Traumatic Brain InjuryNNOMNCT02983786
Detection of Cerebral Ischemia With a Noninvasive Neurometabolic Optical Monitor
An observational study of Traumatic Brain Injury and Ischemic Stroke, run by University of Pennsylvania at 1 site in United States.
Trial summary
The goals of the project are to evaluate a noninvasive monitor of brain metabolism and blood flow in critically ill humans. If validated, such a reliable noninvasive brain blood flow and metabolism monitor, by allowing physiologic and pharmacologic decisions based on real-time brain physiology, potentially will become… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Traumatic Brain Injury, Ischemic Stroke, Intracerebral Hemorrhage
- What is being tested?
- Indocyanine Green
- Type of treatment
- Injection or infusion
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2015to 25 May 2022
- 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: Inclusion criteria will be age greater than or equal to 18 years, the diagnosis of SAH, TBI, ICH, and/or PIAE after cardiac arrest (post cardiac arrest coma) with GCS less than or equal to 8 (coma- clinical indications for invasive neuromonitoring), endotracheal intubation, clinical indications for invasive neuromonitoring, and family/guardian informed consent.
Who may be able to join
- Inclusion criteria will be age greater than or equal to 18 years, the diagnosis of SAH, TBI, ICH, and/or (PIAE) after cardiac arrest (post cardiac arrest coma) with GCS less than or equal to 8, endotracheal intubation, clinical indications for invasive Neuromonitoring, and family/guardian informed consent.
Who cannot join
- coagulation or platelet problems which cannot be corrected based on clinical indications
- anatomic abnormalities in skull or brain tissue precluding appropriate placement of an invasive brain monitor
- ongoing CNS or scalp infection,
- allergy to indocyanine green dye
- pregnancy
- lactation or pumping breast milk for the purpose of feeding an infant
Show all 9Show fewer
- increased bilirubin suggestive of cholestasis or biliary obstruction, (8) allergy to iodide
- severity of injury which leads the team or family to conclude that further advance medical care would be futile and limitation of the level of support is requested.
- Woman of childbearing potential will be excluded by urine or serum pregnancy test prior to conducting any study related procedures. . There is not a risk of pregnancy during this study as comatose patients will be monitored 24 hours a day in Intensive Care Units which have full visibility of patients.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennylvania Health System
Philadelphia, Pennsylvania, 19104
About this study
The goals of the project are to evaluate a noninvasive monitor of brain metabolism and blood flow in critically ill humans. If validated, such a reliable noninvasive brain blood flow and metabolism monitor, by allowing physiologic and pharmacologic decisions based on real-time brain physiology, potentially will become an important tool for clinicians in their efforts to prevent additional brain tissue death in patients admitted with stroke, brain hemorrhage and traumatic brain injury.
Read the detailed description
Many critically ill patients are admitted to the hospital with no infarcted brain tissue and yet, after a period of extremely intense and expensive critical care, the patients are discharged with new hospital-acquired dead brain tissue, with associated life-long disability or brain death. This situation arises from the critical barrier of there being no straightforward bedside methods to monitor cerebral blood flow (CBF) and its adequacy during progression of post-insult secondary brain damage. This is important because of the expectation that decrements in CBF in dangerous excess of decrements in cerebral metabolic rate for oxygen (CMRO2), if detected early, can be treated to avert brain infarction. Clinical examples of this issue, among many others, include post ischemic stroke edema, post thrombolysis hyperemia or occlusion, post SAH vasospasm, hyperemic and oligemic intracranial hypertension after traumatic brain injury or stroke, ICH associated global ischemia, and intra and post carotid endarterectomy oligemia and hyperperfusion.
Critical care physicians need a bedside monitor of CBF coupled to CMRO2. The CMRO2 data will allow delineation of adequacy of CBF as occasionally CBF decrements are simply matching changes in CMRO2. The lack of such monitoring capability has resulted in clinicians making often not helpful therapeutic decisions directed to non-neurologic endpoints, e.g., blood pressure, PaCO2 and so on, "hoping" that such interventions will have a desired effect on brain perfusion and metabolism.
Diffuse Correlation Spectroscopy (DCS) and Diffuse Optical Spectroscopy (DOS) are promising NNOM optical techniques under development at UPenn (Dr. Arjun Yodh) which can provide continuous bedside quantitative CBF, CMRO2 and oxygen extraction fraction (OEF) information. Determination of capability to detect anaerobic conditions, as the investigators propose doing, will make feasible the notion of individualized CBF, CMRO2, and OEF measurement and brain-directed therapeutic optimization by bedside caregivers. This will eventually support a significant change in the way Neurocritical Care is practiced, titrating therapy to neurophysiologic rather than cardiovascular/ pulmonary endpoints. UPenn research techniques presently provide information on relative quantitative changes in CBF and CMRO2 from baseline. The investigators propose also developing a method for measurement of absolute CBF and CMRO2 and further validating the absolute CBF against invasive thermodilution (ThD) CBF techniques. The investigators' long range goal and overall objective is to prevent in-hospital brain tissue death through development of improved bedside CBF/ CMRO2/OEF (NNOM) monitoring techniques.
- Conditions
- Traumatic Brain Injury, Ischemic Stroke, Intracerebral Hemorrhage, Subarachnoid Hemorrhage, Acute Anoxic Encephalopathy
- Being tested
- Indocyanine Green
- Medical subject headings
- Brain Injuries, Traumatic, Ischemic Stroke, Cerebral Hemorrhage, Subarachnoid Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Indocyanine GreenDrug
Also called Indocyanine Green Injection
ICG will be injected to derive absolute CBF and calibrate the DCS monitor to yield continuous absolute CBF. During each 12-hour monitoring session, for up to 14 days, the ICG will be injected at baseline(0.2 mg/kg,(4), every four hours (or less if signal is stable).
| Study group | Role | What they receive |
|---|---|---|
| Non-Invasive Monitoring | One non-invasive optode patch will be placed adjacent to the area of invasive monitoring and the second patch will be placed contralaterally. (12 hrs. daily is chosen primarily for budgetary reasons). The information for the non-invasive technology will be compared to the invasive technology.
ICG (Indocyanine Green) will be injected to derive absolute CBF and calibrate the DCS monitor to yield continuous absolute CBF. During each 12-hour monitoring session, for up to 14 days, the ICG will be injected at baseline(0.2 mg/kg,(4), every four hours (or less if signal is stable). Receives: Drug: Indocyanine Green |
What is being measured
The primary outcome is the main question the study is designed to answer.
The outcome variable will be the degree of correlation of ThD (thermodilution) CBF with optical CBF (cerebral blood flow).
Determine if the optical monitoring device's assessment of CBF is valid.
Measured: 12 days
Secondary outcomes (1)
The outcome variable will be whether the optical monitoring system detects an anaerobic condition based on specific criteria of low ThD CBF, low brain PO2(PbrO2), and high microdialysis lactate pyruvate ratio ( LPR).
Determine if the optical monitoring system can detect an anaerobic adverse condition in the brain which might lead to neural injury.
Measured: 12 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2016 (estimated)
- Study startDec 2015
- Primary completionOct 2018
- Study completion25 May 2022
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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- W. Andrew Kofke, MD, Principal investigator, University of Pennsylvania Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02983786
- Sponsor's protocol ID
- 819681
- Acronym
- NNOM
- Status last verified
- Sep 2022
- First submitted
- 3 Dec 2015
- Last updated
- 2 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: No, study data only remains with the study team. update reports will be submitted to the NIH, however individual patient data will not be included.
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Detection of Cerebral Ischemia With a Noninvasive Neurometabolic Optical Monitor
- ClinicalTrials.gov ID
- NCT02983786
- Acronym / sponsor ID
- NNOM / 819681
- Conditions
- Traumatic Brain Injury, Ischemic Stroke, Intracerebral Hemorrhage, Subarachnoid Hemorrhage, Acute Anoxic Encephalopathy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Dec 2015
- Primary completion
- Oct 2018 (actual)
- Study completion
- 25 May 2022 (actual)
- First posted
- 6 Dec 2016 (estimated)
- 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.
The goals of the project are to evaluate a noninvasive monitor of brain metabolism and blood flow in critically ill humans. If validated, such a reliable noninvasive brain blood flow and metabolism monitor, by allowing physiologic and pharmacologic decisions based on real-time brain physiology, potentially will become an important tool for clinicians in their efforts to prevent additional brain tissue death in patients admitted with stroke, brain hemorrhage and traumatic brain injury.
Detailed description
Many critically ill patients are admitted to the hospital with no infarcted brain tissue and yet, after a period of extremely intense and expensive critical care, the patients are discharged with new hospital-acquired dead brain tissue, with associated life-long disability or brain death. This situation arises from the critical barrier of there being no straightforward bedside methods to monitor cerebral blood flow (CBF) and its adequacy during progression of post-insult secondary brain damage. This is important because of the expectation that decrements in CBF in dangerous excess of decrements in cerebral metabolic rate for oxygen (CMRO2), if detected early, can be treated to avert brain infarction. Clinical examples of this issue, among many others, include post ischemic stroke edema, post thrombolysis hyperemia or occlusion, post SAH vasospasm, hyperemic and oligemic intracranial hypertension after traumatic brain injury or stroke, ICH associated global ischemia, and intra and post carotid endarterectomy oligemia and hyperperfusion.
Critical care physicians need a bedside monitor of CBF coupled to CMRO2. The CMRO2 data will allow delineation of adequacy of CBF as occasionally CBF decrements are simply matching changes in CMRO2. The lack of such monitoring capability has resulted in clinicians making often not helpful therapeutic decisions directed to non-neurologic endpoints, e.g., blood pressure, PaCO2 and so on, "hoping" that such interventions will have a desired effect on brain perfusion and metabolism.
Diffuse Correlation Spectroscopy (DCS) and Diffuse Optical Spectroscopy (DOS) are promising NNOM optical techniques under development at UPenn (Dr. Arjun Yodh) which can provide continuous bedside quantitative CBF, CMRO2 and oxygen extraction fraction (OEF) information. Determination of capability to detect anaerobic conditions, as the investigators propose doing, will make feasible the notion of individualized CBF, CMRO2, and OEF measurement and brain-directed therapeutic optimization by bedside caregivers. This will eventually support a significant change in the way Neurocritical Care is practiced, titrating therapy to neurophysiologic rather than cardiovascular/ pulmonary endpoints. UPenn research techniques presently provide information on relative quantitative changes in CBF and CMRO2 from baseline. The investigators propose also developing a method for measurement of absolute CBF and CMRO2 and further validating the absolute CBF against invasive thermodilution (ThD) CBF techniques. The investigators' long range goal and overall objective is to prevent in-hospital brain tissue death through development of improved bedside CBF/ CMRO2/OEF (NNOM) monitoring techniques.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Non-Invasive Monitoring | – | Drug: Indocyanine GreenOne non-invasive optode patch will be placed adjacent to the area of invasive monitoring and the second patch will be placed contralaterally. (12 hrs. daily is chosen primarily for budgetary reasons). The information for the non-invasive technology will be compared to the invasive technology. ICG (Indocyanine Green) will be injected to derive absolute CBF and calibrate the DCS monitor to yield continuous absolute CBF. During each 12-hour monitoring session, for up to 14 days, the ICG will be injected at baseline(0.2 mg/kg,(4), every four hours (or less if signal is stable). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Inclusion criteria will be age greater than or equal to 18 years, the diagnosis of SAH, TBI, ICH, and/or PIAE after cardiac arrest (post cardiac arrest coma) with GCS less than or equal to 8 (coma- clinical indications for invasive neuromonitoring), endotracheal intubation, clinical indications for invasive neuromonitoring, and family/guardian informed consent.
Key inclusion criteria (1 listed)
- Inclusion criteria will be age greater than or equal to 18 years, the diagnosis of SAH, TBI, ICH, and/or (PIAE) after cardiac arrest (post cardiac arrest coma) with GCS less than or equal to 8, endotracheal intubation, clinical indications for invasive Neuromonitoring, and family/guardian informed consent.
Key exclusion criteria (9 listed)
- coagulation or platelet problems which cannot be corrected based on clinical indications
- anatomic abnormalities in skull or brain tissue precluding appropriate placement of an invasive brain monitor
- ongoing CNS or scalp infection,
- allergy to indocyanine green dye
- 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 |
|---|---|---|
| Indocyanine GreenAlso: Indocyanine Green InjectionICG will be injected to derive absolute CBF and calibrate the DCS monitor to yield continuous absolute CBF. During each 12-hour monitoring session, for up to 14 days, the ICG will be injected at baseline(0.2 mg/kg,(4), every four hours (or less if signal is stable). | Drug | Non-Invasive Monitoring |
Primary outcome
The outcome variable will be the degree of correlation of ThD (thermodilution) CBF with optical CBF (cerebral blood flow).
Time frame: 12 days
Determine if the optical monitoring device's assessment of CBF is valid.
1 secondary outcome
The outcome variable will be whether the optical monitoring system detects an anaerobic condition based on specific criteria of low ThD CBF, low brain PO2(PbrO2), and high microdialysis lactate pyruvate ratio ( LPR).
Time frame: 12 Days
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 2 Sep 2022.
- Individual participant dataSharing planned: No. No, study data only remains with the study team. update reports will be submitted to the NIH, however individual patient data will not be included.
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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.
W. Andrew Kofke, MD principal investigator
University of Pennsylvania Health System
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 Traumatic Brain Injury and Ischemic Stroke, 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 1 inclusion and 9 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 2 Sep 2022. 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.
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?
The outcome variable will be the degree of correlation of ThD (thermodilution) CBF with optical CBF (cerebral blood flow). (time frame: 12 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 2 Sep 2022.