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

• ClinicalTrials.gov Identifier: NCT04248946
• Recruitment Status: Not yet recruiting
• First Posted: January 30, 2020
• Last Update Posted: May 3, 2021
• Sponsor: University of Birmingham
• Collaborator: Wellington Hospital
• Information provided by (Responsible Party): University of Birmingham

Study Description

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

Condition or disease	Intervention/treatment	Phase
Consciousness Disorder; Brain Injuries; Vegetative State; Minimally Conscious State	Other: Transcranial direct current stimulation	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: This is a double-blind randomised crossover feasibility study of tDCS in a small cohort of PDOC individuals. The study is divided into two streams to accommodate differences in the resources available across recruitment sites: 1. MRI stream, which will include MRI and electrophysiology assessments; this is available to patients receiving care at the Wellington Hospital in London only. 2. Bedside stream, which will include electrophysiology assessments only, available to patients in specialist units at NHS (National Health Service) and non-NHS sites
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: In the MRI stream all participants will receive anodal, cathodal, and sham (placebo) tDCS sessions in a randomised order. In the Bedside stream participants will receive active tDCS (either anodal or cathodal) and sham sessions also in a randomised order. A researcher not involved in data collection or analyses will programme the stimulator to deliver the specific polarity needed in each session in a double-blind manner. Sham tDCS will be delivered according to published guidelines: this mimics the physical sensations of active stimulation but does not have a neuromodulatory effect
• Primary Purpose: Basic Science
• Official Title: 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
• Estimated Study Start Date: July 2021
• Estimated Primary Completion Date: August 2022
• Estimated Study Completion Date: August 2022

Arms and Interventions

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 Name: 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 Name: tDCS

Outcome Measures

Primary Outcome Measures :

1. Retention at end of active phase [ Time Frame: through 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)
2. Retention at 3 months [ Time Frame: 3 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
3. Retention at 6 months [ Time Frame: 6 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
4. Completion [ Time Frame: through 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

Secondary Outcome Measures :

1. Structural MRI [ Time Frame: day 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
2. Functional MRI in response to task instructions [ Time Frame: day 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
3. EEG power in the alpha band in response to task instructions [ Time Frame: days 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
4. EEG power in the beta band in response to task instructions [ Time Frame: days 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
5. EMG (electromyography) amplitude changes [ Time Frame: days 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
6. Coma recovery scale -revised [ Time Frame: regularly 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
7. Glasgow Outcome Scale-extended [ Time Frame: at 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Contacts

Contact: Davinia Fernandez Espejo, PhD FHEA; 01214145534; d.fernandez-espejo@bham.ac.uk

Locations

United Kingdom

Moseley Hall Hospital

Birmingham, West Midlands, United Kingdom, B13 8JL

The Wellington Hospital

London, United Kingdom, NW8 9LE

Contact: Antonio Incisa, PhD CPsychol CSci +44 (0)20 7483 5595 Antonio.Incisa@HCAHealthcare.co.uk

Sponsors and Collaborators

University of Birmingham

Wellington Hospital

More Information

• Responsible Party: University of Birmingham
• ClinicalTrials.gov Identifier: NCT04248946
• Other Study ID Numbers: RG_18-269
• First Posted: January 30, 2020
• Last Update Posted: May 3, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Brain Injuries; Persistent Vegetative State; Consciousness Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Brain Damage, Chronic; Unconsciousness; Neurobehavioral Manifestations; Neurologic Manifestations; Neurocognitive Disorders; Mental Disorders