TBINCT02990078
Non-invasive Measurement of Cerebrovascular Reactivity After Traumatic Brain Injury
An observational study of TBI, run by University of Pennsylvania at 1 site in United States.
Trial summary
The investigators will longitudinally measure cerebrovascular reactivity (CVR) by functional near-infrared spectroscopy (fNIRS) in acute (≤3 days from injury), subacute, and chronic phases after TBI as a biomarker of TCVI as compared to healthy controls. CVR will be measured by fNIRS response to hypercapnia. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- TBI
- What is being tested?
- Sildenafil citrate, Functional Near Infared Spectroscopy and Hypercapnia Challenge
- Type of treatment
- Pill or oral medicine, Medical device
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2016to 30 Sep 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Male and female, aged 18 or older, presenting with a diagnosis of traumatic brain injury (TBI) and healthy peer control volunteers .
Who may be able to join
- Men and women, aged ≥18
- CT evidence of TBI-linked abnormality
- Traumatic subarachnoid hemorrhage
- Intracerebral hemorrhage/contusion
- Subdural/epidural hematoma
- Ability to undergo fNIRS testing with hypercapnia challenge
- Subject able to provide informed consent
- Attending of record agrees to include subject in study
Who cannot join
- Unstable respiratory or hemodynamic status
- Evidence of penetrating brain injury
- TBI requiring craniotomy or craniectomy
- Evidence or risk of ICP crisis
- History of disabling pre-existing neurologic disorder (e.g. dementia, uncontrolled epilepsy, multiple sclerosis, strokes, brain tumors, prior severe TBI, or other disorder that confounds interpretation of NIRS testing or neuropsychological results)
- History of pre-existing disabling mental illness (e.g. major depression or schizophrenia)
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- Exclusion criteria for sildenafil administration:
- History of melanoma
- current use of organic nitrate vasodilators
- current use of ritonavir (HIV-protease inhibitor)
- current use of erythromycin, ketoconazole, or itraconazole; current use of cimetidine
- current use of alpha-blockers such as doxazosin (Cardura), tamsulosin (Flomax), and terazosin (Hytrin) prazosin (Minipres)
- resting hypotension (systolic BP <90)
- severe renal insufficiency
- hepatic cirrhosis
- acute ischemic stroke within past 2 months
- acute myocardial infarction within past 2 months
- unstable angina pectoris
- acute or chronic heart failure
- retinitis pigmentosa
- pregnant or breastfeeding female
- known hypersensitivity or allergy to sildenafil
- Unstable cardiac status that constitutes a contraindication to sexual activity
- Inability to read and communicate in English (necessary to obtain reliable neuropsychometric data)
- Nursing mothers
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, 19104
About this study
Official title: Cerebrovascular Reactivity Assessed With Functional Near-infrared Spectroscopy as a Biomarker of Traumatic Microvascular Injury After Moderate-severe Traumatic Brain Injury
The investigators will longitudinally measure cerebrovascular reactivity (CVR) by functional near-infrared spectroscopy (fNIRS) in acute (≤3 days from injury), subacute, and chronic phases after TBI as a biomarker of TCVI as compared to healthy controls. CVR will be measured by fNIRS response to hypercapnia. The investigators hypothesize that CVR will be decreased after TBI and that these decreases will correlate with clinical outcomes. Furthermore, the investigators predict that administration of a vasodilatory medication (sildenafil) will augment CVR after TBI.
- Conditions
- TBI
- Being tested
- Sildenafil citrate, Functional Near Infared Spectroscopy, Hypercapnia Challenge
- Keywords
- TBI, CVR, Hypercapnia, fNIRS
- Medical subject headings
- Hypercapnia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil citrateDrug
Also called Viagra
Sildenafil is a potent and specific PDE5 inhibitor, which was initially developed for the treatment of hypertension and angina. Its effectiveness as a treatment for male erectile dysfunction became apparent during Phase I clinical trials, and the focus of drug development shifted to this indication. In patients with cerebrovascular dysfunction, a few preliminary studies have used sildenafil to increase CVR. Participants in the pilot study had CVR tested in response to hypercapnia measured twice, at baseline and then 1 hour after administration of sildenafil citrate, 50 mg by mouth. The investigators have an IND exemption for the uses in this study.
Functional Near Infared SpectroscopyDevice
Also called fNIRS
Functional near-infrared spectroscopy (fNIRS) will be used to measure regional cerebral blood flow and cerebrovascular reactivity. are connected to the scalp and surrounding detectors a few cm away detect the light as it scatters through the underlying tissues. The technique is able to detect changes in the absorption spectrum of the tissue corresponding to the concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR), and indicate local perfusion changes.
Hypercapnia ChallengeOther
The study device is a Douglas Bag that traditionally is designed to measure respiratory exchange. It consists of large bag attached to a mouthpiece utilized to hold either expired air from the subject or filled with different concentrations of air to be aspired. For the purposes of this study, the Douglas Bag will be utilized to induce hypercapnia in the subject. The bag is equipped with a switch that allows rapid shifting from room air to 5% CO2 each minute over 7 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Acute TBI | Subjects will be recruited from the neurointensive care unit within 72 hours of their injury. At the time of informed consent, the investigators will perform fNIRS testing with a hypercapnia challenge, fNIRS with hypercapnia challenge 60 minutes after a single oral dose of 50mg sildenafil citrate, outcome qustionaires and symptom checklists (including: Glasgow Outcomes Scale-Extended, Rivermead Post-Concussive Symptom Questionnaire, Brief Symptom Inventory, Alcohol Consumption Questionnaire, Patient Health Questionnaire, and Insomnia Severity Index). This will all be administered again at 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, and 4 years after injury. Receives: Drug: Sildenafil citrate; Device: Functional Near Infared Spectroscopy; Other: Hypercapnia Challenge | |
| Sub-acute/Chronic TBI | Subjects who suffered a TBI previously and have now entered a subacute or chronic phase of their TBI will be approached by the research team at their clinic visit with a TBI specialist. In those subjects, study timing will be based on the time of their original injury, therefore will start study visits at the next possible time point. Receives: Drug: Sildenafil citrate; Device: Functional Near Infared Spectroscopy; Other: Hypercapnia Challenge | |
| Healthy Controls | The investigators will also enroll healthy "peer controls". These control subjects will be family members and friends of TBI subjects. These peer controls are likely to have similar environmental and socioeconomic exposures/support which may impact recovery after TBI and may also impact CVR. These control subjects will meet the same inclusion/exclusion criteria as TBI subjects without the requirement for an injury or acute brain imaging. These subjects will be tested in the same way as both TBI groups, but will only have one visit. Receives: Drug: Sildenafil citrate; Device: Functional Near Infared Spectroscopy; Other: Hypercapnia Challenge |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in CVR prior to sildenafil administration
Measured: < 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years
Secondary outcomes (2)
Change CVR after sildenafil administration
Measured: <72 hours, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years
Relationship of CVR with symptom reports, as measured by the Neurobehavioral Symptom Inventory (NBSI).
Measured: < 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2016 (estimated)
- Study startDec 2016
- Primary completion30 Jun 2022
- Study completion30 Sep 2022
Why it stopped: Sufficient sample size enrolled to demonstrate scientific goals of the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TBIStudies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ramon Diaz-Arrastia, University of Pennsylvania
- Investigators
- Ramon Diaz-Arrastia, MD, PhD, Principal investigator, University of Pennsylvania Perelman School of Medicine, Department of Neurology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02990078
- Sponsor's protocol ID
- 825942
- Status last verified
- Oct 2022
- First submitted
- 5 Dec 2016
- Last updated
- 13 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cerebrovascular Reactivity Assessed With Functional Near-infrared Spectroscopy as a Biomarker of Traumatic Microvascular Injury After Moderate-severe Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT02990078
- Acronym / sponsor ID
- 825942
- Conditions
- TBI
- Keywords
- TBI, CVR, Hypercapnia, fNIRS
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Sufficient sample size enrolled to demonstrate scientific goals of the study
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Dec 2016 (actual)
- Primary completion
- 30 Jun 2022 (actual)
- Study completion
- 30 Sep 2022 (actual)
- First posted
- 12 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 investigators will longitudinally measure cerebrovascular reactivity (CVR) by functional near-infrared spectroscopy (fNIRS) in acute (≤3 days from injury), subacute, and chronic phases after TBI as a biomarker of TCVI as compared to healthy controls. CVR will be measured by fNIRS response to hypercapnia. The investigators hypothesize that CVR will be decreased after TBI and that these decreases will correlate with clinical outcomes. Furthermore, the investigators predict that administration of a vasodilatory medication (sildenafil) will augment CVR after TBI.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Acute TBI | – | Drug: Sildenafil citrate, Device: Functional Near Infared Spectroscopy, Other: Hypercapnia ChallengeSubjects will be recruited from the neurointensive care unit within 72 hours of their injury. At the time of informed consent, the investigators will perform fNIRS testing with a hypercapnia challenge, fNIRS with hypercapnia challenge 60 minutes after a single oral dose of 50mg sildenafil citrate, outcome qustionaires and symptom checklists (including: Glasgow Outcomes Scale-Extended, Rivermead Post-Concussive Symptom Questionnaire, Brief Symptom Inventory, Alcohol Consumption Questionnaire, Patient Health Questionnaire, and Insomnia Severity Index). This will all be administered again at 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, and 4 years after injury. |
| Sub-acute/Chronic TBI | – | Drug: Sildenafil citrate, Device: Functional Near Infared Spectroscopy, Other: Hypercapnia ChallengeSubjects who suffered a TBI previously and have now entered a subacute or chronic phase of their TBI will be approached by the research team at their clinic visit with a TBI specialist. In those subjects, study timing will be based on the time of their original injury, therefore will start study visits at the next possible time point. |
| Healthy Controls | – | Drug: Sildenafil citrate, Device: Functional Near Infared Spectroscopy, Other: Hypercapnia ChallengeThe investigators will also enroll healthy "peer controls". These control subjects will be family members and friends of TBI subjects. These peer controls are likely to have similar environmental and socioeconomic exposures/support which may impact recovery after TBI and may also impact CVR. These control subjects will meet the same inclusion/exclusion criteria as TBI subjects without the requirement for an injury or acute brain imaging. These subjects will be tested in the same way as both TBI groups, but will only have one visit. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Male and female, aged 18 or older, presenting with a diagnosis of traumatic brain injury (TBI) and healthy peer control volunteers .
Key inclusion criteria (8 listed)
- Men and women, aged ≥18
- CT evidence of TBI-linked abnormality
- Ability to undergo fNIRS testing with hypercapnia challenge
- Subject able to provide informed consent
- Attending of record agrees to include subject in study
Key exclusion criteria (25 listed)
- Unstable respiratory or hemodynamic status
- Evidence of penetrating brain injury
- TBI requiring craniotomy or craniectomy
- Evidence or risk of ICP crisis
- History of disabling pre-existing neurologic disorder (e.g. dementia, uncontrolled epilepsy, multiple sclerosis, strokes, brain tumors, prior severe TBI, or other disorder that confounds interpretation of NIRS testing or neuropsychological results)
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 |
|---|---|---|
| Sildenafil citrateAlso: ViagraSildenafil is a potent and specific PDE5 inhibitor, which was initially developed for the treatment of hypertension and angina. Its effectiveness as a treatment for male erectile dysfunction became apparent during Phase I clinical trials, and the focus of drug development shifted to this indication. In patients with cerebrovascular dysfunction, a few preliminary studies have used sildenafil to increase CVR. Participants in the pilot study had CVR tested in response to hypercapnia measured twice, at baseline and then 1 hour after administration of sildenafil citrate, 50 mg by mouth. The investigators have an IND exemption for the uses in this study. | Drug | Acute TBI, Healthy Controls, Sub-acute/Chronic TBI |
| Functional Near Infared SpectroscopyAlso: fNIRSFunctional near-infrared spectroscopy (fNIRS) will be used to measure regional cerebral blood flow and cerebrovascular reactivity. are connected to the scalp and surrounding detectors a few cm away detect the light as it scatters through the underlying tissues. The technique is able to detect changes in the absorption spectrum of the tissue corresponding to the concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR), and indicate local perfusion changes. | Device | Acute TBI, Healthy Controls, Sub-acute/Chronic TBI |
| Hypercapnia ChallengeThe study device is a Douglas Bag that traditionally is designed to measure respiratory exchange. It consists of large bag attached to a mouthpiece utilized to hold either expired air from the subject or filled with different concentrations of air to be aspired. For the purposes of this study, the Douglas Bag will be utilized to induce hypercapnia in the subject. The bag is equipped with a switch that allows rapid shifting from room air to 5% CO2 each minute over 7 minutes. | Other | Acute TBI, Healthy Controls, Sub-acute/Chronic TBI |
Primary outcome
Change in CVR prior to sildenafil administration
Time frame: < 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years
2 secondary outcomes
Change CVR after sildenafil administration
Time frame: <72 hours, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years
Relationship of CVR with symptom reports, as measured by the Neurobehavioral Symptom Inventory (NBSI).
Time frame: < 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years
Results and safety
The study was stopped early (reason given: Sufficient sample size enrolled to demonstrate scientific goals of the study). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2022.
- 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.
Ramon Diaz-Arrastia, MD, PhD principal investigator
University of Pennsylvania Perelman School of Medicine, Department of Neurology
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 TBI, 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 8 inclusion and 25 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: stopped early, as of the sponsor's last update on 13 Oct 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 was stopped early (reason given: Sufficient sample size enrolled to demonstrate scientific goals of the study). Results are not available in the source record.
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?
Change in CVR prior to sildenafil administration (time frame: < 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years). 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 13 Oct 2022.