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

Sham-controlled, Double-blind, Randomised Crossover Study of the Neural, Behavioural, and Clinical Effects of Transcranial Direct Current Stimulation in Patients With a Prolonged Disorder of Consciousness; Feasibility Study

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

Study Overview

• Status: Not yet recruiting
• Conditions: Brain Injuries; Minimally Conscious State; Vegetative State; Consciousness Disorder
• Intervention / Treatment: Other: Transcranial direct current stimulation

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.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Davinia Fernandez Espejo, PhD FHEA; Phone Number: 01214145534; Email: d.fernandez-espejo@bham.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, NW8 9LE
    • The Wellington Hospital
    • Contact: Antonio Incisa, PhD CPsychol CSci; Phone Number: +44 (0)20 7483 5595; Email: Antonio.Incisa@HCAHealthcare.co.uk
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B13 8JL
      • Moseley Hall Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MRI stream; In 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	Other: Transcranial direct current stimulation; tDCS alters neural excitability in a polarity-specific manner via a weak direct electric current delivered through electrodes placed on the scalp. There are 3 types of stimulation: anodal, cathodal, and sham. In anodal tDCS, the positive electrode is placed over the target brain area to increase neuronal excitability. In cathodal tDCS, the negative electrode is placed over the target brain area to decrease neuronal excitability. Sham tDCS emulates the physical sensations of active (anodal/cathodal) tDCS but current is only delivered for a short period of time and is not enough to cause any neuromodulations; Other Names: tDCS
EXPERIMENTAL: Bedside stream; In 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.	Other: Transcranial direct current stimulation; tDCS alters neural excitability in a polarity-specific manner via a weak direct electric current delivered through electrodes placed on the scalp. There are 3 types of stimulation: anodal, cathodal, and sham. In anodal tDCS, the positive electrode is placed over the target brain area to increase neuronal excitability. In cathodal tDCS, the negative electrode is placed over the target brain area to decrease neuronal excitability. Sham tDCS emulates the physical sensations of active (anodal/cathodal) tDCS but current is only delivered for a short period of time and is not enough to cause any neuromodulations; Other Names: tDCS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retention at end of active phase	percentage of participants on study at pre-specified time points counted from the start of participation in the study (i.e., first study procedure)	through completion of active phase of study (tDCS intervention), on average 4 weeks for bedside stream and 8 weeks for MRI stream
Retention at 3 months	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	3 months after start of participation
Retention at 6 months	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	6 months after start of participation
Completion	percentage of tDCS, MRI, and electrophysiology assessments completed per polarity	through completion of active phase of study (tDCS intervention), on average 4 weeks for bedside stream and 8 weeks for MRI stream

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Structural MRI	This will include assessments of the gross macrostructure, and microstructure of brain tissue grey matter, white matter, and cerebrospinal fluid	day 1 and day 5 of tDCS each polarity
Functional MRI in response to task instructions	This will include assessments of the BOLD (blood oxygen level-dependent) response to characterise brain activity and connectivity during command following	day 1 and day 5 of tDCS each polarity
EEG power in the alpha band in response to task instructions	Envelope of bandpass filtered EEG data between 8-12 Hertz	days 1 and 4 of each polarity in the MRI stream and day 1 of each polarity in the bedside stream
EEG power in the beta band in response to task instructions	Envelope of bandpass filtered EEG data between 13-30 Hertz	days 1 and 4 of each polarity in the MRI stream and day 1 of each polarity in the bedside stream
EMG (electromyography) amplitude changes	Changes in the amplitude of the rectified EMG signal (high-pass filtered > 50Hz) in response to instructions to move	days 1-4 and day 2 of each polarity in the MRI and bedside streams respectively
Coma recovery scale -revised	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	regularly through active phase of study (baseline and outcome assessments), on average 4 weeks for bedside stream and 8 weeks for MRI stream
Glasgow Outcome Scale-extended	Scale for functional outcome after brain injury. Total score ranges from 1 to 8, where higher values correspond to better outcome	at 3 and 6 months after start of participation

Collaborators and Investigators

• Sponsor: University of Birmingham
• Collaborators: Wellington Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2021
• Primary Completion (ANTICIPATED): August 1, 2022
• Study Completion (ANTICIPATED): August 1, 2022

Study Registration Dates

• First Submitted: January 22, 2020
• First Submitted That Met QC Criteria: January 28, 2020
• First Posted (ACTUAL): January 30, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 30, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Neurobehavioral Manifestations; Neurocognitive Disorders; Brain Damage, Chronic; Craniocerebral Trauma; Trauma, Nervous System; Unconsciousness; Brain Injuries; Consciousness Disorders; Persistent Vegetative State
• Other Study ID Numbers: RG_18-269

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No