title: Safety and tolerability of transcranial direct current stimulation to stroke patients - A phase I current escalation study.
abstract: A prior meta-analysis revealed that higher doses of transcranial direct current stimulation (tDCS) have a better post-stroke upper-extremity motor recovery. While this finding suggests that currents greater than the typically used 2 mA may be more efficacious, the safety and tolerability of higher currents have not been assessed in stroke patients. We aim to assess the safety and tolerability of single session of up to 4 mA in stroke patients.
  
  
  
  We adapted a traditional 3 + 3 study design with a current escalation schedule of 1»2»2.5»3»3.5»4 mA for this tDCS safety study. We administered one 30-min session of bihemispheric montage tDCS and simultaneous customary occupational therapy to patients with first-ever ischemic stroke. We assessed safety with pre-defined stopping rules and investigated tolerability through a questionnaire. Additionally, we monitored body resistance and skin temperature in real-time at the electrode contact site.
  
  
  
  Eighteen patients completed the study. The current was escalated to 4 mA without meeting the pre-defined stopping rules or causing any major safety concern. 50% of patients experienced transient skin redness without injury. No rise in temperature (range 26°C-35 °C) was noted and skin barrier function remained intact (i.e. body resistance >1 kΩ).
  
  
  
  Our phase I safety study supports that single session of bihemispheric tDCS with current up to 4 mA is safe and tolerable in stroke patients. A phase II study to further test the safety and preliminary efficacy with multi-session tDCS at 4 mA (as compared with lower current and sham stimulation) is a logical next step. ClinicalTrials.gov Identifier: NCT02763826.
authors.affiliation: Department of Neurology, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Pratik Y
authors.initials: PY
authors.lastname: Chhatbar
authors.affiliation: Department of Neurology, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Rachael
authors.initials: R
authors.lastname: Deardorff
authors.affiliation: Department of Health Science & Research, College of Health Professions, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Blair
authors.initials: B
authors.lastname: Dellenbach
authors.affiliation: Department of Health Science & Research, College of Health Professions, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Kautz
authors.affiliation: Ralph H. Johnson VA Medical Center, Charleston, SC, USA; Department of Psychiatry and Behavioral Science, Brain Stimulation Laboratory, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: George
authors.affiliation: Department of Neurology, College of Medicine, Medical University of South Carolina, Charleston, SC, USA; Department of Health Science & Research, College of Health Professions, Medical University of South Carolina, Charleston, SC, USA. Electronic address: feng@musc.edu.
authors.forename: Wuwei
authors.initials: W
authors.lastname: Feng
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000628:therapy*; D000071939:Stroke Rehabilitation / Q000009:adverse effects / Q000379:methods; D065908:Transcranial Direct Current Stimulation / Q000009:adverse effects* / Q000379:methods; D034941:Upper Extremity / Q000503:physiopathology
keywords: 3+3 design; Dose escalation; High-dose; Non-invasive brain stimulation; Stroke recovery; Transcranial direct current stimulation