioning Pain Modulation (CPM) | 6 weeks | Pain intensity was measured using the Numeric Pain Scale (NPS; 0 = no pain, 10 = worst pain). Higher scores indicate worse pain. A pain-6 temperature was first identified (temperature that elicits NPS = 6). Test stimulus: Pain-6 temperature applied for 30s; participants rated pain at 10, 20, and 30s. The test-stimulus score is the average of the three NPS ratings. Conditioned stimulus: After 5 minutes, the left hand was immersed in 10-12°C water for 30s while the same pain-6 temperature was applied again. Pain was rated the same way, and the conditioned-stimulus score is the average of the three NPS ratings. CPM calculation = (test-stimulus average) - (conditioned-stimulus average). Positive values = better endogenous pain inhibition; negative values = worse. |
| Temporal Slow Pain Summation (TSPS) | 6 weeks | Participants first determined the temperature that elicited Numeric Pain Scale (NPS) = 6 (pain-6). Using this temperature, a train of 15 heat pulses (0.4 Hz) was delivered to the right forearm with a TSA-II thermode. Pain was rated using the NPS after the 1st and 15th heat stimulus. TSPS calculation: TSPS = NPS rating after the 15th stimulus - NPS rating after the 1st stimulus. Higher TSPS values represent greater temporal pain summation (worse outcome). |
Countries
United States
Participant flow
Pre-assignment details
116 subjects were enrolled and randomized
Participants by arm
| Arm | Count |
|---|---|
| Active tDCS and Active Exercise Active tDCS for 20 min Active exercise (60-70% max HR) for 30 min
Active tDCS: Active tDCS: A 1x1 Low-intensity DC Stimulator will be used to deliver direct current through rubber electrodes in saline soaked sponges. The anode will be placed over the left primary motor cortex (M1) while the cathode will be placed over the contralateral supra-orbital area. 20 minutes of tDCS will be applied.
Active Exercise: Participants will walk briskly in a treadmill (as to keep at 60-70% maximum heart rate) for 30 minutes | 28 |
| Sham tDCS and Active Exercise Sham tDCS for 20 min Active exercise (60-70% max HR) for 30 min
Active Exercise: Participants will walk briskly in a treadmill (as to keep at 60-70% maximum heart rate) for 30 minutes
Sham tDCS: Active tDCS: A 1x1 Low-intensity DC Stimulator will be used to deliver direct current through rubber electrodes in saline soaked sponges. The anode will be placed over the left primary motor cortex (M1) while the cathode will be placed over the contralateral supra-orbital area. Only 30 seconds of current will be applied for the sham condition. | 28 |
| Active tDCS and Sham Exercise Active tDCS for 20 min Sham exercise (within 10% baseline HR) for 30 min
Active tDCS: Active tDCS: A 1x1 Low-intensity DC Stimulator will be used to deliver direct current through rubber electrodes in saline soaked sponges. The anode will be placed over the left primary motor cortex (M1) while the cathode will be placed over the contralateral supra-orbital area. 20 minutes of tDCS will be applied.
Sham Exercise: Participants will walk in a treadmill (as to keep at 10% within their baseline heart rate) for 30 minutes. | 30 |
| Sham TDCS and Sham Exercise Sham tDCS for 20 min Sham exercise (within 10% baseline HR) for 30 min
Sham tDCS: Active tDCS: A 1x1 Low-intensity DC Stimulator will be used to deliver direct current through rubber electrodes in saline soaked sponges. The anode will be placed over the left primary motor cortex (M1) while the cathode will be placed over the contralateral supra-orbital area. Only 30 seconds of current will be applied for the sham condition.
Sham Exercise: Participants will walk in a treadmill (as to keep at 10% within their baseline heart rate) for 30 minutes. | 30 |
| Total | 116 |
Baseline characteristics
| Characteristic | Active tDCS and Active Exercise | Total | Sham TDCS and Sham Exercise | Active tDCS and Sham Exercise | Sham tDCS and Active Exercise |
|---|---|---|---|---|---|
| Age, Continuous | 46.8 years STANDARD_DEVIATION 12.5 | 47.1 years STANDARD_DEVIATION 11.9 | 46.2 years STANDARD_DEVIATION 13.3 | 49.1 years STANDARD_DEVIATION 10.2 | 46.3 years STANDARD_DEVIATION 11.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants | 89 Participants | 20 Participants | 23 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 21 Participants | 6 Participants | 6 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 6 Participants | 4 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 10 Participants | 3 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 11 Participants | 3 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 5 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 20 Participants | 85 Participants | 21 Participants | 23 Participants | 21 Participants |
| Sex: Female, Male Female | 25 Participants | 103 Participants | 26 Participants | 28 Participants | 24 Participants |
| Sex: Female, Male Male | 3 Participants | 13 Participants | 4 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 28 | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 23 / 28 | 21 / 28 | 18 / 30 | 28 / 30 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 | 0 / 30 | 1 / 30 |
Outcome results
Primary
Conditioning Pain Modulation (CPM)
Pain intensity was measured using the Numeric Pain Scale (NPS; 0 = no pain, 10 = worst pain). Higher scores indicate worse pain. A pain-6 temperature was first identified (temperature that elicits NPS = 6). Test stimulus: Pain-6 temperature applied for 30s; participants rated pain at 10, 20, and 30s. The test-stimulus score is the average of the three NPS ratings. Conditioned stimulus: After 5 minutes, the left hand was immersed in 10-12°C water for 30s while the same pain-6 temperature was applied again. Pain was rated the same way, and the conditioned-stimulus score is the average of the three NPS ratings. CPM calculation = (test-stimulus average) - (conditioned-stimulus average). Positive values = better endogenous pain inhibition; negative values = worse.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active tDCS and Active Exercise | Conditioning Pain Modulation (CPM) | 0.36 Unit on a scale (NPS 0-10) |
| Sham tDCS and Active Exercise | Conditioning Pain Modulation (CPM) | 0.05 Unit on a scale (NPS 0-10) |
| Active tDCS and Sham Exercise | Conditioning Pain Modulation (CPM) | 0.21 Unit on a scale (NPS 0-10) |
| Sham TDCS and Sham Exercise | Conditioning Pain Modulation (CPM) | -0.55 Unit on a scale (NPS 0-10) |
Primary
Temporal Slow Pain Summation (TSPS)
Participants first determined the temperature that elicited Numeric Pain Scale (NPS) = 6 (pain-6). Using this temperature, a train of 15 heat pulses (0.4 Hz) was delivered to the right forearm with a TSA-II thermode. Pain was rated using the NPS after the 1st and 15th heat stimulus. TSPS calculation: TSPS = NPS rating after the 15th stimulus - NPS rating after the 1st stimulus. Higher TSPS values represent greater temporal pain summation (worse outcome).
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active tDCS and Active Exercise | Temporal Slow Pain Summation (TSPS) | -0.11 Unit on a scale (NPS 0-10) |
| Sham tDCS and Active Exercise | Temporal Slow Pain Summation (TSPS) | 0.48 Unit on a scale (NPS 0-10) |
| Active tDCS and Sham Exercise | Temporal Slow Pain Summation (TSPS) | 0.47 Unit on a scale (NPS 0-10) |
| Sham TDCS and Sham Exercise | Temporal Slow Pain Summation (TSPS) | 0.09 Unit on a scale (NPS 0-10) |