Disorders of Consciousness Due to Severe Brain InjuryMICRO-DOCNCT06845800
Peripheral Nerve Stimulation for Prognostic and Diagnostic Biomarker Identification in Disorders of Consciousness
An observational study of Disorders of Consciousness Due to Severe Brain Injury, run by Fondazione Don Carlo Gnocchi ETS at 1 site in Italy.
Trial summary
This observational study aims to integrate anamnestic, clinical, and innovative neurophysiological data to assess their impact on the diagnosis and prognosis of patients with Disorders of Consciousness. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Disorders of Consciousness Due to Severe Brain Injury
- How many people
- 28 participants
- Where
- 1 siteItaly
- Study dates
- 21 Jul 2022to 28 Mar 2025
- How long will I take part?
- 2 Months
- Phase
- Observational
- 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
Study population: Patients who were admitted with a Disorder of Consciousness to the Intensive Rehabilitation Unit (IRU) of Fondazione Don Carlo Gnocchi (Florence).
Who may be able to join
- Age > 18 years, both sexes;
- Severe acquired brain injury (regardless of etiology);
- Patients with severe alteration of consciousness state due to severe acquired brain injury of various etiologies (Cardiac Arrest, Traumatic Brain Injury, Cerebral Ischemia or Hemorrhage);
- Informed consent signature by family member/caregiver/legal guardian.
Who cannot join
- Time since the acute event greater than 3 months;
- Previous neurological diseases;
- Previous acute brain injuries, psychiatric disorders, neurodegenerative diseases, neoplasms, severe systemic diseases;
- Modified Barthel Index pre-event < 50;
- Unstable medical conditions.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Microneurography and Microneurostimulation for Prognosis and Rehabilitation of Disorders of Consciousness
This observational study aims to integrate anamnestic, clinical, and innovative neurophysiological data to assess their impact on the diagnosis and prognosis of patients with Disorders of Consciousness. The main questions it aims to answer are:
- Is it possible to identify biomarkers with high diagnostic relevance for distinguishing subcategories of patients with Disorders of Consciousness?
- Can biomarkers with potential medium- and long-term prognostic value be identified for each category of patients with Disorders of Consciousness?
Participants will undergo an EEG examination during near-nerve stimulation of the median nerve. Clinical and anamnestic data will also be recorded and collected at follow-up.
Read the detailed description
At the enrollment of each patient with Disorders of Consciousness, demographic, anamnestic, and clinical data are prospectively collected. The etiology is categorized as traumatic, anoxic, hemorrhagic, or ischemic. The lesion side is defined according to the latest CT scans from the acute phase and is grouped as left, right, and bilateral. All patients undergo a standard neurophysiological evaluation, and the level of consciousness is assessed using the CRS-R scale following international guidelines. It is repeated to confirm the clinical status of the patient, and a reduction of sedation is performed if deemed safe by the physician. Two months after admission to the IRU, the neurophysiological and consciousness assessments are repeated.
In addition to clinical and standard neurophysiological evaluations, two types of SSEPs are acquired during continuous EEG recording through both Surface Cutaneous Stimulation (SCS) and Near-Nerve Stimulation (NNS) of the median nerve. EEG signals are collected using a 61-channel cap with a sampling rate of 512 Hz.
The electrical stimulation is applied over the median nerve proximally to the wrist, and the stimulation side is chosen contralaterally to the less affected hemisphere. Superficial bipolar electrodes are used for SCS, whereas a microneedle with 1 MΩ of impedance is inserted under the skin for NNS. The electrical pulse of 0.2 ms is delivered at a rate of 1 Hz in two sets of 50 repetitions. The stimulation amplitude is chosen as the minimum value able to generate a response only in sensory or sensory-motor fibers for NNS and SCS, respectively. The only sensory activation in NNS is preferred to minimize the influence of motor twitches on brain responses. For SCS, due to the difficulty of exclusively stimulating sensory fibers, the amplitude is set as the minimal value required to elicit both sensory and motor activation.
To monitor the stimulated fibers, the peripheral pathway of the median nerve is recorded. In particular, surface electrodes are positioned on the three fingers innervated by the median nerve for the acquisition of Sensory Nerve Action Potential (SNAP) and on the palm proximally to the motor twitch for the acquisition of Compound Motor Action Potential (CMAP). This information is essential in patients with DoC for different reasons:
- Identifying the proximity to the median nerve, a crucial step due to the unresponsiveness and lack of cooperation of this population.ii) Identifying the type of active fibers.iii) Monitoring feedback to confirm the accurate placement of the microelectrode.
Whenever the minimum amplitude evokes a CMAP/SNAP, the related amplitude is selected for SCS/NNS. The device automatically extracts the mean values of amplitude and latency of CMAP/SNAP during the experimental session.
- Keywords
- Electroencephalography, Near-Nerve Stimulation, Prognosis, Diagnosis, Neurorehabilitation, Disorder of Consciousness
- Medical subject headings
- Disease, Consciousness Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with Disorders of Consciousness admitted to the Intensive Rehabilitation Unit | Patients admitted with a Disorder of Consciousness to the Intensive Rehabilitation Unit (IRU) of Fondazione Don Carlo Gnocchi (Florence). * Age ≥ 18 years, both sexes; * Severe Acquired Brain Injury (ABI), regardless of etiology; * Patients with a severe alteration of consciousness due to severe ABI of various etiologies, including Cardiac Arrest, Traumatic Brain Injury, Cerebral Ischemia, or Hemorrhage; * Signed informed consent provided by a family member, caregiver, or legal guardian. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of Neurophysiological Diagnostic Biomarkers in Disorders of Consciousness
Quantification of the Agreement Between Newly Proposed Neurophysiological Markers From Near-Nerve Stimulation Examinations and Disorders of Consciousness Classification Based on the Coma Recovery Scale-Revised (UWS, MCS-, MCS+)
Measured: From enrollment to the baseline experimental session (within 7 days from enrollment)
Identification of Neurophysiological Prognostic Biomarkers in Disorders of Consciousness
Quantification of Prognostic Prediction Accuracy of Newly Proposed Neurophysiological Markers From Near-Nerve Stimulation in Classifying Disorders of Consciousness Based on the Coma Recovery Scale - Revised (UWS, MCS-, MCS+, EMCS)
Measured: From enrollment to the end of follow up at 6-months from baseline assessment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2025
- Study start21 Jul 2022
- Primary completion28 Mar 2025
- Study completion28 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Disorders of Consciousness Due to Severe Brain InjuryStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 28 participants (actual)
- Target duration
- 2 Months
Sponsor and investigators
- Lead sponsor
- Fondazione Don Carlo Gnocchi ETS
- Sponsor type
- University, hospital or other
- Collaborators
- Scuola Superiore Sant'Anna Pisa
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06845800
- Sponsor's protocol ID
- TUNEBEAM_MICRODOC
- Acronym
- MICRO-DOC
- Status last verified
- Feb 2025
- First submitted
- 17 Feb 2025
- Last updated
- 24 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Upon publication of results, anonymized data and analysis code will be shared to ensure reproducibility. Zenodo and GitHub repositories will be created.
Publications
Vallbo AB. Microneurography: how it started and how it works. J Neurophysiol. 2018 Sep 1;120(3):1415-1427. doi: 10.1152/jn.00933.2017. Epub 2018 Jun 20.
PubMed 29924706Mano T, Iwase S, Toma S. Microneurography as a tool in clinical neurophysiology to investigate peripheral neural traffic in humans. Clin Neurophysiol. 2006 Nov;117(11):2357-84. doi: 10.1016/j.clinph.2006.06.002. Epub 2006 Aug 10.
PubMed 16904937Hakiki B, Donnini I, Romoli AM, Draghi F, Maccanti D, Grippo A, Scarpino M, Maiorelli A, Sterpu R, Atzori T, Mannini A, Campagnini S, Bagnoli S, Ingannato A, Nacmias B, De Bellis F, Estraneo A, Carli V, Pasqualone E, Comanducci A, Navarro J, Carrozza MC, Macchi C, Cecchi F. Clinical, Neurophysiological, and Genetic Predictors of Recovery in Patients With Severe Acquired Brain Injuries (PRABI): A Study Protocol for a Longitudinal Observational Study. Front Neurol. 2022 Feb 28;13:711312. doi: 10.3389/fneur.2022.711312. eCollection 2022.
PubMed 35295839
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microneurography and Microneurostimulation for Prognosis and Rehabilitation of Disorders of Consciousness
- ClinicalTrials.gov ID
- NCT06845800
- Acronym / sponsor ID
- MICRO-DOC / TUNEBEAM_MICRODOC
- Keywords
- Electroencephalography, Near-Nerve Stimulation, Prognosis, Diagnosis, Neurorehabilitation, Disorder of Consciousness
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Fondazione Don Carlo Gnocchi ETSUniversity, hospital or other
- Collaborators
- Scuola Superiore Sant'Anna Pisa
- Study start
- 21 Jul 2022 (actual)
- Primary completion
- 28 Mar 2025 (actual)
- Study completion
- 28 Mar 2025 (actual)
- First posted
- 25 Feb 2025 (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 observational study aims to integrate anamnestic, clinical, and innovative neurophysiological data to assess their impact on the diagnosis and prognosis of patients with Disorders of Consciousness. The main questions it aims to answer are:
- Is it possible to identify biomarkers with high diagnostic relevance for distinguishing subcategories of patients with Disorders of Consciousness?
- Can biomarkers with potential medium- and long-term prognostic value be identified for each category of patients with Disorders of Consciousness?
Participants will undergo an EEG examination during near-nerve stimulation of the median nerve. Clinical and anamnestic data will also be recorded and collected at follow-up.
Detailed description
At the enrollment of each patient with Disorders of Consciousness, demographic, anamnestic, and clinical data are prospectively collected. The etiology is categorized as traumatic, anoxic, hemorrhagic, or ischemic. The lesion side is defined according to the latest CT scans from the acute phase and is grouped as left, right, and bilateral. All patients undergo a standard neurophysiological evaluation, and the level of consciousness is assessed using the CRS-R scale following international guidelines. It is repeated to confirm the clinical status of the patient, and a reduction of sedation is performed if deemed safe by the physician. Two months after admission to the IRU, the neurophysiological and consciousness assessments are repeated.
In addition to clinical and standard neurophysiological evaluations, two types of SSEPs are acquired during continuous EEG recording through both Surface Cutaneous Stimulation (SCS) and Near-Nerve Stimulation (NNS) of the median nerve. EEG signals are collected using a 61-channel cap with a sampling rate of 512 Hz.
The electrical stimulation is applied over the median nerve proximally to the wrist, and the stimulation side is chosen contralaterally to the less affected hemisphere. Superficial bipolar electrodes are used for SCS, whereas a microneedle with 1 MΩ of impedance is inserted under the skin for NNS. The electrical pulse of 0.2 ms is delivered at a rate of 1 Hz in two sets of 50 repetitions. The stimulation amplitude is chosen as the minimum value able to generate a response only in sensory or sensory-motor fibers for NNS and SCS, respectively. The only sensory activation in NNS is preferred to minimize the influence of motor twitches on brain responses. For SCS, due to the difficulty of exclusively stimulating sensory fibers, the amplitude is set as the minimal value required to elicit both sensory and motor activation.
To monitor the stimulated fibers, the peripheral pathway of the median nerve is recorded. In particular, surface electrodes are positioned on the three fingers innervated by the median nerve for the acquisition of Sensory Nerve Action Potential (SNAP) and on the palm proximally to the motor twitch for the acquisition of Compound Motor Action Potential (CMAP). This information is essential in patients with DoC for different reasons:
- Identifying the proximity to the median nerve, a crucial step due to the unresponsiveness and lack of cooperation of this population.ii) Identifying the type of active fibers.iii) Monitoring feedback to confirm the accurate placement of the microelectrode.
Whenever the minimum amplitude evokes a CMAP/SNAP, the related amplitude is selected for SCS/NNS. The device automatically extracts the mean values of amplitude and latency of CMAP/SNAP during the experimental session.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Months
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with Disorders of Consciousness admitted to the Intensive Rehabilitation Unit | – | –Patients admitted with a Disorder of Consciousness to the Intensive Rehabilitation Unit (IRU) of Fondazione Don Carlo Gnocchi (Florence). * Age ≥ 18 years, both sexes; * Severe Acquired Brain Injury (ABI), regardless of etiology; * Patients with a severe alteration of consciousness due to severe ABI of various etiologies, including Cardiac Arrest, Traumatic Brain Injury, Cerebral Ischemia, or Hemorrhage; * Signed informed consent provided by a family member, caregiver, or legal guardian. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who were admitted with a Disorder of Consciousness to the Intensive Rehabilitation Unit (IRU) of Fondazione Don Carlo Gnocchi (Florence).
Key inclusion criteria (4 listed)
- Age > 18 years, both sexes;
- Severe acquired brain injury (regardless of etiology);
- Patients with severe alteration of consciousness state due to severe acquired brain injury of various etiologies (Cardiac Arrest, Traumatic Brain Injury, Cerebral Ischemia or Hemorrhage);
- Informed consent signature by family member/caregiver/legal guardian.
Key exclusion criteria (5 listed)
- Time since the acute event greater than 3 months;
- Previous neurological diseases;
- Previous acute brain injuries, psychiatric disorders, neurodegenerative diseases, neoplasms, severe systemic diseases;
- Modified Barthel Index pre-event < 50;
- Unstable medical conditions.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Identification of Neurophysiological Diagnostic Biomarkers in Disorders of Consciousness
Time frame: From enrollment to the baseline experimental session (within 7 days from enrollment)
Quantification of the Agreement Between Newly Proposed Neurophysiological Markers From Near-Nerve Stimulation Examinations and Disorders of Consciousness Classification Based on the Coma Recovery Scale-Revised (UWS, MCS-, MCS+)
Identification of Neurophysiological Prognostic Biomarkers in Disorders of Consciousness
Time frame: From enrollment to the end of follow up at 6-months from baseline assessment
Quantification of Prognostic Prediction Accuracy of Newly Proposed Neurophysiological Markers From Near-Nerve Stimulation in Classifying Disorders of Consciousness Based on the Coma Recovery Scale - Revised (UWS, MCS-, MCS+, EMCS)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2025.
- Background: PubMed 29924706Vallbo AB. Microneurography: how it started and how it works. J Neurophysiol. 2018 Sep 1;120(3):1415-1427. doi: 10.1152/jn.00933.2017. Epub 2018 Jun 20.
- Background: PubMed 16904937Mano T, Iwase S, Toma S. Microneurography as a tool in clinical neurophysiology to investigate peripheral neural traffic in humans. Clin Neurophysiol. 2006 Nov;117(11):2357-84. doi: 10.1016/j.clinph.2006.06.002. Epub 2006 Aug 10.
- Background: PubMed 35295839Hakiki B, Donnini I, Romoli AM, Draghi F, Maccanti D, Grippo A, Scarpino M, Maiorelli A, Sterpu R, Atzori T, Mannini A, Campagnini S, Bagnoli S, Ingannato A, Nacmias B, De Bellis F, Estraneo A, Carli V, Pasqualone E, Comanducci A, Navarro J, Carrozza MC, Macchi C, Cecchi F. Clinical, Neurophysiological, and Genetic Predictors of Recovery in Patients With Severe Acquired Brain Injuries (PRABI): A Study Protocol for a Longitudinal Observational Study. Front Neurol. 2022 Feb 28;13:711312. doi: 10.3389/fneur.2022.711312. eCollection 2022.
- Individual participant dataSharing planned: Yes. Upon publication of results, anonymized data and analysis code will be shared to ensure reproducibility. Zenodo and GitHub repositories will be created.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Disorders of Consciousness Due to Severe Brain Injury, run by Fondazione Don Carlo Gnocchi ETS at 1 site in Italy.
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 4 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: finished, as of the sponsor's last update on 24 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of Neurophysiological Diagnostic Biomarkers in Disorders of Consciousness (time frame: From enrollment to the baseline experimental session (within 7 days from enrollment)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06845800, which also lists 3 linked publications.
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 24 Aug 2025.