Remotely-supervised transcranial direct current stimulation (tDCS) for clinical trials: guidelines for technology and protocols

Leigh E Charvet, Margaret Kasschau, Abhishek Datta, Helena Knotkova, Michael C Stevens, Angelo Alonzo, Colleen Loo, Kevin R Krull, Marom Bikson, Leigh E Charvet, Margaret Kasschau, Abhishek Datta, Helena Knotkova, Michael C Stevens, Angelo Alonzo, Colleen Loo, Kevin R Krull, Marom Bikson

Abstract

The effect of transcranial direct current stimulation (tDCS) is cumulative. Treatment protocols typically require multiple consecutive sessions spanning weeks or months. However, traveling to clinic for a tDCS session can present an obstacle to subjects and their caregivers. With modified devices and headgear, tDCS treatment can be administered remotely under clinical supervision, potentially enhancing recruitment, throughput, and convenience. Here we propose standards and protocols for clinical trials utilizing remotely-supervised tDCS with the goal of providing safe, reproducible and well-tolerated stimulation therapy outside of the clinic. The recommendations include: (1) training of staff in tDCS treatment and supervision; (2) assessment of the user's capability to participate in tDCS remotely; (3) ongoing training procedures and materials including assessments of the user and/or caregiver; (4) simple and fail-safe electrode preparation techniques and tDCS headgear; (5) strict dose control for each session; (6) ongoing monitoring to quantify compliance (device preparation, electrode saturation/placement, stimulation protocol), with corresponding corrective steps as required; (7) monitoring for treatment-emergent adverse effects; (8) guidelines for discontinuation of a session and/or study participation including emergency failsafe procedures tailored to the treatment population's level of need. These guidelines are intended to provide a minimal level of methodological rigor for clinical trials seeking to apply tDCS outside a specialized treatment center. We outline indication-specific applications (Attention Deficit Hyperactivity Disorder, Depression, Multiple Sclerosis, Palliative Care) following these recommendations that support a standardized framework for evaluating the tolerability and reproducibility of remote-supervised tDCS that, once established, will allow for translation of tDCS clinical trials to a greater size and range of patient populations.

Keywords: attention deficit hyperactivity disorder; clinical trials; depression; multiple sclerosis; palliative care; tDCS.

Figures

Figure 1
Figure 1
Example of subject checklist.
Figure 2
Figure 2
Guidelines for training.
Figure 3
Figure 3
Example of study flowchart with stop criteria.
Figure 4
Figure 4
Example of hardware-based waveform control. Users are provided with an individual device and accessories such as the 5x-Session Home Kit (A)The subject checks in with the supervisor before and after each session (B). The supervisor unlocks operation before each session by providing a code (B). The subject enters only the code provided with no access to device programming or stimulation settings. The subject uses custom fit headgear to position electrodes (C,D). The device automatically collects compliance data and may also prompt the user for information (E). Details of implementation will be customized to each clinical trial while maintaining the principles of supervised neuromodulation (F, G). (Image courtesy of Soterix Medical Inc.)
Figure 5
Figure 5
Example of software-based waveform control. Users are provided with an individual stimulator, a discharge key, and accessories such as the 5x-Session Home Kit. The supervisor limits stimulation by programming the discharge key. The subject plugs the discharge key into the device and presses a single button to activate stimulation. The subject uses custom fit headgear to position electrodes. The device automatically collects compliance data which is stored in the discharge key. Details of device implementation will be customized to each clinical trial while maintaining the principles of supervised neuromodulation. (Image courtesy of Soterix Medical Inc.)
Figure 6
Figure 6
Guidelines for study equipment.
Figure 7
Figure 7
Guidelines for ongoing assessment.

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