Ongoing Clinical Trials for Brain Injury
There are currently 7 ongoing clinical trials investigating new treatments for brain injury. These studies are exploring various medications including allopurinol, apomorphine, psilocybin, esketamine, ketamine, and sodium lactate in different types of brain injury, from newborns with congenital heart disease to adults with traumatic injuries, cardiac arrest, and disorders of consciousness. Trials are being conducted across multiple European countries including Belgium, Denmark, France, Italy, Netherlands, Romania, and Spain.
Clinical trial locations
- Belgium
- Study on Apomorphine Hydrochloride and Sodium Chloride for Patients with Severe Brain Injury and Disorders of Consciousness
- Study on Ketamine for Treating Patients with Severe Brain Injury and Disorders of Consciousness
- Study on the Effects of Sodium Lactate and Electrolyte Solution in Comatose Patients After Cardiac Arrest
- Denmark
- France
- Italy
- Netherlands
- Romania
- Spain
Study on Allopurinol Sodium for Brain Injury Prevention in Newborns with Critical Congenital Heart Disease Undergoing Heart Surgery
This trial is investigating whether allopurinol sodium can help protect the brain in newborns with critical congenital heart disease who need heart surgery. The study focuses on babies who require a specific type of surgery using a heart-lung machine called cardiopulmonary bypass within their first four weeks of life.
Who can participate: Newborn babies with serious heart conditions present at birth that require surgery within the first 4 weeks of life. The heart condition must be diagnosed either before or after birth. Both male and female newborns can join the study.
Who cannot participate: Newborns without critical congenital heart disease, those who do not need cardiac surgery with cardiopulmonary bypass, babies not at risk of brain injury related to their heart condition, or those outside the specified age range for the study.
What the trial involves: The main goal is to determine if giving allopurinol sodium shortly after birth and around the time of heart surgery can reduce brain injury. Babies receive either allopurinol sodium or a placebo through a vein. After surgery, MRI scans are used to check for brain injury, along with other tests to assess brain and heart function. The study also monitors the children’s development as they grow, including their movement and cognitive skills at different ages, up to 24 months.
Medication being tested: Allopurinol is being studied for its potential to protect the brain and heart. It works by inhibiting an enzyme called xanthine oxidase, which reduces the production of uric acid and oxidative stress, potentially protecting brain tissue.
Study on Apomorphine and Psilocybin for Recovery in Coma Patients with Acute Brain Injury
This trial explores whether apomorphine and psilocybin can help improve recovery in patients who are in a coma or have consciousness disorders due to sudden brain injuries. The study aims to determine if these treatments are safe for patients who are unresponsive and in intensive care.
Who can participate: Patients who are in a coma or have other consciousness disorders due to a sudden brain injury, are in the ICU and not responding to stimuli, have unconsciousness expected to last 3 days or more, and are 18 years old or older.
Who cannot participate: Patients who are not in a coma or do not have consciousness disorders, those without acute brain injury, patients not in the ICU, or those who are responsive.
What the trial involves: The study monitors how quickly patients wake up within 30 days and looks at other factors like eye response and brain activity. Participants receive either apomorphine (given as a subcutaneous infusion), psilocybin (taken as capsules), or a placebo. The trial aims to find the right dose that is safe for patients through a dose escalation study. Regular assessments evaluate overall health, brain function, and any potential side effects.
Medications being tested: Apomorphine works by stimulating dopamine receptors in the brain, which can help enhance neural activity. Psilocybin activates serotonin receptors in the brain, particularly the 5-HT2A receptor, which may influence mood and perception. Both are being tested to see if they can improve arousal and awareness in comatose patients.
Study on Apomorphine Hydrochloride and Sodium Chloride for Patients with Severe Brain Injury and Disorders of Consciousness
This international trial is examining whether apomorphine hydrochloride can improve consciousness levels in patients with severe brain injuries who have difficulty being aware of themselves or their surroundings.
Who can participate: Patients aged 18 to 70 years who are clinically stable, diagnosed with unresponsive wakefulness syndrome or minimally conscious state confirmed by at least two CRS-R tests in the last 14 days (with one in the last 7 days), and more than 4 weeks post-injury. Informed consent must be provided by the patient or their legal representative.
Who cannot participate: Patients outside the specified age range, without severe brain injury or disorder of consciousness, unable to provide informed consent or without a legal representative, those with medical conditions that could interfere with the study, currently participating in another trial, those with allergies to apomorphine, pregnant or breastfeeding women, and patients with substance abuse history or serious medical conditions affecting safety.
What the trial involves: The main focus is determining if apomorphine hydrochloride can improve consciousness levels. The medication is given as a subcutaneous infusion (under the skin) for up to 30 days. Researchers monitor changes in consciousness using the Coma Recovery Scale and other assessments including EEG (to measure brain activity), MRI and PET scans (to provide detailed brain pictures), and evaluations of sleep patterns and body temperature.
Medication being tested: Apomorphine hydrochloride, administered at a concentration of 5 mg/ml. It works by stimulating dopamine receptors in the brain, which can help enhance neural activity and potentially improve cognitive functions.
Study on Esketamine Hydrochloride and Sodium Chloride for Patients with Severe Acute Brain Injury
This trial investigates whether esketamine hydrochloride can reduce a specific type of harmful brain activity called cortical spreading depolarisations in patients with severe acute brain injuries from bleeding in or around the brain.
Who can participate: Patients 18 years or older admitted to the Neurointensive Care Unit with traumatic brain injury, aneurysmal subarachnoid hemorrhage (bleeding around the brain due to a burst blood vessel), or spontaneous intracerebral hemorrhage (sudden bleeding within brain tissue). They must be planned for supratentorial craniotomy or craniectomy surgery and expected to continue sedation and mechanical ventilation after surgery.
Who cannot participate: Patients with a history of subarachnoid hemorrhage, intracerebral hemorrhage, or traumatic brain injury.
What the trial involves: The study aims to assess how effective and safe esketamine is in reducing cortical spreading depolarisations, which are waves of electrical activity that can worsen brain injury. Participants receive either esketamine hydrochloride or sodium chloride through an infusion for up to 14 days. Researchers monitor how often these brain activities occur and check for side effects. Follow-up continues six months after treatment to assess recovery and overall health outcomes using the modified Rankin Scale and Glasgow Outcome Scale-Extended.
Medication being tested: S-ketamine (esketamine) works by blocking NMDA receptors in the brain, which are involved in the transmission of pain and the development of cortical spreading depolarizations. It is classified as a dissociative anesthetic.
Study on Ketamine for Treating Patients with Severe Brain Injury and Disorders of Consciousness
This trial evaluates whether ketamine can improve consciousness in patients who have experienced severe brain injury leading to disorders of consciousness, such as states where a person is awake but not aware of themselves or their surroundings.
Who can participate: Patients over 18 years old who are clinically stable, not dependent on medical ventilators, diagnosed with unresponsive wakefulness syndrome, minimally conscious state, or emerging from minimally conscious state (confirmed by at least two SECONDs assessments), more than 28 days post-injury, and with informed consent from a legal representative.
Who cannot participate: Patients with severe brain injury affecting consciousness, those outside the study age range, patients who do not match the specific group being studied, or those unable to give consent or considered vulnerable populations.
What the trial involves: The study compares ketamine effects to placebo in improving consciousness. Ketamine is given through intravenous infusion. Researchers monitor any new signs of consciousness, such as the ability to respond to commands, and assess changes in brain activity using fMRI (which looks at brain activity by detecting blood flow changes) and EEG (which records electrical brain activity). The study measures brain complexity and connectivity, evaluates spasticity, range of motion, and alpha connectivity in the brain.
Medication being tested: Ketamine (Ketalar 10mg/ml) works by blocking NMDA receptors in the brain, which are involved in pain transmission and mood regulation. It is classified as a dissociative anesthetic.
Study on the Effects of Sodium Lactate and Electrolyte Solution in Comatose Patients After Cardiac Arrest
This trial examines whether hypertonic sodium lactate can help reduce brain injury in patients who are in a coma after experiencing cardiac arrest, when the heart suddenly stops beating.
Who can participate: Patients older than 18 years who have had sustained return of spontaneous circulation for at least 20 minutes (meaning the heart started beating again on its own), are in a comatose state with a Glasgow Coma Scale score below 9 (indicating unconsciousness and lack of response to surroundings), and where the time to return of spontaneous circulation was more than 15 minutes.
Who cannot participate: Patients with brain injury unrelated to lack of oxygen, those not in a coma, patients who have not experienced cardiac arrest, those without post-cardiac arrest syndrome, patients outside the specified age range, or those not part of the vulnerable population being studied.
What the trial involves: The treatment uses sodium lactate solution (SODIO LATTATO MONICO) and Plasmalyte A Viaflo (containing electrolytes like magnesium chloride, potassium chloride, sodium chloride, sodium acetate, and sodium gluconate) given through intravenous infusion. The study looks at protein levels in the blood that indicate brain injury, patient recovery in terms of brain function, and overall health status during hospitalization. Assessments include neuron-specific enolase levels at 48 hours, cerebral performance category score at 90 days, length of stay in intensive care and hospital, mortality rates, and seizure episodes.
Medication being tested: Hypertonic sodium lactate works by providing an energy substrate to the brain, potentially improving cellular metabolism and reducing injury. It is used for its potential neuroprotective effects.
Study on Psilocybin and Apomorphine for Improving Consciousness in Patients with Coma and Brain Injury
This trial explores whether psilocybin and apomorphine can help improve consciousness levels in patients who are in a coma or have other consciousness disorders due to brain injuries.
Who can participate: Patients who are in a state where they do not respond to stimuli due to brain injury (traumatic or non-traumatic) or due to a medical or surgical condition leading to coma not caused by medication, where doctors expect unconsciousness to last at least 3 days, and who are 18 years old or older.
Who cannot participate: Patients not in a coma or without consciousness disorders, those who have not experienced brain injury, patients outside the specified age range, those not belonging to the specified trial group, or not part of the vulnerable population selected for the study.
What the trial involves: The study observes changes in consciousness levels within 3 to 6 hours after treatment using a composite score including the FOUR score and SECONDs. Some patients receive psilocybin (25 mg capsules taken orally), some receive apomorphine (given as subcutaneous infusion), and others may receive a placebo. Additional evaluations include pupillary function assessed through pupillometry, neurovascular coupling measured using NIRS-EEG on days 1 and 7, overall health outcome after 90 days using the GOS-E scale, and the number of days alive outside the ICU.
Medications being tested: Psilocybin activates serotonin receptors in the brain, which may help stimulate awareness and arousal. Apomorphine stimulates dopamine receptors, affecting motor control and alertness, which might help improve the patient’s level of awareness and responsiveness.
Summary
The seven ongoing clinical trials for brain injury represent a diverse range of research efforts across multiple European countries. Denmark is notably active with three trials, while Belgium hosts three different studies. The Netherlands, Romania, France, Spain, and Italy each participate in one or more trials.
A significant focus of current research centers on disorders of consciousness following severe brain injury, with several trials investigating apomorphine and psilocybin for their potential to improve awareness and responsiveness in comatose patients. Apomorphine appears in four different trials, making it the most frequently studied medication across this set of research. Ketamine and its derivative esketamine are being explored in two trials for their neuroprotective properties.
The trials address brain injury across different patient populations, from newborns with congenital heart disease requiring protective interventions during surgery, to adults with traumatic brain injuries, hemorrhagic strokes, and cardiac arrest-related brain damage. This breadth reflects the complex nature of brain injury and the need for targeted approaches based on the underlying cause and patient age.
Several trials are investigating medications traditionally used for other conditions, such as apomorphine (typically used for Parkinson’s disease) and psilocybin (a psychedelic compound), demonstrating innovative approaches to finding treatments for consciousness disorders. The research also includes newer agents like esketamine and established treatments like allopurinol being tested in novel applications.
