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Neural, Behavioural, and Clinical Effects of tDCS in PDOC; Feasibility Study

Not Applicable
Conditions
Vegetative State
Brain Injuries
Consciousness Disorder
Minimally Conscious State
Interventions
Other: Transcranial direct current stimulation
Registration Number
NCT04248946
Lead Sponsor
University of Birmingham
Brief Summary

This study evaluates the feasibility of an experimental protocol that combines advanced multi-modal imaging of the brain with clinical and behavioural scales to characterise the neural, behavioural, and clinical effects of transcranial direct current stimulation (tDCS) for rehabilitation in PDOC

Detailed Description

Patients with prolonged disorders of consciousness (PDOC) have very limited therapeutic options, and they often show little to no progress over time. Here, the investigators will assess whether transcranial direct current stimulation can improve patients' responsiveness. The investigators will use a protocol designed to target specific brain networks that have been shown to play a key role in explaining the lack of voluntary responses in PDOC. The study will focus on characterising the mechanisms of action of tDCS and the bases for potential individual differences in responsiveness to the stimulation across participants. This feasibility study is the first step towards developing personalised tDCS interventions to restore external responsiveness in PDOC patients. Its results will inform the design of a future trial fully powered for characterising neural, behavioural, and clinical effects of tDCS in PDOC as well as the mechanisms underlying individual differences in responsiveness.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
15
Inclusion Criteria
  • Aged 18 years or older
  • Receiving care at a recruitment site, with a consensus clinical diagnosis of PDOC from any aetiology (i.e. traumatic or non-traumatic injury).
  • Stable and with no need of mechanical support (i.e. respirator, etc.)
Exclusion Criteria
  • Scalp skin sores or any skin damage at the electrode sites
  • Metallic implants in the face or skull
  • Craniectomy or cranioplasty
  • No evidence of auditory startle in clinical observations, or absent brainstem auditory evoked potentials in recent clinical history (if data available)
  • MRI incompatible: metal plates incompatible with MRI scanners, pacemaker, inability to lay flat for prolonged periods of time, aneurysm clips, neurostimulators, brain/subdural electrodes, etc. (MRI stream ONLY)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
MRI streamTranscranial direct current stimulationIn this stream all patients receive 2 experimental interventions (anodal tDCS and cathodal tDCS) and a sham intervention (sham tDCS). These are delivered in randomised order, ensuring a balanced distribution of participants across possible orders. They will receive 5 sessions per condition (on consecutive days), for a total of 15 sessions. I. Anodal, cathodal, sham II. Anodal, sham, cathodal III. Cathodal, anodal, sham IV. Cathodal, sham, anodal V. Sham, anodal, cathodal VI. Sham, cathodal, anodal
Bedside streamTranscranial direct current stimulationIn this stream all patients receive 1 experimental interventions (either anodal tDCS or cathodal tDCS) and 1 sham intervention (sham tDCS). These include only 1 session per condition and are delivered in randomised order, resulting in the following possible combinations: I. Anodal, sham II. Cathodal, sham III. Sham, anodal IV. Sham, cathodal Participants will be randomly assigned to the above groups ensuring a balanced distribution of participants across them.
Primary Outcome Measures
NameTimeMethod
Retention at 6 months6 months after start of participation

percentage of participants on study at pre-specified time points counted from the start of participation in the study (i.e., first study procedure). This Outcome applies to the bedside stream only

Completionthrough completion of active phase of study (tDCS intervention), on average 4 weeks for bedside stream and 8 weeks for MRI stream

percentage of tDCS, MRI, and electrophysiology assessments completed per polarity

Retention at end of active phasethrough completion of active phase of study (tDCS intervention), on average 4 weeks for bedside stream and 8 weeks for MRI stream

percentage of participants on study at pre-specified time points counted from the start of participation in the study (i.e., first study procedure)

Retention at 3 months3 months after start of participation

percentage of participants on study at pre-specified time points counted from the start of participation in the study (i.e., first study procedure). This Outcome applies to the bedside stream only

Secondary Outcome Measures
NameTimeMethod
Structural MRIday 1 and day 5 of tDCS each polarity

This will include assessments of the gross macrostructure, and microstructure of brain tissue grey matter, white matter, and cerebrospinal fluid

EEG power in the alpha band in response to task instructionsdays 1 and 4 of each polarity in the MRI stream and day 1 of each polarity in the bedside stream

Envelope of bandpass filtered EEG data between 8-12 Hertz

Functional MRI in response to task instructionsday 1 and day 5 of tDCS each polarity

This will include assessments of the BOLD (blood oxygen level-dependent) response to characterise brain activity and connectivity during command following

EEG power in the beta band in response to task instructionsdays 1 and 4 of each polarity in the MRI stream and day 1 of each polarity in the bedside stream

Envelope of bandpass filtered EEG data between 13-30 Hertz

EMG (electromyography) amplitude changesdays 1-4 and day 2 of each polarity in the MRI and bedside streams respectively

Changes in the amplitude of the rectified EMG signal (high-pass filtered \> 50Hz) in response to instructions to move

Coma recovery scale -revisedregularly through active phase of study (baseline and outcome assessments), on average 4 weeks for bedside stream and 8 weeks for MRI stream

clinical diagnostic scale for disorders of consciousness. Total score ranges from 0 to 23, where higher scores mean a higher level of functioning and awareness

Glasgow Outcome Scale-extendedat 3 and 6 months after start of participation

Scale for functional outcome after brain injury. Total score ranges from 1 to 8, where higher values correspond to better outcome

Trial Locations

Locations (2)

Moseley Hall Hospital

🇬🇧

Birmingham, West Midlands, United Kingdom

The Wellington Hospital

🇬🇧

London, United Kingdom

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