Effects of tDCS and tUS on Pain Perception in OA of the Knee

Study Overview
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Brief Summary
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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.

Official Title
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Effects of Transcranial Direct Current Stimulation (tDCS) and Transcranial Ultrasound (TUS) on the Perception of Pain and Functional Limitations Due to Osteoarthritis of the Knee

Conditions
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Chronic Pain, Osteoarthritis

Intervention / Treatment
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* Device: active low-intensity transcranial electrical stimulation/active transcranial ultrasound
* Device: Sham low-intensity transcranial electrical stimulation/sham transcranial ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide informed consent to participate in the study. Subjects between 18-85 years old. Diagnosis of chronic osteoarthritis with pain of either knee as self-reported. Existing knee pain of at least 3 on a 0-10 VAS scale on average over the past 6 months. Pain of at least 3 on a 0-10 VAS scale on average over the week prior to the first stimulation session. 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. Having the ability to feel pain as self-reported. Exclusion Criteria: Pregnancy or trying to become pregnant in the next 6 months. History of alcohol or drug abuse within the past 6 months as self-reported Contraindications to transcranial brain stimulation or TUS, i.e. implanted brain medical devices or implanted brain metallic devices. Unstable medical conditions (e.g. uncontrolled diabetes, uncompensated cardiac issues, heart failure or chronic obstructive pulmonary disease). Epilepsy. Use of carbamazepine within the past 6 months as self-reported. Suffering from severe depression (with a score of >30 in the Beck Depression Inventory) History of unexplained fainting spells as self-reported. Head injury resulting in more than a momentary loss of consciousness History of neurosurgery as self-reported.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: tDCS and tUS
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Electrical Stim/Active Ultrasound<br>Subjects will undergo active low-intensity transcranial electrical stimulation in conjunction with active transcranial ultrasound for 20 minutes. | Device: active low-intensity transcranial electrical stimulation/active transcranial ultrasound<br>* 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.<br>|
| Sham Comparator: Sham Electrical Stim/Sham Ultrasound<br>Subjects will undergo sham (placebo) low-intensity transcranial electrical stimulation in conjunction with sham transcranial ultrasound for 20 minutes. | Device: Sham low-intensity transcranial electrical stimulation/sham transcranial ultrasound<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Baseline and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Daily Dose of Acetaminophen Equivalent | Analgesic use (average daily dose of acetaminophen equivalent) | 8 weeks | 
| 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. | Baseline and 4 weeks post-stimulation | 
| 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. | Baseline and 8 weeks | 
| 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. | Baseline and 8 weeks | 
| 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. | Baseline and 8 weeks | 
| 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. | Baseline and 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-invasive brain stimulation, transcranial direct current stimulation, transcranial ultrasound