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

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.

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.

Positive airway pressure therapy improved seizure control in epileptic patients with obstructive sleep apnea

Sleep study, “1145 Long-Term Seizure Control in Epileptic Patients with Obstructive Sleep Apnea Using Positive Airway Pressure Therapy” found [1]:

[There were] better 1-year seizure outcomes in people with epilepsy and Positive Airway Pressure-treated Obstructive Sleep Apnea compared with Untreated Obstructive Sleep Apnea and No Obstructive Sleep Apnea.

[Researchers] investigated the effect of positive airway pressure therapy on long-term seizure outcomes in adults with epilepsy who underwent polysomnography at Cleveland Clinic (1997–2016). Seizure outcomes included mean % seizure reduction, ?50% seizure reduction from baseline (%, responder rate), and ? 50% seizure reduction or seizure free at both baseline and follow up (%, successful outcome).

Successful outcome was achieved more often in Positive Airway Pressure-treated (84%) than Untreated Obstructive Sleep Apnea (57%; p=0.002) or No Obstructive Sleep Apnea (66%; p=0.009) groups. [The results] expand existing literature supporting the impact of sleep therapies on seizure control in people with epilepsy.

Fenfluramine provides significant seizure reduction in Dravet syndrome, according to European Journal of Neurology study

The study “Low-dose fenfluramine significantly reduces seizure frequency in Dravet syndrome: a prospective study of a new cohort of patients” found [1]:

Patients with Dravet syndrome experienced sustained periods of clinically meaningful improved seizure control during fenfluramine treatment with a favorable tolerability and no echocardiographic or clinical evidence of cardiac valvulopathy or pulmonary hypertension.

Nine patients (aged 1.2–29.8 years) enrolled in the study and were treated with fenfluramine for a median duration of 1.5 (range, 0.3–5.1) years.

All patients demonstrated a reduction in seizure frequency during the treatment period with a median reduction of 75% (range, 28–100%). Seven patients (78%) experienced a ?50% reduction in major motor seizure frequency.

FDA Approves Lundbeck’s New Drug

The Food and Drug Administration (FDA) has approved Lundbeck’s Carnexiv™ (carbamazepine) injection as a short-term replacement therapy for oral carbamazepine formulations in adults with certain seizure types when oral administration is temporarily not feasible. Carnexiv will be the first available intravenous (IV) formulation of the antiepileptic drug (AED) carbamazepine, and Lundbeck plans to make it commercially available in the US in early 2017. Carnexiv is a short-term (7 days) intravenous replacement therapy for oral carbamazepine formulations that provides continuity of care for adult patients who are unable to take carbamazepine by mouth and have seizure types: partial seizures with complex symptomatology; generalized tonic-clonic seizures; and mixed seizure patterns.

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CURE Responds to DEA’s Decision on Marijuana Scheduling

Chicago, IL – This month the Drug Enforcement Administration (DEA) announced their decision to maintain marijuana as a Schedule I drug, despite petitions from Citizens United for Research in Epilepsy (CURE) and many other research and patient-focused organizations concerned with the federal barriers prohibiting researchers from fully understanding the potential of medical cannabis. Despite this setback, CURE is pleased with the DEA’s decision to expand the number of DEA-registered marijuana manufacturers for research, of which there is currently only one, so more researchers will be able to conduct much-needed research on cannabidiol (CBD) – the major non-psychoactive ingredient in marijuana, as well as the many other cannabinoids found in marijuana.

An estimated 3 million Americans currently live with epilepsy and for two-thirds of them, the cause is unknown, making treatment difficult if not impossible to pinpoint. The positive results that some people with epilepsy have been seeing from CBD-rich marijuana extracts are giving so many parents what they have been lacking for so long – hope. CBD may not be the answer for all of these families, but when available medications and surgeries do not stop the uncontrollable seizures, every avenue must be explored.

As the leading nongovernmental agency fully committed to funding research in epilepsy, we believe researchers should be encouraged and supported to test not only pure CBD, but also high CBD/low-THC cannabis, pure-THC and other types of medical marijuana to determine the efficacy of these and other combinations on seizure control and the genesis of epilepsy. We are hoping for more changes to marijuana access that makes it easier for researchers to continue their vital work.

The Fight to Improve Research Access to Cannabis Continues

WASHINGTON, D.C.— Due to its incredible medicinal potential, we continue to believe that more research must be done on marijuana rich in cannabidiol (CBD). In late April, CURE signed a group letter addressed to Chuck Rosenberg, the head of the Drug Enforcement Administration (DEA), urging him to remove cannabis from Schedule I in the Controlled Substances Act.

This would eradicate federal barriers to research, paving the way for more progressive research and new treatments. CURE has joined with other organizations in support of the Compassionate Access, Research Expansion, and Respect States Act (CARERS, S. 683, H.R. 1538) which would facilitate safe and legal access to medical cannabis for patients and physicians acting in accordance with state law and lift federal barriers to research. The CARERS Act would also remove low-THC cannabis from the CSA allowing individuals in states that have created protections for low-THC therapies to more easily access this potential treatment option.

Current regulatory hurdles make it difficult for researchers to gain access to marijuana rich in CBD. There is no debate that the hoops through which researchers must jump to acquire marijuana, or any chemical found in it, are hindering scientific advancement—and CURE is committed to helping researchers overcome these obstacles to advance research in this important area.

Acorda Therapeutics, Inc. Announces Discontinuation of PLUMIAZ™ (diazepam)

WASHINGTON, D.C.— Acorda Therapeutics, Inc. announced May 20 it will discontinue development of PLUMIAZ™ (diazepam) Nasal Spray, an investigational therapy which was being studied for the treatment of seizure clusters in people with epilepsy. Data from ongoing clinical trials do not demonstrate its bioequivalence to Diastat® gel, which is needed for New Drug Applications (NDA).

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