Clobazam Clinical Trial: Use for Epilepsy and Anxiety

This study is an open label, adjunctive, proof of concept, pilot clinical trial. Pediatric patients with epilepsy and clinically significant anxiety will be recruited and if enrolled will receive active treatment, involving flexible dose titration of clobazam and will be monitored for a period of four months. The study will be monitored and overseen by the Johns Hopkins Hospital Institutional Review Board.

Eligibility Criteria

Ages Eligible for Study: 6 Years to 17 Years (Child)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No

Inclusion Criteria:

  • Established diagnosis of epilepsy, characterized by focal seizures with suspected or documented localization in the temporal lobe. All participants will have active epilepsy that requires treatment with anticonvulsant medication.
    • Although it is not necessary to be seizure free, a seizure baseline period will be established in the 60 days prior to enrollment into the study.
    • Current regimen of anticonvulsant drugs must have been stable for 30 days prior to entry into the study.
  • No episodes of seizure clusters of status epilepticus within 30 days prior to entry into the study.
  • Established symptoms of anxiety with functional impairment.
  • Baseline behavioral criteria for inclusion will include subscale scores above the norm for age and gender on one of the following:
    • Pediatric Anxiety Rating Scale (PARS).
    • Multidimensional Anxiety Scale (MASC)
  • Male or female participants equal to or above age 6 and below age 18 at the start of the study. No exclusion will be made on the basis of gender or minority status.
  • Good general health as determined by medical history and physical examination.
  • Ability to swallow pills (participant will receive pill swallowing instruction if necessary). The medicine may be cut into pieces and/or mixed with applesauce.
  • If female of childbearing age, a negative urine or serum pregnancy test must be established or assured at baseline. Additionally, the participant must agree to use abstinence or appropriate contraception methods or be otherwise incapable of pregnancy for the duration of the study. Pregnancy test results will be shared with parent or guardian. Pregnancy status (or prevention) and abstinence or contraception methods will be addressed throughout the study for females of childbearing age as well as for post-pubertal males.
  • Previous subjects who failed at any point to meet continuation criteria and withdrew early may be considered for re-enrollment by the PI on a case-by-case basis.
  • Participant or legal caregiver capable of providing informed consent and fully capable of monitoring the subject’s disease process and compliance with treatment.

 

Exclusion Criteria:

  • Previous allergic or hypersensitivity reactions to Onfi® or benzodiazepines
  • Active substance abuse or dependence within 30 days of enrollment
  • DSM-V diagnosis of psychotic illness or imminent risk of harm to self or others.
  • Current use of antidepressants
  • Current standing use of benzodiazepines (except as “rescue” medicine)
  • Serious or unstable medical or neurologic conditions such as HIV, liver or kidney disease, cancer or diabetes.
  • Participation in a previous experimental drug study within 30 days of baseline visit.
  • Estimated IQ<70 as indicated by initial clinical assessment (rendering rating scales invalid)
  • Insufficient capacity of caregiver or legal guardian to understand and appropriately consent for study procedures

Personalized epilepsy seizure prediction a possibility with AI, according to EBioMedicine report

According to research findings, “Epileptic Seizure Prediction Using Big Data and Deep Learning: Toward a Mobile System” [1]:

Deep learning in combination with neuromorphic hardware can provide the basis for a wearable, real-time, always-on, patient-specific seizure warning system with low power consumption and reliable long-term performance.

Harnessing the recent breakthroughs in deep learning techniques and in building specialized processing chips, [researchers] have demonstrated that seizures can now be predicted by a portable device. [The] system automatically learns patient-specific pre-seizure signatures, and, in real time, warns of oncoming seizures.

Data for the study were collected for a previous clinical trial of an implanted seizure advisory system. This study may serve as a benchmark for new work exploring deep learning enabled seizure prediction.

Vigabatrin evaluated for focal seizures in tuberous sclerosis in recent study

A study, “Vigabatrin for focal seizures in tuberous sclerosis,” found that [1]:

Vigabatrin (VGB) is used for focal seizures in tuberous sclerosis (TS) and may be an effective therapy in patients who fail to respond adequately to other anti-seizure medications while awaiting definitive epilepsy surgery.

Vigabatrin is well-established as the first-line therapy for infantile spasms in association with tuberous sclerosis, but less is known about its role in focal seizures due to tuberous sclerosis.

[Researchers] retrospectively identified 22 patients with tuberous sclerosis who received Vigabatrin for focal seizures, starting Vigabatrin in June 1989 and continuing through the present time. Nineteen (86%) had a history of infantile spasms and all except the two oldest, born in 1986, received Vigabatrin for infantile spasms. Eleven of these individuals exhibited improvement in or resolution of infantile spasms. Sixteen out of 17 with infantile spasms remained on Vigabatrin to treat focal seizures.

The risk for vision loss due to photoreceptor toxicity continues to limit prolonged use.

Novel fMRI applications could help map language prior to epilepsy surgery

According to the study, “Novel Data-Driven Method for Language Dominance Derived from Resting-State and Language Task fMRI Functional Connectivity in Epilepsy Patients” [1]:

[Researchers] demonstrated the potential of using [their] novel data-driven method to parse the language network and establish reliable language laterality in task-free fMRI as well as task fMRI.

Presurgical language mapping is crucial to help evaluate the risk of postoperative deficits for epilepsy surgery. While fMRI provides a non-invasive method for this, task compliance is difficult for very young or intellectually impaired patients to obtain reliable activations.

[These results] may help expand the use of clinical fMRI because a successful study would no longer depend upon task performance of the epilepsy patient, opening its utility up to younger and more impaired populations.

Study evaluates long-term health impact of convulsive seizures in children

According to a Lancet study, “Long-term prognosis after childhood convulsive status epilepticus: a prospective cohort study” [1]:

Childhood convulsive status epilepticus (CSE) is associated with substantial long-term neurological morbidity, but primarily in those who have epilepsy, neurological abnormalities, or both before the episode of convulsive status epilepticus. Survivors without neurological abnormalities before convulsive status epilepticus have favorable outcomes.

[Researchers] collected data from structured clinical neurological assessment, neurocognitive assessment (Wechsler Abbreviated Scale of Intelligence), brain MRI, medical records, and structured interviews with participants and their parents to determine neurological outcomes, with adverse outcome defined as presence of one or more of epilepsy (active or in remission), motor disability, intellectual disability, or statement of special educational needs.

Presurgical imaging may predict whether epilepsy surgery will work

According to, “A Hierarchical Bayesian Model for the Identification of PET Markers Associated to the Prediction of Surgical Outcome after Anterior Temporal Lobe Resection,” a study in Frontiers in Neuroscience [1]:

[Researchers] have identified a subgroup of temporal lobe epilepsy patients at high risk for post-surgical seizure recurrence after anterior temporal lobe resection.

[The study] developed an integrative Bayesian predictive modeling framework that identifies individual pathological brain states based on the selection of fluoro-deoxyglucose positron emission tomography (PET) imaging biomarkers and evaluated the association of those states with a clinical outcome.

[The study] shows that the proposed method achieves high cross-validated accuracy in predicting post-surgical seizure recurrence.

Study analyzes association of antiepileptic drugs and suicidality

According to a study, “A Temporal Evaluation of Antiepileptic Drugs and Suicidality: Is it the Medication or the Comorbidity?” [1]:

While individuals with antiepileptic drug exposure had higher likelihood of suicide related behavior, the trend started before the antiepileptic drug exposure and was not differentially associated with epilepsy status or antiepileptic drug type received.

[The study] compared trends of suicide related behavior before and after initiation of antiepileptic drug therapy among antiepileptic drug users with and without epilepsy to individuals without antiepileptic drug use controlling for sociodemographic characteristics and mental health comorbidity.

Given the limited information available on depression severity in this administrative data it is possible that the significant effect for antiepileptic drug exposure is due to residual confounding of mental health comorbidity.

Vagus nerve stimulator placement, corpus callostomy, or ketogenic diet initiation could help children with pharmacoresistent epilepsy

According to a study, “Seizure control and quality of life in children with epilepsy after vagus nerve stimulator placement, corpus callostomy, or ketogenic diet initiation” [1]:

Vagus nerve stimulator placement, corpus callostomy, and ketogenic diet was successful in reducing both generalized and focal seizure types, [with] ketogenic diet showing a trend towards slightly better success.

Parents of 210 patients, who had 292 (VNS, n=150; CC, n=44; KD, n=98) treatment modalities, agreed to participate in a phone interview. 60% were male with ages ranging from 8 months to 20 years. Seizure control, cognitive and behavioral factors, quality of life and treatment satisfaction was rated via a 9-item telephone questionnaire.

Improvements observed in cognitive and behavioral domains, better seizure control and less falls positively affected quality of life. Parent overall satisfaction was greater than 75%, which far outweighed seizure reduction or behavioral improvements.

These findings support palliative management for those with pharmacoresistant epilepsy who are not candidates for surgical resection.

CURE Taking Flight and Innovator Awards accepting applications

CURE is now accepting LOIs for its first 2018 grant cycle. These grants include:

  • Innovator Award – A grant of $50,000 paid over one year
  • Taking Flight Award – A grant of $100,000 paid over one year

 

The deadline for both of these grants is January 8, 2018 at 9pm Eastern.

Full Key Cycle 1 timeline details are below:

Activity Date
Letter of Intent Deadline Monday, January 8th, 2018 – 9pm ET
Full Application Invitations Wednesday, February 21st, 2018
Full Application Deadline Wednesday, March 28th, 2018 – 9pm ET
Anticipated Award Announcement July 2018
Anticipated Project Start Date September 2018

 

For more information or to apply, interested parties should visit CURE’s Grant Opportunities webpage.