The goal of this pilot study is to describe a protocol for the remotely-supervised delivery of transcranial direct current stimulation (tDCS) so that the procedure maintains standards of in-clinic practice, including safety, reproducibility, and tolerability. The feasibility of this protocol was tested in participants with multiple sclerosis (MS).
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low amplitude direct currents to alter cortical excitability. With well-established safety and tolerability, tDCS has been found to have the potential to ameliorate symptoms such as depression and pain in a range of conditions as well as to enhance outcomes of cognitive and physical training. However, effects are cumulative, requiring treatments that can span weeks or months and frequent, repeated visits to the clinic. The cost in terms of time and travel is often prohibitive for many participants, and ultimately limits real-world access.
Following guidelines for remote tDCS application, we propose a protocol that would allow remote (in-home) participation that uses specially-designed devices for supervised use with materials modified for patient use, and real-time monitoring through a telemedicine video conferencing platform. We have developed structured training procedures and clear, detailed instructional materials to allow for self- or proxy-administration while supervised remotely in real-time. The protocol is designed to have a series of checkpoints, addressing attendance and tolerability of the session, to be met in order to continue to the next step. The feasibility of this protocol was then piloted for clinical use in an open label study of remotely-supervised tDCS in multiple sclerosis (MS). This protocol can be widely used for clinical study of tDCS.
tDCS is a relatively recent therapy that operates through the use of low amplitude (2.0 mA or less) direct current to modulate cortical excitability 1. Hundreds of clinical trials have demonstrated tDCS to be safe and well-tolerated2-4. tDCS is easier to use, lower in cost, and better tolerated when compared to other methods such as transcranial magnetic stimulation (e.g., tDCS has not been associated with the development of seizures 5,6). Multiple tDCS sessions are required for benefit, especially when administered with the goal of enhancing rehabilitation outcomes.7-10
It is not yet known how many tDCS sessions are necessary or optimal, but the effects are cumulative with little evidence that tDCS over a single session produces behaviorally meaningful changes.2,11 For example, studies of depression have found 30 or more sessions needed for full benefit in some participants. 12,13 Multiple sessions are especially important when pairing tDCS with a behavioral therapy, which only occurs with rigorous repetition across many sessions. 14
For many patients and caregivers, traveling to the outpatient facility to receive repeated tDCS treatment sessions is a major obstacle in terms of time, cost and travel arrangements. This real-world limitation has resulted in studies with small sample sizes and without adequate power or design to draw conclusions that can lead to clinical use.15 Remote tDCS delivery would allow for participation in study protocols from home or other locations, and reach those patients who otherwise would not have access to these trials. Further, it allows the possibility for testing “on-demand” application for indications such as epilepsy and migraines.
We have worked with a diverse group of clinical investigators interested in remotely-supervised tDCS to develop guidelines and standards for remotely-supervised tDCS delivery including specialized equipment and specific training requirements both for staff and study participants16. Here, we developed a protocol to follow these guidelines and test for feasibility in patients with multiple sclerosis (MS), a disorder where tDCS may be a useful tool for the management of its symptoms. 11,17-23
Critical steps within the protocol
As remotely-supervised tDCS is administered away from the direct supervision of a clinician, inclusion and exclusion criteria are designed to ensure that the participant has no contraindicated health conditions or environmental distractions, and are fully capable to use a laptop computer (including those with adaptive technology) for communication with the research team. In addition, participants must be able to tolerate a tDCS session and commit to the scheduled session time for the duration of the study.
While remote tDCS offers a convenience to the study and administration of the therapy, self-directed participant use is not advisable due to both safety concerns and the inability to monitor and standardize the stimulation that is delivered. Instead, our protocol follows the standards and guidelines for remotely-supervised tDCS16 to extend clinic standards through delivery in a remote location. The guidelines ensure that research staff are properly trained for participant interactions, that users have proper ability to participate in remote tDCS, and that there are ongoing training materials as well as assessments made of the participant at each step of the study. The stimulation was uniform and reproducible with exactly 20 min of 1.5 mA delivered at every session without any interruption or variation across sessions or individuals.
Modifications to the protocol and troubleshooting tips
The protocol includes several small modifications. Firstly, we expanded the use of this protocol to MS participants that have an EDSS score above 6.5 in the instance where there is a proxy accessible to administer each dose. In addition, we have implemented a procedure whereby we remotely access the participant's study provided laptop to initiate the web conference for those who need extra support and review measures of tolerability and study experiences through a shared document. A future modification to the current protocol includes allowing various degrees of remote supervision so that participants who prove most competent with the technique would only require early supervision to confirm device set up and to receive the unlock code.
Limitations of the technique
While our preliminary results support the feasibility of this protocol, the sample size is limited. As enrollment expands, analyses will be made for gaps in training, ways to streamline sessions, enhance the instructional video, and make the technique more accessible to those with motor impairment (i.e., adaptive mice for computer usage, sponge pocket/headset modification to further ease application). Some participants in the EDSS range below 6.5 (not requiring proxy), may still experience some difficulty in headset preparation and troubleshooting computer related issues. Furthermore, while this study recommends full remote monitoring of participants throughout all sessions, future studies may deem some participants sufficiently trained to operate the device without supervision for the entirety of a session.
Significance of the method with respect to existing methods
These initial results demonstrate the feasibility of our protocol for remotely-supervised tDCS delivery for clinical trials, following a set of guidelines and standards that must be employed to safely, and effectively administer tDCS under remote supervision. The protocol was designed to have a decision-tree series of checkpoints with "stop" criteria (section 2.5.1 above) that must be cleared in order to proceed at each step (see Figure 1). These checkpoints addressed tolerability (experiences of pain or adverse effects to the treatment) and compliance (timely session attendance and proper technique). For each session 1 through 10, participants completed brief adverse event reports before and after their sessions (with items derived from a list of the most common tDCS side-effects in previous trials). In addition, participants completed the self-report measures to address tolerability (before and after the session) and can complete symptom inventories as well. This study is significant in that it establishes a technique to examine a therapy in MS with adequate power while also providing broader access to tDCS treatment.
Future applications of the technique
Once the method for remotely-supervised tDCS has been fully piloted in the MS population, a larger, randomized controlled trial can be initiated to target symptom management. Through the use of the instructional training materials and structure around daily participant interactions, remotely-supervised tDCS can be accessed by a wider range of patient populations and expand clinical study of the technique.
The authors have nothing to disclose.
Supported by The Lourie Foundation, Inc.
Mini-CT transcranial direct current stimulation device | Soterix | Device to deliver direct current stimultion in a remote manner | |
Study Kit | NA | Provided to participant with all required setup items – device, headset, sponge pockets, pre-filled syringes, Kleenex, handheld mirro, spare batteries | |
Laptop | NA | Provided to allow secure video conferecing during device setup and headset placement | |
Instruction Manual | NA | Transcription of instructional video and detailed instructions for protocol |