Consciousness DisorderRAINDROPNCT04248946
Neural, Behavioural, and Clinical Effects of tDCS in PDOC; Feasibility Study
A study testing Transcranial direct current stimulation in people with Consciousness Disorder and Brain Injuries, run by University of Birmingham at 2 sites in United Kingdom.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Consciousness Disorder, Brain Injuries, Vegetative State
- What is being tested?
- Transcranial direct current stimulation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Jul 2021to Aug 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.)
Who cannot join
- 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)
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Moseley Hall Hospital
Birmingham, West Midlands, B13 8JL
The Wellington Hospital
London, NW8 9LE
Antonio Incisa, PhD CPsychol CSci, +44 (0)20 7483 5595, Antonio.Incisa@HCAHealthcare.co.uk
About this study
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
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
Read the 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.
- Being tested
- Transcranial direct current stimulation
- Medical subject headings
- Consciousness Disorders, Brain Injuries, Persistent Vegetative State
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial direct current stimulationOther
Also called tDCS
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
| Study group | Role | What they receive |
|---|---|---|
| MRI stream | Experimental | 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 Receives: Other: Transcranial direct current stimulation |
| Bedside stream | Experimental | 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. Receives: Other: Transcranial direct current stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: 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
Measured: 6 months after start of participation
Completion
percentage of tDCS, MRI, and electrophysiology assessments completed per polarity
Measured: through completion of active phase of study (tDCS intervention), on average 4 weeks for bedside stream and 8 weeks for MRI stream
Secondary outcomes (7)
Structural MRI
This will include assessments of the gross macrostructure, and microstructure of brain tissue grey matter, white matter, and cerebrospinal fluid
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: at 3 and 6 months after start of participation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2020
- Study startJul 2021 (estimated)
- Primary completionAug 2022 (estimated)
- Study completionAug 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Consciousness DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Wellington Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04248946
- Sponsor's protocol ID
- RG_18-269
- Acronym
- RAINDROP
- Status last verified
- Apr 2021
- First submitted
- 22 Jan 2020
- Last updated
- 3 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04248946
- Acronym / sponsor ID
- RAINDROP / RG_18-269
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Collaborators
- Wellington Hospital
- Study start
- Jul 2021 (estimated)
- Primary completion
- Aug 2022 (estimated)
- Study completion
- Aug 2022 (estimated)
- First posted
- 30 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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
| Arm | Type | Receives |
|---|---|---|
| MRI stream | Experimental | Other: Transcranial 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 stream | Experimental | Other: Transcranial 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.)
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial direct current stimulationAlso: tDCStDCS 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 | Bedside stream, MRI stream |
Primary outcome
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)
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
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
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
7 secondary outcomes
Structural MRI
Time frame: day 1 and day 5 of tDCS each polarity
Functional MRI in response to task instructions
Time frame: day 1 and day 5 of tDCS each polarity
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
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
EMG (electromyography) amplitude changes
Time frame: days 1-4 and day 2 of each polarity in the MRI and bedside streams respectively
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
Glasgow Outcome Scale-extended
Time frame: at 3 and 6 months after start of participation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial direct current stimulation in people with Consciousness Disorder and Brain Injuries, run by University of Birmingham at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Davinia Fernandez Espejo, PhD FHEA (01214145534, d.fernandez-espejo@bham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2021.