Carbon Dioxide for Stroke in Children
(COMIC Trial)
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Washington University School of Medicine
Must not be taking: Vasodilators
Disqualifiers: Pregnancy, Epilepsy, Stroke, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The purpose of this research study is to better understand how blood flow and metabolism change can influence brain development in the early decades of life.
We will examine brain blood flow and metabolism using magnetic resonance imaging (MRI). The brain's blood vessels expand and constrict to regulate blood flow based on the brain's needs. The amount of expanding and contracting the blood vessels can do varies by age. The brain's blood flow changes in small ways during everyday activities, such as normal brain growth, exercise, or deep concentration. Significant illness or psychological stress may increase the brain's metabolic demand or cause other bigger changes in blood flow. If blood vessels are not able to expand to give more blood flow when metabolic demand is high, the brain may not get all of the oxygen it needs. In extreme circumstances, if the brain is unable to get enough oxygen for a long time, a stroke may occur. Sometimes small strokes occur without other noticeable changes and are only detectable on an MRI. These are sometimes called "silent strokes." In less extreme circumstances, not having as much oxygen as it wants may cause the brain to grow and develop more slowly than it should.
One way to test the ability of blood vessels to expand is by measuring blood flow while breathing in carbon dioxide. Carbon dioxide causes blood vessels in the brain to dilate without increasing brain metabolism.
During this study participants may be asked to undergo a blood draw, MRI, and potential neuropsychological assessments. It is also possible that the study team will use a special mask to control the amount of carbon dioxide the participants breathe in so they don't breathe in too much.
Will I have to stop taking my current medications?
If you are taking vasodilatory medications like sildenafil or verapamil, you will need to stop taking them to participate in this trial. The protocol does not specify other medication restrictions.
What data supports the effectiveness of the treatment Carbon Dioxide for stroke in children?
Some studies suggest that carbon dioxide can improve blood flow to the brain, which might help in conditions like stroke. For example, research has shown that higher levels of carbon dioxide during anesthesia can lead to better recovery outcomes, indicating its potential to enhance brain function.
12345Is carbon dioxide safe for use in medical procedures?
In a study with dogs, large amounts of carbon dioxide were injected into arteries, and no harmful effects were observed, suggesting it may be safe for use in certain medical procedures.
678910How does the carbon dioxide treatment for stroke in children differ from other treatments?
The carbon dioxide treatment for stroke in children is unique because it involves inhaling carbon dioxide to increase cerebral blood flow, which is different from other treatments that may not focus on altering blood flow through gas inhalation. This approach leverages the vasodilatory effect of carbon dioxide to potentially improve brain oxygenation, which is not a standard method for treating strokes in children.
1112131415Eligibility Criteria
This trial is for healthy individuals or those with sickle cell anemia, aged 3-50, who can have an MRI without sedation. It's not for pregnant women, people on certain blood flow medications, those with severe psychiatric conditions as determined by the study leader, a history of stroke or epilepsy.Inclusion Criteria
I have sickle cell disease (Hb SS) or Sβ-thalassemia.
I sometimes have headaches but don't take daily medication for them.
I am not taking any medication that widens my blood vessels.
+5 more
Exclusion Criteria
I have never had epilepsy.
No significant psychiatric history, defined as having a severe psychiatric diagnosis, per PI discretion
I have never had a stroke or brain blood vessel issues.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Baseline Assessment
Participants undergo initial MRI scans and baseline neuropsychological assessments
1-2 weeks
1 visit (in-person)
Intervention
Participants may undergo MRI scans while breathing controlled amounts of carbon dioxide to assess cerebral blood flow and oxygen metabolism
4-6 weeks
2-3 visits (in-person)
Follow-up
Participants are monitored for changes in brain blood flow and metabolism over time
4 weeks
Participant Groups
The study tests how well brain blood vessels can handle increased demand by using carbon dioxide to dilate them during MRI scans. This helps understand oxygen metabolism and its impact on brain development and potential silent strokes in children.
3Treatment groups
Active Control
Group I: Healthy ControlsActive Control1 Intervention
Group II: Extracorporeal Membrane Oxygenation survivorsActive Control1 Intervention
Group III: Sickle Cell Anemia participantsActive Control1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Washington University of St. LouisSaint Louis, MO
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Who Is Running the Clinical Trial?
Washington University School of MedicineLead Sponsor
References
Multimodal assessment using early brain CT and blood pH improve prediction of neurologic outcomes after pediatric cardiac arrest. [2020]Early prediction of neurologic prognosis in children resuscitated from cardiac arrest is a major challenge. This study aimed to investigate the usefulness of a combined model based on brain computed tomography (CT) and initial blood gas analysis to predict neurologic prognoses in pediatric patients after cardiac arrest.
Carbon dioxide homeostasis and recovery after general anaesthesia. [2019]The influence of different levels of carbon dioxide during general anaesthesia on postoperative recovery was studied. Sixty female patients were divided into two age groups. Thirty patients were over 60 years old and 30 patients were under 46 years old. Artificial ventilation with added carbon dioxide during general anaesthesia with thiopentone, nitrous oxide-oxygen, alcuronium and fentanyl was used. According to the arterial CO2 tension, patients were allocated to subgroups: hypercarbic, PaCO2 7.3 kPa, normocarbic, PaCO2 5.3 kPa and two different levels of hypocarbia: older patients PaCO2 3.7 kPa and younger patients PaCO2 2.9 kPa. As criteria for recovery, a battery of recovery tests and postoperative questionnaires were used. Regardless of age, patients subjected to hypercarbic ventilation scored better in the recovery tests than patients subjected to normo- or hypocarbia. Normocarbic ventilation also gave better results than hypocarbic ventilation. The level of hypocarbia used in the older patients and that used in the younger patients, though different, resulted in nearly the same deterioration of scoring in the recovery tests. This deterioration was seen in some patients up to 48 h postoperatively. No subjective differences were elicited from the questionnaires after various types of ventilation.
Brain tissue oxygen monitoring identifies cortical hypoxia and thalamic hyperoxia after experimental cardiac arrest in rats. [2021]Optimization of cerebral oxygenation after pediatric cardiac arrest (CA) may reduce neurological damage associated with the post-CA syndrome. We hypothesized that important alterations in regional partial pressure of brain tissue oxygen (PbO2) occur after resuscitation from CA and that clinically relevant interventions such as hyperoxia and blood pressure augmentation would influence PbO2.
CO2 combining power and outcomes in patients with acute ischaemic stroke or transient ischaemic attack. [2022]Label="BACKGROUND AND PURPOSE">The clinical significance of carbon dioxide combining power (CO2CP) in ischaemic cerebrovascular disease is not well established, and the role of CO2CP in the prognosis of acute ischaemic stroke (AIS) or transient ischaemic attack (TIA) has not been reported. The objective of the study was to investigate the associations between CO2CP and clinical outcomes in patients with AIS or TIA.
There is no evidence that carbon dioxide-enriched oxygen before apnea affects the time to arterial desaturation, but it might improve cerebral oxygenation in anesthetized obese patients: a single-blinded randomized crossover trial. [2023]Label="PURPOSE">Carbon dioxide (CO2) increases cerebral perfusion. The effect of CO2 on apnea tolerance, such as after anesthesia induction, is unknown. This study aimed to assess if cerebral apnea tolerance can be improved in obese patients under general anesthesia when comparing O2/Air (95%O2) to O2/CO2 (95%O2/5%CO2).
Acute effects of acetazolamide on cerebral blood flow in man. [2013]We have followed the time course of the effect of the carbonic anhydrase inhibitor acetazolamide injected i.v. in unanesthetized healthy human beings. The dose administered was 500 mg as a bolus. Cerebral blood flow (CBF) was measured continuously before, during and after the injection, using a pulsed ultrasound doppler system, which measured the instantaneous mean velocity across the lumen of the internal carotid artery, just below its entrance into the skull. Ventilation, heart-rate, end-expiratory PCO2, arterial PCO2, pH and systemic blood pressure was also measured. We found that acetazolamide caused a rise in CBF which could be detected as early as 2 min after the injection. A maximal average response of 75% increase in CBF was seen after 25 min. The half-time of the declining phase of the response was 95 min. There were no systematic differences in the CO2 reactivities, given as delta CBF/delta PACO2 in % of CBF at normocapnia, before and after acetazolamide injection, regardless of the absolute PACO2 level. The present dose of the drug caused no change in ventilation, alveolar and arterial PCO2 or in arterial blood pH indicating that the carbonic anhydrase was not fully inhibited. Our observations show that acetazolamide nevertheless caused a rapid vasodilation in the brain and over a wide range of PCO2's. We suggest that this agent has a local vasodilator effect on the cerebral arterioles, unrelated to its specific effects as a carbonic anhydrase inhibitor.
Acetazolamide improves cerebral hemodynamics in CADASIL. [2016]Acetazolamide (ACZ), a carbonic anhydrase inhibitor, causes a rapid increase in cerebral blood flow (CBF) in patients with cerebrovascular diseases. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease caused by mutations in the NOTCH3 gene. Recent studies suggest that ACZ infusion significantly increases cerebral perfusion, even within areas of impaired cerebral vasoreactivity in CADASIL patients. This study evaluates the efficacy and tolerance of a 24-week treatment with 250 mg/d ACZ, which could be chronically implemented to improve cerebral hemodynamics in CADASIL.
Role of Carbonic Anhydrase in Cerebral Ischemia and Carbonic Anhydrase Inhibitors as Putative Protective Agents. [2021]Ischemic stroke is a leading cause of death and disability worldwide. The only pharmacological treatment available to date for cerebral ischemia is tissue plasminogen activator (t-PA) and the search for successful therapeutic strategies still remains a major challenge. The loss of cerebral blood flow leads to reduced oxygen and glucose supply and a subsequent switch to the glycolytic pathway, which leads to tissue acidification. Carbonic anhydrase (CA, EC 4.2.1.1) is the enzyme responsible for converting carbon dioxide into a protons and bicarbonate, thus contributing to pH regulation and metabolism, with many CA isoforms present in the brain. Recently, numerous studies have shed light on several classes of carbonic anhydrase inhibitor (CAI) as possible new pharmacological agents for the management of brain ischemia. In the present review we summarized pharmacological, preclinical and clinical findings regarding the role of CAIs in strokes and we discuss their potential protective mechanisms.
Cerebral angiography with gaseous carbon dioxide CO2. [2016]Large quantities of gaseous carbon dioxide CO2 were rapidly injected into the ascending aorta or common carotid artery of 14 dogs. Good filling of the arteries and intracranial veins was documented by cineangiography or digital subtraction angiography. No adverse effects occurred as a result of this procedure: the electroencephalogram showed no changes throughout the experiments and the dogs were neurologically normal for up to 6 months of follow-up. Further investigation of carbon dioxide as an arterial and cerebrovascular contrast agent is justified based on these results.
Dissociation of vasoreactivity to acetazolamide and hypercapnia. Comparative study in patients with chronic occlusive major cerebral artery disease. [2019]The aim of this study was to compare the effect of vasodilative stimuli for the measurement of cerebrovascular reactivity obtained by acetazolamide and hypercapnia in patients with chronic occlusive major cerebral artery disease.
Age-related carbon dioxide reactivity in children after moderate and severe traumatic brain injury. [2017]OBJECTIVE The objective of this study is to assess carbon dioxide reactivity (CO2R) in children following traumatic brain injury (TBI). METHODS This prospective observational study enrolled children younger than 18 years old following moderate and severe TBI. Thirty-eight mechanically ventilated children had daily CO2R testing performed by measuring changes in their bilateral middle cerebral artery flow velocities using transcranial Doppler ultrasonography (TCD) after a transient increase in minute ventilation. The cohort was divided into 3 age groups: younger than 2 years (n = 12); 2 to 5 years old (n = 9); and older than 5 years (n = 17). RESULTS Children younger than 2 years old had a lower mean CO2R over time. The 2-5-year-old age group had higher mean CO2R than younger patients (p = 0.01), and the highest CO2R values compared with either of the other age groups (vs > 5 years old, p = 0.046; vs
Do acute stroke patients develop hypocapnia? A systematic review and meta-analysis. [2020]Label="PURPOSE" NlmCategory="OBJECTIVE">Carbon dioxide (CO2) is a potent cerebral vasomotor agent. Despite reduction in CO2 levels (hypocapnia) being described in several acute diseases, there is no clear data on baseline CO2 values in acute stroke. The aim of the study was to systematically assess CO2 levels in acute stroke.
Transcranial Doppler: response of cerebral blood-flow velocity to carbon dioxide in anaesthetized children. [2018]To determine the effect of carbon dioxide on the cerebral circulation in anaesthetized infants and children, 13 healthy children, ASA physical status I or II, between three months and seven years of age and scheduled for urologic surgery, were studied. Anaesthesia was induced with thiopentone and vecuronium. After tracheal intubation, anaesthesia was maintained with 70 per cent nitrous oxide in oxygen, fentanyl 2 micrograms.kg-1, vecuronium 0.05 mg.kg-1 and 0.8-1.0 per cent end-tidal isoflurane. A caudal block was performed before surgery. Systolic arterial pressure, heart rate, oxygen saturation, temperature, and end-tidal isoflurane were maintained constant. Ventilation was adjusted to achieve an end-tidal PCO2 (PETCO2) of 20 mmHg. The PETCO2 was then randomly adjusted between 20 and 80 mmHg by the addition of carbon dioxide from an exogenous source. Cerebral blood flow velocity increased logarithmically and directly with the PETCO2 (r2 = 0.56). There were no complications associated with the use of transcranial Doppler sonography. These data indicate that CO2 has a direct effect on the velocity of blood in the middle cerebral artery in infants and children anaesthetized with isoflurane.
High blood carbon dioxide variability and adverse outcomes in neonatal hypoxic ischemic encephalopathy. [2015]Hypocarbia during the first 12 h of life is associated with mortality and disability in neonatal hypoxic ischemic encephalopathy (HIE). Notable variation in arterial carbon dioxide tension (PaCO2) during the first 4 d of life is related to severe intraventricular hemorrhages in preterm infants. We examined the association between PaCO2 during 72 h of whole-body therapeutic hypothermia for neonatal HIE and 2-year neurodevelopmental outcomes.
Improvement of brain tissue oxygenation by inhalation of carbogen. [2016]Hyperoxic therapy for cerebral ischemia is suspected to reduce cerebral blood flow (CBF), due to the vasoconstrictive effect of oxygen on cerebral arterioles. We hypothesized that vasodilation predominates when 5% CO(2) is added to the inhaled oxygen (carbogen). Therefore, we used positron emission tomography (PET) to measure CBF and cerebral metabolic rate of oxygen (CMRO(2)) during inhalation of test gases (O(2), CO(2), carbogen and atmospheric air) in 10 healthy volunteers. Arterial blood gases were recorded during administration of each gas. The data were analyzed with volume-of-interest and voxel-based statistical methods. Inhalation of CO(2) or carbogen significantly increased global CBF, whereas pure oxygen decreased global CBF. The CMRO(2) generally remained unchanged, except in white matter during oxygen inhalation relative to condition of atmospheric air inhalation. The volume-of-interest results were confirmed by statistical cluster analysis. Oxygen and carbogen were equally potent in increasing oxygen saturation of arterial blood (Sa(O2)). The present data demonstrate that inhalation of carbogen increases both CBF and Sa(O2) in healthy adults. In conclusion we speculate that carbogen inhalation is sufficient for optimal oxygenation of healthy brain tissue, whereas carbogen induces concomitant increases of CBF and Sa(O2).