Chronic Pain, Osteoarthritis
Conditions
Keywords
transcranial direct current stimulation, transcranial ultrasound, non-invasive brain stimulation
Brief summary
The purpose of this study is to investigate the effects of transcranial direct current stimulation (tDCS) in conjunction with transcranial ultrasound (TUS) on pain perception and functional limitations in people with osteoarthritis of the knee. The investigators hypothesize that there will be a decrease in pain levels with active stimulation, when compared to sham stimulation.
Interventions
DEVICEactive low-intensity transcranial electrical stimulation/active transcranial ultrasound
Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation of up to 2mA. During active stimulation, the current will be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for the full 20 minutes.
DEVICESham low-intensity transcranial electrical stimulation/sham transcranial ultrasound
Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation, as in the active condition; however, during sham stimulation (placebo) the current will not be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound in the same par. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.
Sponsors
Highland Instruments, Inc.
Spaulding Rehabilitation Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
tDCS and tUS
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Able to provide informed consent to participate in the study. 2. Subjects between 18-85 years old. 3. Diagnosis of chronic osteoarthritis with pain of either knee as self-reported. 4. Existing knee pain of at least 3 on a 0-10 VAS scale on average over the past 6 months. 5. Pain of at least 3 on a 0-10 VAS scale on average over the week prior to the first stimulation session. 6. Pain resistant to common analgesics and medications for chronic pain used as initial pain management such as Tylenol, Aspirin, Ibuprofen, Soma, Parafon Forte DCS, Zanaflex, and Codeine. 7. Having the ability to feel pain as self-reported.
Exclusion criteria
1. Pregnancy or trying to become pregnant in the next 6 months. 2. History of alcohol or drug abuse within the past 6 months as self-reported 3. Contraindications to transcranial brain stimulation or TUS, i.e. implanted brain medical devices or implanted brain metallic devices. 4. Unstable medical conditions (e.g. uncontrolled diabetes, uncompensated cardiac issues, heart failure or chronic obstructive pulmonary disease). 5. Epilepsy. 6. Use of carbamazepine within the past 6 months as self-reported. 7. Suffering from severe depression (with a score of \>30 in the Beck Depression Inventory) 8. History of unexplained fainting spells as self-reported. 9. Head injury resulting in more than a momentary loss of consciousness 10. History of neurosurgery as self-reported.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Pain Scale as Measured by VAS | Baseline and 8 weeks | Changes in the Visual Analogue Scale (VAS) for pain were measured in order to determine whether transcranial direct current stimulation in conjunction with transcranial ultrasound is effective in reducing pain in subjects with Osteoarthritis of the Knee. The VAS scale goes from 0 up to 10, where 0 means no pain at all and 10 means the worst imaginable pain and is reported following the full course of therapy. Since we are using a difference, smaller values (negative) represent a better outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Pain Scale as Measured by VAS | Baseline and 4 weeks post-stimulation | Changes in the Visual Analogue Scale (VAS) for pain were measured in order to determine whether transcranial direct current stimulation in conjunction with transcranial ultrasound is effective in reducing pain in subjects with Osteoarthritis of the Knee. The VAS scale goes from 0 up to 10, where 0 means no pain at all and 10 means the worst imaginable pain. Since we are using a difference, smaller values (negative) represent a better outcome. |
| Percentage Change in Diffuse Noxious Inhibitory Controls (DNIC) From Baseline | Baseline and 8 weeks | This measures the endogenous pain modulatory pathway. This study will evaluate DNIC in pain patients using pressure as the test stimulus, and cold water as the conditioning stimulus. DNIC will be induced approximately 1-min later by having subjects immerse their hand into a water bath maintained at 10-12˚C for approximately 1 min. Parallel to the last 30s of DNIC conditioning (cold water immersion), the pressure test stimulus will be reapplied. DNIC response will be calculated as the difference between the average of pain ratings from the test stimulus minus the average of pain ratings during the conditioned stimulus. Larger percentage change means a better outcome. |
| Average Daily Dose of Acetaminophen Equivalent | 8 weeks | Analgesic use (average daily dose of acetaminophen equivalent) |
| Percentage Change From Baseline in the Step Test | Baseline and 8 weeks | The subject was asked to stand unsupported with their feet parallel to each other in front of a step. We assessed the number of times the participant could place their foot up onto the step and return it to the floor over a 15-sec interval. Larger percentage change means a better outcome. |
| Percentage Change in Functional Reach Test From Baseline | Baseline and 8 weeks | Subject will be instructed to stand next to, but not touch the wall, and position the arm that is closer to the wall at 90 degrees of shoulder flexion with a closed fist. Smoothness of wrist movement is assessed as the subject was asked to outstretch their arm in a maximal forward reach, while maintaining a fixed base of support. Smoothness is dimensionless and is calculated as mean speed divided by peak speed. Larger percentage change means a better outcome. |
| Percentage Change From Baseline in the Single Leg Standing Balance Test | Baseline and 8 weeks | We will record the time (seconds) for which a subject is able to stand unsupported on one foot while looking straight ahead with hands on hips. Larger percentage change means a better outcome. |
Countries
United States
Participant flow
Pre-assignment details
64 subjects were enrolled and randomized
Participants by arm
| Arm | Count |
|---|---|
| Active Electrical Stim/Active Ultrasound Subjects will undergo active low-intensity transcranial electrical stimulation in conjunction with active transcranial ultrasound for 20 minutes.
active low-intensity transcranial electrical stimulation/active transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation of up to 2mA. During active stimulation, the current will be active for the full 20 minutes.
Subjects will also undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for the full 20 minutes. | 30 |
| Sham Electrical Stim/Sham Ultrasound Subjects will undergo sham (placebo) low-intensity transcranial electrical stimulation in conjunction with sham transcranial ultrasound for 20 minutes.
Sham low-intensity transcranial electrical stimulation/sham transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation, as in the active condition; however, during sham stimulation (placebo) the current will not be active for the full 20 minutes.
Subjects will also undergo 20 minutes of transcranial ultrasound in the same par. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes. | 34 |
| Total | 64 |
Baseline characteristics
| Characteristic | Active Electrical Stim/Active Ultrasound | Sham Electrical Stim/Sham Ultrasound | Total |
|---|---|---|---|
| Age, Continuous | 61.4 years STANDARD_DEVIATION 8.4 | 61.8 years STANDARD_DEVIATION 8.7 | 61.6 years STANDARD_DEVIATION 8.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 26 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 6 Participants | 10 Participants |
| Region of Enrollment United States | 30 Participants | 34 Participants | 64 Participants |
| Sex: Female, Male Female | 16 Participants | 18 Participants | 34 Participants |
| Sex: Female, Male Male | 14 Participants | 16 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 34 |
| other Total, other adverse events | 23 / 30 | 29 / 34 |
| serious Total, serious adverse events | 0 / 30 | 0 / 34 |
Outcome results
Primary
Changes in Pain Scale as Measured by VAS
Changes in the Visual Analogue Scale (VAS) for pain were measured in order to determine whether transcranial direct current stimulation in conjunction with transcranial ultrasound is effective in reducing pain in subjects with Osteoarthritis of the Knee. The VAS scale goes from 0 up to 10, where 0 means no pain at all and 10 means the worst imaginable pain and is reported following the full course of therapy. Since we are using a difference, smaller values (negative) represent a better outcome
Time frame: Baseline and 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Electrical Stim/Active Ultrasound | Changes in Pain Scale as Measured by VAS | -2.21 units on a scale | Standard Error 0.2 |
| Sham Electrical Stim/Sham Ultrasound | Changes in Pain Scale as Measured by VAS | -1.6 units on a scale | Standard Error 0.1 |
Secondary
Average Daily Dose of Acetaminophen Equivalent
Analgesic use (average daily dose of acetaminophen equivalent)
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Electrical Stim/Active Ultrasound | Average Daily Dose of Acetaminophen Equivalent | 390.7 Acetaminophen equivalent in mg | Standard Error 47.1 |
| Sham Electrical Stim/Sham Ultrasound | Average Daily Dose of Acetaminophen Equivalent | 1116.4 Acetaminophen equivalent in mg | Standard Error 98.6 |
Secondary
Changes in Pain Scale as Measured by VAS
Changes in the Visual Analogue Scale (VAS) for pain were measured in order to determine whether transcranial direct current stimulation in conjunction with transcranial ultrasound is effective in reducing pain in subjects with Osteoarthritis of the Knee. The VAS scale goes from 0 up to 10, where 0 means no pain at all and 10 means the worst imaginable pain. Since we are using a difference, smaller values (negative) represent a better outcome.
Time frame: Baseline and 4 weeks post-stimulation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Electrical Stim/Active Ultrasound | Changes in Pain Scale as Measured by VAS | -2.91 units on a scale | Standard Error 0.38 |
| Sham Electrical Stim/Sham Ultrasound | Changes in Pain Scale as Measured by VAS | -1.28 units on a scale | Standard Error 0.3 |
Secondary
Percentage Change From Baseline in the Single Leg Standing Balance Test
We will record the time (seconds) for which a subject is able to stand unsupported on one foot while looking straight ahead with hands on hips. Larger percentage change means a better outcome.
Time frame: Baseline and 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Electrical Stim/Active Ultrasound | Percentage Change From Baseline in the Single Leg Standing Balance Test | 17.5 Percentage change from baseline | Standard Error 4.5 |
| Sham Electrical Stim/Sham Ultrasound | Percentage Change From Baseline in the Single Leg Standing Balance Test | 3.0 Percentage change from baseline | Standard Error 3.1 |
Secondary
Percentage Change From Baseline in the Step Test
The subject was asked to stand unsupported with their feet parallel to each other in front of a step. We assessed the number of times the participant could place their foot up onto the step and return it to the floor over a 15-sec interval. Larger percentage change means a better outcome.
Time frame: Baseline and 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Electrical Stim/Active Ultrasound | Percentage Change From Baseline in the Step Test | 27.0 Percentage change from baseline | Standard Error 2 |
| Sham Electrical Stim/Sham Ultrasound | Percentage Change From Baseline in the Step Test | 18.7 Percentage change from baseline | Standard Error 1.8 |
Secondary
Percentage Change in Diffuse Noxious Inhibitory Controls (DNIC) From Baseline
This measures the endogenous pain modulatory pathway. This study will evaluate DNIC in pain patients using pressure as the test stimulus, and cold water as the conditioning stimulus. DNIC will be induced approximately 1-min later by having subjects immerse their hand into a water bath maintained at 10-12˚C for approximately 1 min. Parallel to the last 30s of DNIC conditioning (cold water immersion), the pressure test stimulus will be reapplied. DNIC response will be calculated as the difference between the average of pain ratings from the test stimulus minus the average of pain ratings during the conditioned stimulus. Larger percentage change means a better outcome.
Time frame: Baseline and 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Electrical Stim/Active Ultrasound | Percentage Change in Diffuse Noxious Inhibitory Controls (DNIC) From Baseline | 12 Percentage change from baseline | Standard Error 2.9 |
| Sham Electrical Stim/Sham Ultrasound | Percentage Change in Diffuse Noxious Inhibitory Controls (DNIC) From Baseline | 4.0 Percentage change from baseline | Standard Error 1.8 |
Secondary
Percentage Change in Functional Reach Test From Baseline
Subject will be instructed to stand next to, but not touch the wall, and position the arm that is closer to the wall at 90 degrees of shoulder flexion with a closed fist. Smoothness of wrist movement is assessed as the subject was asked to outstretch their arm in a maximal forward reach, while maintaining a fixed base of support. Smoothness is dimensionless and is calculated as mean speed divided by peak speed. Larger percentage change means a better outcome.
Time frame: Baseline and 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Electrical Stim/Active Ultrasound | Percentage Change in Functional Reach Test From Baseline | 12.4 Percentage change from baseline | Standard Error 2.8 |
| Sham Electrical Stim/Sham Ultrasound | Percentage Change in Functional Reach Test From Baseline | 3.3 Percentage change from baseline | Standard Error 2.3 |