Transcranial Direct Current Stimulation and Chronic Pain

Study Overview
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Brief Summary
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This clinical trial uses transcranial direct current stimulation (tDCS) using the patented tKIWI system to safely reduce self-reported chronic pain with little to no side effects to improve our understanding and ability to accurately diagnose pain disorders which would facilitate the development of pharmacologic and non-pharmacologic treatment modalities using deep learning architecture built into the tKIWI.

Detailed Description
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Pain is a severe and growing problem in the United States with more than 116 million Americans suffering from chronic pain and more than $635 billion is spent annually on pain and its related healthcare costs. Additionally, opioid addiction has become a national crisis with nearly 50,000 deaths every year as a result of opioid-involved overdoses and nearly $78.5 billion spent annually on opioid misuse and addiction. Currently available treatments for pain, namely opioid analgesics, have limited effectiveness and can lead to a significant number of side effects and complications including dependence, pharmacodynamic tolerance, sedation, gastrointestinal issues, respiratory depression, immunosuppression, and hormonal changes. Effectively treating pain requires an accurate assessment of pain, however current methods of diagnosing and evaluating pain depend on subjective self-reporting including the use of visual and numerical pain scales. The subjective nature of describing pain makes it virtually impossible to quantify and therefore difficult to treat and monitor. To overcome this subjectivity, through a non-invasive neuromodulation technique called transcranial direct current stimulation (tDCS) and deep learning, pain can be measured objectively using electroencephalograph (EEG) to assess and personalize treatment. The overarching goal of this project is to apply transcranial direct current stimulation (tDCS) as an alternative to opioids for the reduction in chronic pain. The investigator's long-term goal is to use these data to analyze EEG signals and generate personalized tDCS treatment in real time.

Official Title
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Toward Personalized Treatment of Chronic Pain Using Transcranial Direct Current Stimulation Paired With Deep Learning

Conditions
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Chronic Pain

Intervention / Treatment
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* Device: Transcranial Direct Current Stimulation (tDCS)
* Device: Transcranial Direct Current Stimulation (tDCS) sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-79 years old Gender: Any Ethnicity: Any Chronic pain (> 3-months); No current use of nonprescription opioids (< 1 month); Able and willing to comply with scheduled visits and other study-related procedures to complete the study; Willing and able to give informed consent. Exclusion Criteria: Diagnosis (as defined by DSM-IV) of: any psychotic disorder (lifetime); eating disorder (current or within the past year); obsessive compulsive disorder (lifetime)); mental retardation. History of drug or alcohol abuse or dependence (as per DSM-IV criteria) within the last 3 months (except nicotine and caffeine). Subject is on regular benzodiazepine medication which it is not clinically appropriate to discontinue. Subject requires a rapid clinical response due to inanition, psychosis or high suicide risk. Neurological disorder or insult, e.g., recent stroke (CVA), which places subject at risk of seizure or neuronal damage with tDCS. Subject has metal in the cranium, skull defects, or skin lesions on scalp (cuts, abrasions, rash) at proposed electrode sites. Female subject who is pregnant. Participants who are not fluent in English will not be included in the trial for safety reasons: a) It is usually not possible to have an interpreter reliably available every weekday for up to 4 weeks and it is not safe to give tDCS to a subject who cannot tell us immediately of any side effects; Note that translation of the proposed ACT activity into English has not been validated and that we cannot be confident that they would be accurately translated and validated. Minors Older than 79 years old last use >24 months history of EEG or any electrical implant (i.e. pacemaker) history of Parkinson's, diagnosis of bipolar, schizophrenia/schizo-affective d/o, OCD, epilepsy, alzheimers taking antipsychotic drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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: The proposed study employs a randomized, double-blind, sham-controlled design to evaluate the effects of the tDCS using the tKIWI device on chronic pain. The participant will be randomly assigned to the treatment (tx) or sham/placebo group. Up to 40 participants will be recruited and randomly placed in either the treatment or the sham group. The randomization ratio is 1:1. Each participant has an equal chance of being assigned to each condition and each participant will be assigned to a condition independently of the other participants. The sample is small (20 each group), so in order to ensure random assignment, we will assign a unique number to every participant of the study's sample. Then, we will use a lottery method to randomly assign each number to the control or experimental group.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>For visits 1-5 (tDCS treatment visits), the investigators will start with 0.5mA ramping up to 0.75mA for 5 minutes. Followed by a brief (8 sec) EEG recording. Then, the investigators will apply .75mA to 1mA for 5 minutes. This will also be followed by 8 second EEG recording. The final application of current will be 1mA to 1.75mA for 10 minutes followed again by 8 second EEG recording. | Device: Transcranial Direct Current Stimulation (tDCS)<br>* TDCS is a non-invasive brain stimulation that uses electrical currents to stimulate specific areas of the brain. A constant, low-intensity current passes through two to four electrodes, which can be placed on various locations on the head, to modulate neuronal activity. tDCS can administer anodal and cathodal stimulation to excite (depolarization) or inhibit (hyperpolarization) neuronal activity, respectively. Using low-amplitude direct currents applied via scalp electrodes to alter cortical excitability is not a novel concept. This non-pharmacological approach has held promise for decades as a way to treat a plethora of neurological and psychiatric disorders. Although tDCS is not currently FDA-approved it is considered a non-significant-risk therapy with no record of serious adverse effects.<br>* Other names: ni2o;|
| Sham Comparator: Sham<br>For visits 1-5 (tDCS treatment visits),The sham group will receive 1 minute from 0.0mA to no more than 0.5mA at the initiation of the treatment after which the current will be turned off. They will still proceed with the full 20 minutes as does the treatment group but no current will be further applied as indicated in the treatment group. They will still receive EEG readings at the indicated 8 seconds after current is applied but will not receive the current. This is to maintain a blind trial. 0.5mA is negligible current but mimics treatment with an initial small tingle. | Device: Transcranial Direct Current Stimulation (tDCS) sham<br>* TDCS is a non-invasive brain stimulation that uses electrical currents to stimulate specific areas of the brain. A constant, low-intensity current passes through two to four electrodes, which can be placed on various locations on the head, to modulate neuronal activity. tDCS can administer anodal and cathodal stimulation to excite (depolarization) or inhibit (hyperpolarization) neuronal activity, respectively. Using low-amplitude direct currents applied via scalp electrodes to alter cortical excitability is not a novel concept. This non-pharmacological approach has held promise for decades as a way to treat a plethora of neurological and psychiatric disorders. The sham group will receive 1 minute from 0.0mA to no more than 0.5mA at the initiation of the treatment after which the current will be turned off. This is to maintain a blind trial. 0.5mA is negligible current, but mimics treatment with an initial small tingle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the impact of tDCS on pain in chronic pain participants using pain perception scale | The investigators will compare the baseline pain perception scale results of subjects in treatment and placebo arms to pain perception scales results on the final day of the treatment and again one week later, enabling investigators to determine any short-term change or durable change to pain. The scale is the Wong-Baker FACES® Pain Rating Scale Based on the visual representations and descriptions below, please rate your chronic pain on a scale from 1 (no pain) to 10 (worst possible pain). The measurement is done using the ranking of 1 to 10 in pain, adding up to the total of the response and the larger numbers indicate higher pain levels with no units. | 14 months | 
| Determine the impact of tDCS on the self-reported reduction in opioid use, or the desire for opioid use. | The investigators will compare baseline opioid use and desire to use opioids to final visit in both treatment and sham arms. The measurement will be a comparison in the self-reported survey Medication for Pain Management Survey. This survey has questions such as, My need for using opioid pain medication is less than before I participated in this study, and My desire to use opioid pain medication is less than before I participated in this study. These are answered using yes, no, or unknown. | 14 months | 
| Compare the safety of the tDCS system (tKIWI) versus placebo (sham) utilizing blood pressure | The investigators will achieve this aim by monitoring subjects' vitals during the entire session of each visit. The measurement is blood pressure (mmHg). | 14 months | 
| Compare the safety of the tDCS system (tKIWI) versus placebo (sham) utilizing heart rate | The investigators will achieve this aim by monitoring subjects' vitals during the entire session of each visit. The measurement is heart rate (bpm). | 14 months | 
| Compare the safety of the tDCS system (tKIWI) versus placebo (sham) utilizing heart rate | The investigators will achieve this aim by monitoring subjects' vitals during the entire session of each visit. The measurement is temperature (degrees C). | 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare changes in brain waves during tDCS treatment sessions in the treatment (tDCS) and placebo (sham) arms. | This aim will be achieved by capturing EEG readings of the entire brain for subjects in each treatment arm at baseline, during the treatment phase, and at final study visit 1 week post treatment. The EEG showcases brain wave activity in microvolts (mV). | 14 months | 
| Compare the tolerability of the tDCS system (tKIWI) versus placebo (sham) | We will achieve this aim by evaluating the results of a questionnaire after each treatment session and after the final study visit, enabling us to capture reported discomfort. The questions state Please report any side-effects as well as the intensity and persistence of reported side-effects you may have experienced during the application of transcranial direct current stimulation (tDCS)., and evaluate if there is itching, tingling, burning, redness, and headaches. If there is a symptom then the participant will note the intensity as very, a little, or barely | 14 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic pain, transcranial direct current stimulation