Safety and Efficacy of tDCS in Pediatric DoC

NCT05929274 | Withdrawn

• 1 other identifier: tDCS-DoC-Ped
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: Despite established evidence supporting the use of tDCS in the adult patient with disorders of consciousness, its use in paediatric patients with brain injury is still limited. Regarding the use of tDCS in paediatric patients with DoC, the scientific evidence still appears to be preliminary about the safety profile and requires further data before investigating efficacy on a broad scale. In fact, although the method has been shown to be safe in other clinical conditions, efficacy and tolerability in children with DoC may vary significantly depending on differences in activation threshold and the presence of underlying pathological electrical activity The implementation of clinical trials investigating the safety and tolerability of tDCS in paediatric patients with DoC now represents an essential first step for a future determination of the efficacy of this method in a population for which therapeutic options are currently extremely limited Objective: The study aim to verify the safety of tDCS treatment and to evaluate the effectiveness of stimulation of the left dorsolateral prefrontal cortex by tDCS in promoting improvement in the level of consciousness in paediatric patients with Disorders of Consciousness. Method: in this mono-center, randomised, double blind cross-over controlled pilot study, real or sham tDCS were applied to the left dorsolateral prefrontal (DLPF) cortex of paediatric patients with disorders of consciousness for two weeks, followed by two weeks of washout, then real or sham tDCS were applied to the left dorsolateral prefrontal (DLPF) cortex for other two weeks, followed by another two weeks of washout.

Conditions

Disorder of Consciousness

Keywords

Pediatric population; tDCS; disorder of consciousness

Outcome Measures

Primary Outcomes (3)

• Evaluating the safety of tDCS treatment assessing the change over time

  the ratio of reported adverse events between the two treatment groups and the proportion of treatments discontinued for adverse events will be assessed, using an "Adverse Event Collection Form" completed by a practitioner other than the parents will be used

  baseline (1-7 days), post-stimulation (within 30-minutes), follow-up (24 hours, 48 hours, 5 days)

• Assessing the change of tolerability of treatment with tDCS

  Face, Legs, Activity, Cry and Consolability Scale (FLACC 0-10 worst value) scale will be used to assess tolerability of treatment

  Baseline (1-7 days), pre-during-post stimulation (pre-stimulation: within 30 minutes, during: within 20 minutes, post-stimulation: within 30-minutes)

• Assessing the change in the state of consciousness by using tDCS

  Coma Recovery Scale - Revised (CRS-R 0-23 best value) will be used to evaluate the effectiveness of tDCS

  days 1, 8, 12, 19, 35, 40, 47, 62, 92

Secondary Outcomes (4)

• To evaluate the effect of tDCS stimulation on brain electrical activity

  days 1, 8, 35, 47, 62, 92

• To evaluate the effect of tDCS stimulation on cortical electrical activity

  days 1, 8, 35, 47, 62, 92

• To evaluate the effect of tDCS stimulation in determining haemodynamic response (HDR) changes quantifiable

  days 8, 35, 47, 62, 92

• Assess caregiver satisfaction with the treatment

  days 19 and 47

Study Arms (2)

Active Comparator - real tDCS

EXPERIMENTAL

real tDCS: anodal transcranial direct current stimulation were delivered over the left DLPF cortex in patients

Device: tDCS

Sham Comparator - sham tDCS

SHAM COMPARATOR

sham transcranial direct current stimulation were delivered over the left DLPF cortex in patients.

Device: sham tDCS

Interventions

tDCS DEVICE

Direct current was applied by a battery-driven constant current stimulator using saline-soaked surface sponge electrodes (7 3 5 cm) with the anode positioned over the left dorsolateral prefrontal cortex (F3 according to the 10-20 international system for EEG placement) and the cathode placed over the right supraorbital region. During real tDCS, the current was increased to 2 milliampere (mA) from the onset of stimulation and applied for 20 minutes.

Active Comparator - real tDCS

sham tDCS DEVICE

For the sham condition (sham tDCS), the same electrode placement was used as in the stimulation condition, but the current was applied for only 5 seconds, and was then ramped down.

Sham Comparator - sham tDCS

Eligibility Criteria

• Age: 4 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Ages between 4 and 17;
• prolonged condition (\>3 and \<12 months) of MCS and VS by severe brain injury;
• admission to the paediatric rehabilitation department of the Don Carlo Gnocchi Foundation in Florence;
• central nervous system drug therapy stable for at least one week;
• stable DoC (i.e. no change in DoC diagnosis detected by 2 consecutive CRS-Rs performed one week apart);
• Signature of informed consent by the legal representative.

You may not qualify if:

• Presence of extensive focal lesions in the left dorsolateral prefrontal cortex (DLPFC);
• radiological evidence of blood collection/liquid collection/other between the DLPFC and the anode placement site;
• seizures in the previous month;
• seizures and/or intermittent epileptiform discharges observed at the extended EEG during the screening phase or at any of the EEG recordings during participation in the study;
• Presence of established pregnancy;
• History of cranial surgery, presence of metallic, cochlear or electronic brain implant in the head or neck area, or ventricular shunt to pacemaker;
• Need for mechanical daytime ventilation;
• Head circumference less than 43 cm;
• bilateral severe or profound hypoacusia;
• Presence of skin lesions in the area to be stimulated;
• Taking sedative drugs and/or Na or Ca channel blockers or NMDA receptor antagonists presence of peritoneal ventricle shunt in the stimulated area (prefrontal cortex);
• serious clinical conditions that may influence the clinical diagnosis (e.g. severe liver failure or kidney).

Sponsors & Collaborators

• Giovanna Cristella: lead

Related Publications (7)

• Chung MG, Lo WD. Noninvasive brain stimulation: the potential for use in the rehabilitation of pediatric acquired brain injury. Arch Phys Med Rehabil. 2015 Apr;96(4 Suppl):S129-37. doi: 10.1016/j.apmr.2014.10.013. Epub 2014 Nov 6.

  PMID: 25448248 BACKGROUND

• Elbanna ST, Elshennawy S, Ayad MN. Noninvasive Brain Stimulation for Rehabilitation of Pediatric Motor Disorders Following Brain Injury: Systematic Review of Randomized Controlled Trials. Arch Phys Med Rehabil. 2019 Oct;100(10):1945-1963. doi: 10.1016/j.apmr.2019.04.009. Epub 2019 May 10.

  PMID: 31078616 BACKGROUND

• Estraneo A, Pascarella A, Moretta P, Masotta O, Fiorenza S, Chirico G, Crispino E, Loreto V, Trojano L. Repeated transcranial direct current stimulation in prolonged disorders of consciousness: A double-blind cross-over study. J Neurol Sci. 2017 Apr 15;375:464-470. doi: 10.1016/j.jns.2017.02.036. Epub 2017 Feb 17.

  PMID: 28320187 BACKGROUND

• Giacino JT, Whyte J, Bagiella E, Kalmar K, Childs N, Khademi A, Eifert B, Long D, Katz DI, Cho S, Yablon SA, Luther M, Hammond FM, Nordenbo A, Novak P, Mercer W, Maurer-Karattup P, Sherer M. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med. 2012 Mar 1;366(9):819-26. doi: 10.1056/NEJMoa1102609.

  PMID: 22375973 BACKGROUND

• Hameed MQ, Dhamne SC, Gersner R, Kaye HL, Oberman LM, Pascual-Leone A, Rotenberg A. Transcranial Magnetic and Direct Current Stimulation in Children. Curr Neurol Neurosci Rep. 2017 Feb;17(2):11. doi: 10.1007/s11910-017-0719-0.

  PMID: 28229395 BACKGROUND

• Palm U, Segmiller FM, Epple AN, Freisleder FJ, Koutsouleris N, Schulte-Korne G, Padberg F. Transcranial direct current stimulation in children and adolescents: a comprehensive review. J Neural Transm (Vienna). 2016 Oct;123(10):1219-34. doi: 10.1007/s00702-016-1572-z. Epub 2016 May 12.

  PMID: 27173384 BACKGROUND

• Saleem GT, Ewen JB, Crasta JE, Slomine BS, Cantarero GL, Suskauer SJ. Single-arm, open-label, dose escalation phase I study to evaluate the safety and feasibility of transcranial direct current stimulation with electroencephalography biomarkers in paediatric disorders of consciousness: a study protocol. BMJ Open. 2019 Aug 10;9(8):e029967. doi: 10.1136/bmjopen-2019-029967.

  PMID: 31401607 BACKGROUND

MeSH Terms

Conditions

Consciousness Disorders

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Giovanna Cristella, MD

  IRCCS Fondazione Don Carlo Gnocchi ONLUS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Using a sham-controlled randomized double-blind design, 10 patients were randomly assigned to group A or B.

Study Record Dates

• First Submitted: May 9, 2023
• First Posted: July 3, 2023
• Study Start: January 1, 2024
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share