Clinical Trials for Epilepsy: Challenges and Promises of Wearable Devices
By: Vera Kovacevic, PhD
Interviewee: R. Edward Hogan, Professor of Neurology and Director of the Adult Epilepsy Center at Washington University in St. Louis
Clinical Trials for Epilepsy: Challenges and Promises of Wearable Devices
By: Vera Kovacevic, PhD
Interviewee: R. Edward Hogan, Professor of Neurology and Director of the Adult Epilepsy Center at Washington University in St. Louis
Patients with epileptic seizures may not remember most of their seizures, so finding a reliable method to detect and track seizures would be beneficial for epilepsy clinical trials.
Epilepsy is one of the most common neurological diseases in the world, with around 50 million people worldwide having received this diagnosis. In the US alone, over 3.4 million people have epilepsy, which is a little over one percent of the US population.
Wearable devices for epilepsy are becoming gradually more popular to detect and manage seizures. These devices are designed to help people with epilepsy and their caregivers track seizure activity, provide alerts and help manage medication schedules.
In clinical epilepsy, it can be difficult to evaluate the disease based on patient or caregiver reports and temporary clinical tests. As a result, wearable devices have started to be used in clinical trials for epilepsy to supplement data from self-reported seizure diaries and caregiver reports.
For example, several clinical studies have used Empatica’s Embrace watch to monitor seizure activity and medication adherence. It is also the world’s only wrist-worn wearable for epilepsy that is cleared by the US Food and Drug Administration (FDA).
Clinical Trials for Epilepsy
To learn more about clinical trials for epilepsy and the promise of wearables, Xtalks spoke with Dr. R. Edward Hogan, professor of neurology and director of the Adult Epilepsy Center at Washington University in St. Louis. Dr. Hogan also shared some insights from recent clinical trials for epilepsy he is involved in, including the barriers to patient enrollment and the use of telemedicine.
One clinical trial that Dr. Hogan is involved in is examining the effectiveness of using inhaled alprazolam to treat acute seizures.
“This treatment approach is unique because most medications do not enter the brain fast enough to stop seizures after they start; however, studies with inhaled alprazolam suggest it enters the brain within a minute, possibly earlier, after administration,” explains Dr. Hogan.
Alprazolam is a benzodiazepine. Sold under the brand name Xanax, among others, alprazolam is currently approved by the US Food and Drug Administration (FDA) to treat anxiety disorders and panic disorders with or without agoraphobia (a fear of becoming overwhelmed by anxiety or unable to get help in a specific location or situation).
Patients typically take medications daily to help prevent seizures, but the preventive approach is not completely effective for some patients. Dr. Hogan says that treatment with inhaled alprazolam has the potential to treat seizures after a patient feels one coming on, which would be a major advancement in seizure treatment.
“The hope for this study is to develop a treatment to stop seizures after they start, which would be adjunctive to current therapies, and give patients a much greater sense of control to stop seizures after they begin,” explains Dr. Hogan.
“Because patients with epileptic seizures typically only remember half of their seizures, finding a way to detect and track seizures holds promise. Better tracking of seizures would help treat seizures, especially in tracking response to medications in clinical trials.”
— Dr. R. Edward Hogan, Director of the Adult Epilepsy Center
Another clinical trial that Dr. Hogan is involved with is evaluating a novel drug, currently named LP352, in children and young adults who have rare epileptic encephalopathies, like Lennox-Gastaut syndrome and Dravet syndrome.
Epileptic encephalopathies are severe cases of epilepsy that cause decreased behavioral and cognitive function. In Lennox-Gastaut syndrome, seizures typically start between the ages of two and five, and this rare condition makes up between one to two percent of all epilepsy cases. Dravet syndrome is a rare genetic form where seizures start in the first year of a child’s life.
According to Dr. Hogan, LP352 is different from most other anti-seizure medications because it works by inhibiting a subtype of serotonin receptors in the brain.
“Developing this medication with a different mechanism of action provides hope for better treatment of this group of patients, who typically have very difficult-to-control seizures,” says Dr. Hogan.
Wearable Devices in Clinical Trials for Epilepsy
Although wearable devices with improved seizure detection are being developed, Dr. Hogan explains several difficulties that could be encountered when incorporating wearable devices in clinical trials for epilepsy:
- Seizures may vary considerably between individuals: For instance, heart rate may or may not substantially change during seizures. For patients with relatively minimal heart rate change, seizure detection devices that incorporate heart rate will not be as effective.
- There is a risk of false-positive detections: A false-positive detection occurs when the device indicates that a seizure is happening when in fact the patient is not experiencing one. In some devices used for detecting seizures during sleep, the false-positive detection rate can occur, on average, two times per night. The awakenings at night are often distressing for patients and caregivers, and for some patients in which regular sleep is important for seizure control, could potentially worsen seizures.
- An epileptic seizure is a clinical diagnosis: Currently, FDA regulations require documentation of improvement in clinical seizures to prove that a treatment is effective. The use of information from the wearable device alone is not sufficient to document clinical seizures. The confirmation of the clinical seizure is reported by the patient, or an informed observer.
But refinement of seizure detection devices continues, and Dr. Hogan believes that wearable devices have the potential to be reliably used in clinical trials for epilepsy.
He says that those wearables that are based on evaluating brain waves (through electroencephalogram [EEG] recording) during seizures hold the most promise for reliable detection since brain wave changes are the most direct measure of seizures.
DCT Approaches and Telemedicine
Although Dr. Hogan has not participated directly in a fully decentralized clinical trial (DCT) for patients with epilepsy, he believes that while they offer advantages, they also have significant drawbacks.
“Within trials for epilepsy, there is greater integration into electronic documentation of seizures in an electronic seizure diary, as well as for documentation use in regular study visits,” he says.
One downside of DCTs is that they are challenging for some epilepsy patients, especially those who have difficulty using digital devices.
Regarding virtual and remote care for patients with epilepsy, Dr. Hogan thinks this can offer a substantial benefit for patients, allowing them to complete their visits from home.
It would eliminate the need for transportation, and for patients with mobility issues, it can be especially advantageous.
On the other hand, Dr. Hogan says that many patients prefer in-person visits, which they feel “greatly enhances the quality of communication.” In addition, technological barriers can also pose a significant obstacle for some patients.
Dr. Hogan also emphasizes that virtual/remote care typically only works best in patients with relatively straightforward seizures and associated issues. A second major medical drawback in virtual and remote care is the difficulty in performing an adequate neurological examination.
Wearable devices and DCT approaches have great potential for tracking seizures and enhancing the care of patients with epilepsy; however, the key message from Dr. Hogan is that there is more work to be done to develop reliable wearables and virtual practices for epilepsy treatment and care.
Epilepsy is one of the most common neurological diseases in the world, with around 50 million people worldwide having received this diagnosis. In the US alone, over 3.4 million people have epilepsy, which is a little over one percent of the US population.
Wearable devices for epilepsy are becoming gradually more popular to detect and manage seizures. These devices are designed to help people with epilepsy and their caregivers track seizure activity, provide alerts and help manage medication schedules.
In clinical epilepsy, it can be difficult to evaluate the disease based on patient or caregiver reports and temporary clinical tests. As a result, wearable devices have started to be used in clinical trials for epilepsy to supplement data from self-reported seizure diaries and caregiver reports.
For example, several clinical studies have used Empatica’s Embrace watch to monitor seizure activity and medication adherence. It is also the world’s only wrist-worn wearable for epilepsy that is cleared by the US Food and Drug Administration (FDA).
To learn more about clinical trials for epilepsy and the promise of wearables, Xtalks spoke with Dr. R. Edward Hogan, professor of neurology and director of the Adult Epilepsy Center at Washington University in St. Louis. Dr. Hogan also shared some insights from recent clinical trials for epilepsy he is involved in, including the barriers to patient enrollment and the use of telemedicine.
One clinical trial that Dr. Hogan is involved in is examining the effectiveness of using inhaled alprazolam to treat acute seizures.
“This treatment approach is unique because most medications do not enter the brain fast enough to stop seizures after they start; however, studies with inhaled alprazolam suggest it enters the brain within a minute, possibly earlier, after administration,” explains Dr. Hogan.
Alprazolam is a benzodiazepine. Sold under the brand name Xanax, among others, alprazolam is currently approved by the US Food and Drug Administration (FDA) to treat anxiety disorders and panic disorders with or without agoraphobia (a fear of becoming overwhelmed by anxiety or unable to get help in a specific location or situation).
Patients typically take medications daily to help prevent seizures, but the preventive approach is not completely effective for some patients. Dr. Hogan says that treatment with inhaled alprazolam has the potential to treat seizures after a patient feels one coming on, which would be a major advancement in seizure treatment.
“The hope for this study is to develop a treatment to stop seizures after they start, which would be adjunctive to current therapies, and give patients a much greater sense of control to stop seizures after they begin,” explains Dr. Hogan.
“Because patients with epileptic seizures typically only remember half of their seizures, finding a way to detect and track seizures holds promise. Better tracking of seizures would help in treating seizures, especially in tracking response to medications in clinical trials.”
- Dr. R. Edward Hogan, Director of the Adult Epilepsy Center
Another clinical trial that Dr. Hogan is involved with is evaluating a novel drug, currently named LP352, in children and young adults who have rare epileptic encephalopathies, like Lennox-Gastaut syndrome and Dravet syndrome.
Epileptic encephalopathies are severe cases of epilepsy that cause decreased behavioral and cognitive function. In Lennox-Gastaut syndrome, seizures typically start between the ages of two and five, and this rare condition makes up between one to two percent of all epilepsy cases. Dravet syndrome is a rare genetic form where seizures start in the first year of a child’s life.
According to Dr. Hogan, LP352 is different from most other anti-seizure medications because it works by inhibiting a subtype of serotonin receptors in the brain.
“Developing this medication with a different mechanism of action provides hope for better treatment of this group of patients, who typically have very difficult-to-control seizures,” says Dr. Hogan.
Wearable Devices in Clinical Trials for Epilepsy
Although wearable devices with improved seizure detection are being developed, Dr. Hogan explains several difficulties that could be encountered when incorporating wearable devices in clinical trials for epilepsy:
- Seizures may vary considerably between individuals: For instance, heart rate may or may not substantially change during seizures. For patients with relatively minimal heart rate change, seizure detection devices that incorporate heart rate will not be as effective.
- There is a risk of false-positive detections: A false-positive detection occurs when the device indicates that a seizure is happening when in fact the patient is not experiencing one. In some devices used for detecting seizures during sleep, the false-positive detection rate can occur, on average, two times per night. The awakenings at night are often distressing for patients and caregivers, and for some patients in which regular sleep is important for seizure control, could potentially worsen seizures.
- An epileptic seizure is a clinical diagnosis: Currently, FDA regulations require documentation of improvement in clinical seizures to prove that a treatment is effective. The use of information from the wearable device alone is not sufficient to document clinical seizures. The confirmation of the clinical seizure is reported by the patient, or an informed observer.
But refinement of seizure detection devices continues, and Dr. Hogan believes that wearable devices have the potential to be reliably used in clinical trials for epilepsy.
He says that those wearables that are based on evaluating brain waves (through electroencephalogram [EEG] recording) during seizures hold the most promise for reliable detection since brain wave changes are the most direct measure of seizures.
DCT Approaches and Telemedicine
Although Dr. Hogan has not participated directly in a fully decentralized clinical trial (DCT) for patients with epilepsy, he believes that while they offer advantages, they also have significant drawbacks.
“Within trials for epilepsy, there is greater integration into electronic documentation of seizures in an electronic seizure diary, as well as for documentation use in regular study visits,” he says.
One downside of DCTs is that they are challenging for some epilepsy patients, especially those who have difficulty using digital devices.
Regarding virtual and remote care for patients with epilepsy, Dr. Hogan thinks this can offer a substantial benefit for patients, allowing them to complete their visits from home.
It would eliminate the need for transportation, and for patients with mobility issues, it can be especially advantageous.
On the other hand, Dr. Hogan says that many patients prefer in-person visits, which they feel “greatly enhances the quality of communication.” In addition, technological barriers can also pose a significant obstacle for some patients.
Dr. Hogan also emphasizes that virtual/remote care typically only works best in patients with relatively straightforward seizures and associated issues. A second major medical drawback in virtual and remote care is the difficulty in performing an adequate neurological examination.
Wearable devices and DCT approaches have great potential for tracking seizures and enhancing the care of patients with epilepsy; however, the key message from Dr. Hogan is that there is more work to be done to develop reliable wearables and virtual practices for epilepsy treatment and care.
Photo courtesy of the American Epilepsy Society
ABOUT R. Edward Hogan, MD
Dr. Hogan is the Director of the Adult Epilepsy Center and Professor of Neurology at Washington University in St. Louis. He is also Past President of the American Epilepsy Society.