Traumatic Brain InjuryPhase 2INDICTNCT05337618
Improving Neurotrauma by Depolarization Inhibition With Combination Therapy (INDICT)
A Phase 2 study testing Full-band Electrocorticography and Treatment Algorithm in people with Traumatic Brain Injury, run by University of Cincinnati at 1 site in United States.
Trial summary
This study is a randomized Phase 2 trial to determine the feasibility of real-time electrocorticographic monitoring of spreading depolarizations (SD) to guide implementation of a tier-based protocol of intensive care therapies, aimed at SD suppression, for the management of patients who have undergone acute operative… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Full-band Electrocorticography and Treatment Algorithm
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Dec 2022to 20 Mar 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- clinical indication for emergency craniotomy with dural opening to treat acute TBI within 72 hr post-trauma
Who cannot join
- persistent bilateral non-reactive pupils or other evidence of non-survivable injury,
- decompressive craniectomy to treat refractory ICP subsequent to diffuse injury, (3) co-enrollment in another therapeutic TBI trial, and
- pregnancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Cincinnati
Cincinnati, Ohio, 45267
Jed A Hartings, PhD, 513-295-2370, jed.hartings@uc.edu
About this study
Official title: Improving Neurotrauma by Depolarization Inhibition With Combination Therapy (INDICT): a Phase 2 Randomized, Feasibility Trial
This study is a randomized Phase 2 trial to determine the feasibility of real-time electrocorticographic monitoring of spreading depolarizations (SD) to guide implementation of a tier-based protocol of intensive care therapies, aimed at SD suppression, for the management of patients who have undergone acute operative treatment of severe traumatic brain injury.
Read the detailed description
The goal of acute TBI treatment is to minimize secondary damage that evolves over hours to days after the primary injury. Until now, however, there have been no methods for monitoring heterogeneous pathologic mechanisms to identify patients for appropriate neuroprotection therapies. Using invasive monitoring, investigators have documented that spreading depolarizations (SD), a cytotoxic dysfunction of cerebral gray matter that has been well-characterized through 60 years of research in animal models, are the dominant pathophysiologic process in peri-lesion cortex of many, but not all, severe TBI patients. Furthermore, it was found that the occurrence of SD as a secondary injury process in patients is an independent predictor of worse neurologic outcomes. Thus, monitoring of SD as a heterogeneous mechanism in TBI may allow selective use of therapy in only those patients who might benefit.
Here the investigators will conduct a randomized Phase 2 feasibility trial that uses real-time SD monitoring to guide implementation of a tier-based protocol of intensive care therapies aimed at SD suppression. The study is based on the hypothesis that outcomes from severe TBI can be improved by targeting intensive care therapies to suppress the pathology of SDs as a brain marker and mechanism of secondary injury. The objective of this study is to test the feasibility of this approach to intensive care management of severe TBI in a Phase 2 trial that uses real-time SD monitoring to guide administration of prescribed therapies to suppress SD. The aims are to (1) determine the feasibility of real-time SD monitoring to guide intensive care management of severe TBI, and (2) determine the effect of SD-guided vs. standard care management to reduce secondary brain insults in severe TBI.
This is a randomized Phase 2 clinical trial enrolling approximately 72 patients at 3 sites. Patients requiring neurological surgery for emergency treatment of TBI will be enrolled. The need for surgery allows for the placement of an electrode strip on the brain during surgery for subsequent electrocorticography (ECoG). ECoG data will be monitored continuously in real-time for the occurrence of SDs during intensive care. When SDs are observed, these patients (~60%, or n=43) will be randomized 1:1 to either standard (control) or SD-guided care. In the standard care arm, treatment will follow local and national guidelines with blinding to further ECoG results. In the SD-guided arm, treatment will follow a tiered-based protocol with escalation and de-escalation based on efficacy to suppress further SD pathology. Treatments will include use of ketamine sedation and adjusted targets for plasma glucose, cerebral perfusion pressure, temperature, and end-tidal CO2.
As outcomes, the accuracy of real-time SD scoring and compliance with protocol tier assignment and therapy implementation will be assessed. The burden of SD pathology, other measures of cerebral physiology (intracranial and cerebral perfusion pressures, and brain oxygenation), and medical complications will also be compared between the two study arms.
- Conditions
- Traumatic Brain Injury
- Being tested
- Full-band Electrocorticography, Treatment Algorithm
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Full-band ElectrocorticographyDiagnostic test
Diagnosis of spreading depolarizations in continuous electrocorticography
Treatment AlgorithmCombination product
Protocol for escalation and de-escalation of physiologic-targeted and pharmacologic therapies to treat and prevent spreading depolarizations
| Study group | Role | What they receive |
|---|---|---|
| SD-Guided Care | Experimental | In this arm, ECoG data will be reviewed for SDs in real-time using the bedside clinical CNS monitor. As a secondary measure, recognition of SDs will be facilitated by custom software on a laptop that receives data from the CNS monitor. Data on SD occurrence will be used to guide treatment in a tier-based therapeutic escalation and de-escalation protocol with the goal of SD suppression. Therapies to be used among the tiers include adjusted targets for MAP, CPP, PaCO2, plasma glucose, temperature, as well as ketamine pharmacotherapy. Changes between tiers are determined by the success or failure of SD suppression at the given treatment level. Receives: Diagnostic Test: Full-band Electrocorticography; Combination Product: Treatment Algorithm |
| Standard ICU Care | No intervention | Management in the Standard ICU Care arm will follow published national guidelines consisting of common ICU-based targets for physiologic intervention that are thought to mitigate the development of secondary brain injuries. Continuous ECoG monitoring will be performed for seizure monitoring, but information on the course of SDs in these patients will not be used to guide care. To enforce blinding to SD-related ECoG data, the ECoG bedside software will be locked with password protection to prevent displays with frequency filtering and time/amplitude scales that are necessary to identify SDs. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Burden of spreading depolarizations
Spreading depolarization events will be scored based on review of electrocorticographic recordings. The number of depolarizations per recording day over the period of monitoring will serve as the measure of total burden. The burdens computed for patients will be compared between the two randomization arms.
Measured: During the period of intensive care invasive monitoring, up to two weeks after injury
Secondary outcomes (4)
Burden of elevated intracranial pressure
The time integral of the continuously monitored intracranial pressure signal above 22 mmHg will be computed for each patient as the measure of burden. The burdens computed for patients will be compared between the two randomization arms.
Measured: During the period of intensive care invasive monitoring, up to two weeks after injury
Burden of cerebral hypoxia
The time integral of the continuously monitored cerebral oxygenation below 20 mmHg will be computed for each patient as the measure of burden. The burdens computed for patients will be compared between the two randomization arms.
Measured: During the period of intensive care invasive monitoring, up to two weeks after injury
Burden of low cerebral perfusion
The time integral of the continuously monitored cerebral perfusions pressure below 60 mmHg will be computed for each patient as the measure of burden. The burdens computed for patients will be compared between the two randomization arms.
Measured: During the period of intensive care invasive monitoring, up to two weeks after injury
Glasgow Outcome Score-Extended
Scores on the GOS-E will be compared between the two randomization arms
Measured: 6 months post-injury
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2022
- Study start16 Dec 2022
- Primary completion1 Sep 2026 (estimated)
- Study completion20 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized to one of two study groups based on a block design with randomized block sizes of 2, 4 or 6 determined individually for each study site.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- University of New Mexico, University of Pennsylvania
- Responsible party
- Principal investigator, Jed Hartings, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05337618
- Sponsor's protocol ID
- Not yet assigned
- Acronym
- INDICT
- Status last verified
- Dec 2025
- First submitted
- 5 Apr 2022
- Last updated
- 22 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). Data will also be shared through the Federal Interagency Traumatic Brain Injury Registry (FITBIR).
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Neurotrauma by Depolarization Inhibition With Combination Therapy (INDICT): a Phase 2 Randomized, Feasibility Trial
- ClinicalTrials.gov ID
- NCT05337618
- Acronym / sponsor ID
- INDICT / Not yet assigned
- Conditions
- Traumatic Brain Injury
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- University of New Mexico, University of Pennsylvania
- Study start
- 16 Dec 2022 (actual)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 20 Mar 2027 (estimated)
- First posted
- 20 Apr 2022 (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 is a randomized Phase 2 trial to determine the feasibility of real-time electrocorticographic monitoring of spreading depolarizations (SD) to guide implementation of a tier-based protocol of intensive care therapies, aimed at SD suppression, for the management of patients who have undergone acute operative treatment of severe traumatic brain injury.
Detailed description
The goal of acute TBI treatment is to minimize secondary damage that evolves over hours to days after the primary injury. Until now, however, there have been no methods for monitoring heterogeneous pathologic mechanisms to identify patients for appropriate neuroprotection therapies. Using invasive monitoring, investigators have documented that spreading depolarizations (SD), a cytotoxic dysfunction of cerebral gray matter that has been well-characterized through 60 years of research in animal models, are the dominant pathophysiologic process in peri-lesion cortex of many, but not all, severe TBI patients. Furthermore, it was found that the occurrence of SD as a secondary injury process in patients is an independent predictor of worse neurologic outcomes. Thus, monitoring of SD as a heterogeneous mechanism in TBI may allow selective use of therapy in only those patients who might benefit.
Here the investigators will conduct a randomized Phase 2 feasibility trial that uses real-time SD monitoring to guide implementation of a tier-based protocol of intensive care therapies aimed at SD suppression. The study is based on the hypothesis that outcomes from severe TBI can be improved by targeting intensive care therapies to suppress the pathology of SDs as a brain marker and mechanism of secondary injury. The objective of this study is to test the feasibility of this approach to intensive care management of severe TBI in a Phase 2 trial that uses real-time SD monitoring to guide administration of prescribed therapies to suppress SD. The aims are to (1) determine the feasibility of real-time SD monitoring to guide intensive care management of severe TBI, and (2) determine the effect of SD-guided vs. standard care management to reduce secondary brain insults in severe TBI.
This is a randomized Phase 2 clinical trial enrolling approximately 72 patients at 3 sites. Patients requiring neurological surgery for emergency treatment of TBI will be enrolled. The need for surgery allows for the placement of an electrode strip on the brain during surgery for subsequent electrocorticography (ECoG). ECoG data will be monitored continuously in real-time for the occurrence of SDs during intensive care. When SDs are observed, these patients (~60%, or n=43) will be randomized 1:1 to either standard (control) or SD-guided care. In the standard care arm, treatment will follow local and national guidelines with blinding to further ECoG results. In the SD-guided arm, treatment will follow a tiered-based protocol with escalation and de-escalation based on efficacy to suppress further SD pathology. Treatments will include use of ketamine sedation and adjusted targets for plasma glucose, cerebral perfusion pressure, temperature, and end-tidal CO2.
As outcomes, the accuracy of real-time SD scoring and compliance with protocol tier assignment and therapy implementation will be assessed. The burden of SD pathology, other measures of cerebral physiology (intracranial and cerebral perfusion pressures, and brain oxygenation), and medical complications will also be compared between the two study arms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomized to one of two study groups based on a block design with randomized block sizes of 2, 4 or 6 determined individually for each study site.
| Arm | Type | Receives |
|---|---|---|
| SD-Guided Care | Experimental | Diagnostic Test: Full-band Electrocorticography, Combination Product: Treatment AlgorithmIn this arm, ECoG data will be reviewed for SDs in real-time using the bedside clinical CNS monitor. As a secondary measure, recognition of SDs will be facilitated by custom software on a laptop that receives data from the CNS monitor. Data on SD occurrence will be used to guide treatment in a tier-based therapeutic escalation and de-escalation protocol with the goal of SD suppression. Therapies to be used among the tiers include adjusted targets for MAP, CPP, PaCO2, plasma glucose, temperature, as well as ketamine pharmacotherapy. Changes between tiers are determined by the success or failure of SD suppression at the given treatment level. |
| Standard ICU Care | No intervention | –Management in the Standard ICU Care arm will follow published national guidelines consisting of common ICU-based targets for physiologic intervention that are thought to mitigate the development of secondary brain injuries. Continuous ECoG monitoring will be performed for seizure monitoring, but information on the course of SDs in these patients will not be used to guide care. To enforce blinding to SD-related ECoG data, the ECoG bedside software will be locked with password protection to prevent displays with frequency filtering and time/amplitude scales that are necessary to identify SDs. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- clinical indication for emergency craniotomy with dural opening to treat acute TBI within 72 hr post-trauma
Key exclusion criteria (3 listed)
- persistent bilateral non-reactive pupils or other evidence of non-survivable injury,
- decompressive craniectomy to treat refractory ICP subsequent to diffuse injury, (3) co-enrollment in another therapeutic TBI trial, and
- pregnancy
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 |
|---|---|---|
| Full-band ElectrocorticographyDiagnosis of spreading depolarizations in continuous electrocorticography | Diagnostic test | SD-Guided Care |
| Treatment AlgorithmProtocol for escalation and de-escalation of physiologic-targeted and pharmacologic therapies to treat and prevent spreading depolarizations | Combination product | SD-Guided Care |
Primary outcome
Burden of spreading depolarizations
Time frame: During the period of intensive care invasive monitoring, up to two weeks after injury
Spreading depolarization events will be scored based on review of electrocorticographic recordings. The number of depolarizations per recording day over the period of monitoring will serve as the measure of total burden. The burdens computed for patients will be compared between the two randomization arms.
4 secondary outcomes
Burden of elevated intracranial pressure
Time frame: During the period of intensive care invasive monitoring, up to two weeks after injury
Burden of cerebral hypoxia
Time frame: During the period of intensive care invasive monitoring, up to two weeks after injury
Burden of low cerebral perfusion
Time frame: During the period of intensive care invasive monitoring, up to two weeks after injury
Glasgow Outcome Score-Extended
Time frame: 6 months post-injury
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2025.
- Individual participant dataSharing planned: Yes. Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). Data will also be shared through the Federal Interagency Traumatic Brain Injury Registry (FITBIR).
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Full-band Electrocorticography and Treatment Algorithm in people with Traumatic Brain Injury, run by University of Cincinnati at 1 site in United States.
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 1 inclusion and 3 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: looking for participants now, as of the sponsor's last update on 22 Dec 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 United States. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jed A Hartings, PhD (513-295-2370, jed.hartings@uc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Burden of spreading depolarizations (time frame: During the period of intensive care invasive monitoring, up to two weeks after injury). 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 22 Dec 2025.