Comparison of Clorazepate and Levetiracetam as Pulse Therapy for the In-Home Management of Cluster Seizures in Dogs with Idiopathic Epilepsy: A Pilot Study

Idiopathic epilepsy is the most common chronic neurological disorder in dogs. Approximately half of all dogs with idiopathic epilepsy have cluster seizures, defined as 2 or more seizures within a 24-hour period. Cluster seizures are considered a medical emergency, as dogs with cluster seizures are at increased risk of both medical complications and death. Therapeutic regimens are commonly prescribed that include in-home administration of emergency medication for cluster seizures, but there is a lack of evidence on which to base those treatment recommendations.

The aim of this pilot study is to evaluate and compare the use of two oral treatment protocols for the in-home management of cluster seizures in dogs with idiopathic epilepsy. The researchers hypothesize that an in-home emergency treatment protocol that includes intermittent, or pulse therapy, with either oral clorazepate or oral levetiracetam is effective in controlling cluster seizures in dogs with idiopathic epilepsy. Thirty idiopathic epileptic dogs with a history of cluster seizures will be enrolled in this randomized clinical trial. Dogs will receive oral pulse therapy with either clorazepate or levetiracetam, in combination with intranasal midazolam, for the in-home emergency treatment of cluster seizures. Owners will record data on seizure frequency, medication administered, and adverse effects. The primary outcome measurement will be the number of dogs that respond with no additional seizures over a 24-hour period.

The information gained from this study will help guide treatment recommendations for cluster seizures and serve as a basis for future studies, with the goal of improving management strategies for cluster seizures in dogs with idiopathic epilepsy.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 03243-A

RESEARCHERS

Karen Munana, DVM, MS; North Carolina State University

Amount: $4,000

Efficacy of Cannabidiol (CBD) for the Treatment of Canine Epilepsy

Epilepsy is the most common neurologic condition in dogs. Approximately 20-30% of dogs receiving standard therapy remain uncontrolled for their seizures. Additionally, the side effects of the antiepileptic drugs (AED) are often unacceptable. Thus, there is a need for an AED that is efficacious with minimal side effects. Cannabidiol (CBD), a prominent non-psychotropic component of the Cannabis sativa plant, has been shown to have anti-convulsant properties. While CBD offers promise as a treatment for canine epilepsy, controlled studies are needed to prove its effectiveness.

In this randomized, double-blinded, placebo-controlled, crossover clinical trial, client-owned dogs with uncontrolled epilepsy will be enrolled following a full seizure evaluation, including bloodwork and magnetic resonance imaging. The canine patients will first receive either a placebo or CBD in addition to their standard AED protocol and then the opposite drug in this crossover designed study. Seizure frequency and medication side effects will be monitored by owners using a seizure log and questionnaire. Regular CBD plasma concentrations, routine bloodwork and serial physical examinations will be monitored by the investigator.

The primary goal of the study is to determine the efficacy of CBD in the treatment of canine epilepsy. If CBD is effective in decreasing seizure frequency, it has the potential to improve the quality and length of life for dogs with uncontrolled epilepsy, and add a much-needed tool for veterinarians in the treatment of canine epilepsy.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02323

RESEARCHERS

Stephanie McGrath, DVM, MS; Colorado State University
Amount: $10,000

Identification of Genetic Risk Factors for Canine Epilepsy

Epilepsy is one of the most common neurologic diseases of dogs and a top concern of dog breeders. Despite strong evidence that genetics is important in determining the risk of idiopathic epilepsy, numerous gene mapping studies have failed to identify a locus that accounts for that risk in either dogs or humans.

Seizures occur when excessive activity goes beyond the normal threshold for brain function, many factors contribute to that level of activity, and therefore, mutations in numerous genes may collectively contribute to increased activity until that threshold is exceeded, resulting in epilepsy. Any one of these mutations may be present in non-epileptic dogs, but because it only partially alters activity, it would not produce seizures. Therefore, traditional gene mapping studies might overlook that mutation.

Using a novel whole genome sequencing approach the investigators hope to identify DNA variations in epileptic dogs that could affect the function of genes such as ion channels and neurotransmitter receptors that have been shown to alter the seizure threshold in humans or rodents. The frequency of such variations in populations of epileptic and non-epileptic dogs will be directly compared rather than the indirect markers used in traditional mapping studies. The increased power provided by looking for specific gene candidate variations rather than linked markers will aid the identification of epilepsy risk factors, perhaps leading to development of DNA tests to enable breeders to select against such risk factors.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: CHF-02257

RESEARCHERS

Dr. Gary S. Johnson, DVM PhD
University of Missouri, Columbia
Amount: $2,000

Investigating a Ketogenic Medium-Chain Triglyceride (MCT) Supplement for the Treatment of Drug-Resistant Canine Idiopathic Epilepsy and Its Behavioral Comorbidities

Canine epilepsy is a chronic neurological condition, often requiring lifelong medication with antiepileptic drugs (AEDs). Despite appropriate treatment with available AEDs, seizure freedom may not always be achievable. Indeed, over two thirds of dogs with epilepsy continue to have seizures long-term and around 20-30% remain poorly controlled on standard AEDs. The hardest to treat dogs are termed ‘refractory’ or ‘drug-resistant’ patients.

There is an urgent need to develop alternative treatments to improve the quality of life (QoL) of drug-resistant patients. The ketogenic diet, originally characterized as high in fat and low in carbohydrates, has been a successful treatment in children with epilepsy for several decades, decreasing seizure activity and even leading to seizure freedom in drug-resistant patients. Recent research has identified that a component of the ketogenic diet, a medium-chain fatty acid (MCT) called C10 has direct anti-seizure effects on the brain.

The investigators will assess whether dietary supplementation with ACT oil containing C10 for dogs with drug-resistant epilepsy will reduce seizure frequency and/or severity. As epilepsy has multiple impacts on QoL beyond seizure frequency, the researchers will also investigate whether the MCT supplement alters the side effect profile of AEDs, improves behavioral problems associated with epilepsy (e.g. anxiety) and cognition, and improves the stress levels of the affected dog. If successful, MCT supplements could provide a new tool for canine epilepsy treatment

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02252

RESEARCHERS

Dr. Holger Andreas Volk, DVM, PhD
Royal Veterinary College, University of London
Amount: $2,000