Traumatic Brain InjuryPhase 2NCT05616910
Inhaled Nitric Oxide for Microvascular Dysfunction in Traumatic Brain Injury
A Phase 2 study testing inhaled nitric oxide in people with Traumatic Brain Injury, run by University of Pennsylvania at 1 site in United States.
Trial summary
Traumatic brain injury (TBI) causes acute deficits in cerebral perfusion which may lead to secondary injury and worse outcomes. Inhaled nitric oxide (iNO) is a vasodilator that increases cerebral blood flow and is clinically used for hypoxic respiratory failure in neonates and adults. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- inhaled nitric oxide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Apr 2025to 28 Mar 2028
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18-75 (inclusive)
- GCS 9-12 or GCS 13-15 with an abnormal imaging scan
- Radiologic findings indicative of primarily diffuse TBI
Who cannot join
- Severe cardiac dysfunction (e.g. elevation of pulmonary edema on chest xray, large elevation of cardiac enzymes)
- Large focal injury (subdural hematoma, epidural hematoma, intraparenchymal hematoma, >30mL aggregate volume).
- Need for immediate neurosurgical intervention
- Pre-existing disabling psychiatric or neurological disorders such as cortical stroke, brain tumor, disabling multiple sclerosis, dementia, and severe TBI
- Known intracranial vessel disease
- Acute Respiratory Distress Syndrome (ARDS) or pre-existing pulmonary hypertension
Show all 11Show fewer
- Cardiopulmonary resuscitation or cardioversion at admission
- Chronic Kidney Disease (Glomerular Filtration Rate <60mL/min/1.73m2)
- Respiratory Infection
- Prisoners, patients in police custody, pregnant women
- Possible drug interactions (nitric oxide donors: prilocaine, sodium nitroprusside, nitroglycerin)
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
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, 19104
About this study
Traumatic brain injury (TBI) causes acute deficits in cerebral perfusion which may lead to secondary injury and worse outcomes. Inhaled nitric oxide (iNO) is a vasodilator that increases cerebral blood flow and is clinically used for hypoxic respiratory failure in neonates and adults. The investigators will perform a randomized controlled trial of iNO treatment in TBI patients acutely after injury. The investigators will then assess perfusion changes with optic neuromonitoring, blood biomarkers, and 6 month clinical outcomes.
Read the detailed description
The objective of this study is to show that inhaled nitric oxide can increase blood flow in the brain after traumatic brain injury, attenuating brain injury and resulting in improved long-term function.
The investigators will use optical brain monitoring to determine changes in cerebral perfusion and metabolism by iNO treatment in TBI subjects. Within 24 hours of enrollment, TBI subjects meeting the inclusion criteria without exclusion criteria will undergo 8 hour sessions of monitoring (4 hours on iNO, 4 hours on standard respiratory therapy) for 4 days. During this time, Noninvasive Neuro-optic Monitoring (NNOM) device will be placed on the scalp and cerebral perfusion and metabolism parameters will be monitored to assess for therapeutic effect of iNO. There will be within-subject comparison of cerebral perfusion and metabolism on and off iNO. Also, there will be within-group comparison of cerebral perfusion and metabolism on days when iNO is given first vs days when iNO is given at a second session. Additionally, these parameters from this group will compared to a parallel group of TBI patients receiving 8 hours of only standard respiratory therapy for 4 days.
The investigators will assess the safety profile of iNO use in TBI subjects. During the course of iNO therapy in the initial 4 days, study subjects will be monitored for methemoglobinemia, hypotension, renal failure, neurological exam changes, and any other adverse events. Additionally, the investigators will assess blood-based biomarkers of injury with blood draws at the end of each iNO treatment session in TBI subjects for 4 days. During the initial 4 days of the trial, blood draws will be performed at the end of each session to detect biomarkers. Specifically, biomarkers that have been shown to correlate with injury severity such as GFAP, NFL, UCHL-1, tau, and S100B will be monitored at the end of iNO session and standard respiratory therapy session. This will be performed by using a novel assay termed SIMOA, a sensitive detection method for blood-based biomarkers.
As an exploratory aim, the investigators will compare 6-month GOS-E outcomes and injury biomarkers of the patients who received iNO to those who received standard respiratory therapy. Patients will be assessed for their functional status at the time of 6 month follow up.
- Conditions
- Traumatic Brain Injury
- Being tested
- inhaled nitric oxide
- Keywords
- hypoperfusion, cerebral blood flow, nitric oxide, traumatic brain injury
- 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.
inhaled nitric oxideDrug
Also called standard respiratory therapy vs iNO
iNO will be provided by ventilator or nasal cannula for 4 hours each day.
| Study group | Role | What they receive |
|---|---|---|
| Group iNO | Experimental | Subjects will receive iNO for 4 hours, followed by standard respiratory support (SRS) for 4 hours. This pattern will be reversed the next day (SRS then iNO). on the following day, the pattern will be reversed back to iNO for 4 hours and SRS for 4 hrs. Receives: Drug: inhaled nitric oxide |
| Group SRS | Sham comparator | Subjects will receive standard respiratory support (SRS) for 8 hours. Receives: Drug: inhaled nitric oxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebral Metabolism assessed by Spectroscopy
Metabolic Rate of oxygen consumption by the brain measured by diffuse correlation spectroscopy and time-resolved infrared-spectroscopy.
Measured: 4 days
Secondary outcomes (5)
Incidence of Inhaled Nitric Oxide induced methemoglobinemia
Methemoglobin levels of blood greater than 1%
Measured: 4 days
Incidence of Inhaled Nitric Oxide induced hypotension
Blood pressure less than 90/60 mmHg for 30 minutes or longer
Measured: 4 days
Incidence of Inhaled Nitric Oxide induced neurological deterioration
Glasgow coma scale decrease of 2 or more points.
Measured: 4 days
Blood-based biomarkers of injury
Levels of neurofilament-light, glial fibrillary acidic protein, tau, ubiquitin carboxy-terminal hydrolase L1 (all biomarkers are in units of pg/mL)
Measured: 4 days, 6 months
Long term functional outcome
Glasgow Outcome Scale Extended (GOS-E) (range: 1-8, 1: death, 8: good recovery).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2022
- Study start6 Apr 2025
- Primary completion28 Mar 2028 (estimated)
- Study completion28 Mar 2028 (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 PennsylvaniaThe 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
- Masking
- None (open label)
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Samuel Shin, Principal investigator, Assistant Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05616910
- Sponsor's protocol ID
- 851809
- Status last verified
- Jun 2026
- First submitted
- 31 Oct 2022
- Last updated
- 17 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaled Nitric Oxide for Microvascular Dysfunction in Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT05616910
- Acronym / sponsor ID
- 851809
- Conditions
- Traumatic Brain Injury
- Keywords
- hypoperfusion, cerebral blood flow, nitric oxide, traumatic brain injury
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 38 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 6 Apr 2025 (actual)
- Primary completion
- 28 Mar 2028 (estimated)
- Study completion
- 28 Mar 2028 (estimated)
- First posted
- 15 Nov 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.
Traumatic brain injury (TBI) causes acute deficits in cerebral perfusion which may lead to secondary injury and worse outcomes. Inhaled nitric oxide (iNO) is a vasodilator that increases cerebral blood flow and is clinically used for hypoxic respiratory failure in neonates and adults. The investigators will perform a randomized controlled trial of iNO treatment in TBI patients acutely after injury. The investigators will then assess perfusion changes with optic neuromonitoring, blood biomarkers, and 6 month clinical outcomes.
Detailed description
The objective of this study is to show that inhaled nitric oxide can increase blood flow in the brain after traumatic brain injury, attenuating brain injury and resulting in improved long-term function.
The investigators will use optical brain monitoring to determine changes in cerebral perfusion and metabolism by iNO treatment in TBI subjects. Within 24 hours of enrollment, TBI subjects meeting the inclusion criteria without exclusion criteria will undergo 8 hour sessions of monitoring (4 hours on iNO, 4 hours on standard respiratory therapy) for 4 days. During this time, Noninvasive Neuro-optic Monitoring (NNOM) device will be placed on the scalp and cerebral perfusion and metabolism parameters will be monitored to assess for therapeutic effect of iNO. There will be within-subject comparison of cerebral perfusion and metabolism on and off iNO. Also, there will be within-group comparison of cerebral perfusion and metabolism on days when iNO is given first vs days when iNO is given at a second session. Additionally, these parameters from this group will compared to a parallel group of TBI patients receiving 8 hours of only standard respiratory therapy for 4 days.
The investigators will assess the safety profile of iNO use in TBI subjects. During the course of iNO therapy in the initial 4 days, study subjects will be monitored for methemoglobinemia, hypotension, renal failure, neurological exam changes, and any other adverse events. Additionally, the investigators will assess blood-based biomarkers of injury with blood draws at the end of each iNO treatment session in TBI subjects for 4 days. During the initial 4 days of the trial, blood draws will be performed at the end of each session to detect biomarkers. Specifically, biomarkers that have been shown to correlate with injury severity such as GFAP, NFL, UCHL-1, tau, and S100B will be monitored at the end of iNO session and standard respiratory therapy session. This will be performed by using a novel assay termed SIMOA, a sensitive detection method for blood-based biomarkers.
As an exploratory aim, the investigators will compare 6-month GOS-E outcomes and injury biomarkers of the patients who received iNO to those who received standard respiratory therapy. Patients will be assessed for their functional status at the time of 6 month follow up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group iNO | Experimental | Drug: inhaled nitric oxideSubjects will receive iNO for 4 hours, followed by standard respiratory support (SRS) for 4 hours. This pattern will be reversed the next day (SRS then iNO). on the following day, the pattern will be reversed back to iNO for 4 hours and SRS for 4 hrs. |
| Group SRS | Sham comparator | Drug: inhaled nitric oxideSubjects will receive standard respiratory support (SRS) for 8 hours. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Aged 18-75 (inclusive)
- GCS 9-12 or GCS 13-15 with an abnormal imaging scan
- Radiologic findings indicative of primarily diffuse TBI
Key exclusion criteria (11 listed)
- Severe cardiac dysfunction (e.g. elevation of pulmonary edema on chest xray, large elevation of cardiac enzymes)
- Large focal injury (subdural hematoma, epidural hematoma, intraparenchymal hematoma, >30mL aggregate volume).
- Need for immediate neurosurgical intervention
- Pre-existing disabling psychiatric or neurological disorders such as cortical stroke, brain tumor, disabling multiple sclerosis, dementia, and severe TBI
- Known intracranial vessel disease
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 |
|---|---|---|
| inhaled nitric oxideAlso: standard respiratory therapy vs iNOiNO will be provided by ventilator or nasal cannula for 4 hours each day. | Drug | Group SRS, Group iNO |
Primary outcome
Cerebral Metabolism assessed by Spectroscopy
Time frame: 4 days
Metabolic Rate of oxygen consumption by the brain measured by diffuse correlation spectroscopy and time-resolved infrared-spectroscopy.
5 secondary outcomes
Incidence of Inhaled Nitric Oxide induced methemoglobinemia
Time frame: 4 days
Incidence of Inhaled Nitric Oxide induced hypotension
Time frame: 4 days
Incidence of Inhaled Nitric Oxide induced neurological deterioration
Time frame: 4 days
Blood-based biomarkers of injury
Time frame: 4 days, 6 months
Long term functional outcome
Time frame: 6 months
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 17 Jun 2026.
- 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.
Samuel Shin principal investigator
Assistant Professor
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 inhaled nitric oxide in people with Traumatic Brain Injury, run by University of Pennsylvania 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 3 inclusion and 11 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: enrolling by invitation, as of the sponsor's last update on 17 Jun 2026. 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. Some participants in this study may receive a placebo. 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?
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?
Cerebral Metabolism assessed by Spectroscopy (time frame: 4 days). 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 17 Jun 2026.