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Research Update for Toby's Foundation co-sponsored CHF Grant:
Studying the Role of the Gastrointestinal Tract in Canine Epilepsy
Dr. Karen Munana, DVM, MS, DACVIM, North Carolina State University
October 2020
Dr. Munana's research has been extended to January 31, 2022.
Research Update for Toby's Foundation co-sponsored CHF Grant:
Studying the Role of the Gastrointestinal Tract in Canine Epilepsy
Dr. Karen Munana, DVM, MS, DACVIM, North Carolina State University
September 2018
Fecal samples were collected from pairs of dogs, comprised of an epileptic dog that was not being treated with antiepileptic medication and a healthy dog from the same household that was fed the same diet as the epileptic dog.
Seven different species of Lactobacillus were detected. Detailed analysis is currently underway to determine the differential abundance of all microorganisms between the epileptic dogs and controls.
The median concentration of Lactobacillus in the epileptic group was 5.0 log10 CFU/g feces, while the median concentration in the control group was 4.3 log10 CFU/g feces. Statistical analysis is currently being performed to identify any differences in Lactobacillus species and concentrations between the epileptic and control dog pairs.
Antiepileptic medication was not shown to have a negative effect on the growth dynamics of Lactobacillus species.
December 2017
Epilepsy is the most common nervous system disorder of dogs. Approximately one-third of dogs with epilepsy fail to achieve adequate seizure control with anti-seizure medication, and are considered to have drug resistant epilepsy. The investigators hypothesize that dogs with epilepsy have an altered population of Lactobacillus species in their gastrointestinal tracts compared to normal dogs, thus influencing the course of disease. Using molecular genetics and bacterial culture techniques, the investigators will determine differences in bacterial populations, and quantify the Lactobacillus component of the feces of untreated epileptic and control dogs, and determine the effect of antiepileptic medication on Lactobacillus growth rates. Fecal samples were collected from pairs of dogs, comprised of an epileptic dog that was not being treated with antiepileptic medication and a healthy dog from the same household that was fed the same diet as the epileptic dog. In the first experiment, a portion of each sample underwent DNA sequencing and analysis to determine the population of microorganisms present in the samples based on taxonomic classification. The data generated from this experiment is currently undergoing statistical analysis to determine whether differences exist between the epileptic dogs and their normal housemates. The objective of the second set of experiments was to identify and quantify the Lactobacillus component of the fecal samples. The data obtained is currently undergoing statistical analysis to evaluate for differences between the epileptic and control dogs. The final objective of the study is to determine the effect of antiepileptic medication on Lactobacillus growth rates in culture. The Lactobacillus isolates obtained from each fecal sample will be utilized for this experiment. This portion of the study is ongoing.
Research Update for Toby's Foundation sponsored MAF Grant:
Using Accelerometers to Detect Seizures in Dogs
Dr. Karen Munana, DVM, MS, DACVIM, North Carolina State University
December 2017
Idiopathic epilepsy (defined as seizures with no underlying cause) is one of the most common chronic neurological disorders affecting dogs. However, seizure control in dogs can be difficult, often hindered by an inability to accurately measure seizure frequency and duration. Inadequate seizure control poses not only a financial burden, but also is an emotional burden for families caring for affected dogs, leading to care-giver fatigue, impaired quality of life, and sometimes to euthanasia of the affected dog. The research team fits dogs diagnosed with idiopathic epilepsy with accelerometers (Whistle Activity Monitors) designed especially for dogs, then measure activity levels. Owners keep a log of seizure activity, and cameras are installed in homes to record activity measured during an owner's absence. To date, 20 dogs have been enrolled, with 10 completing the study. Six dogs currently are enrolled with three dogs withdrawn for a variety of reasons, including uncontrolled seizure activity. While this study is ongoing with continued enrollment of dogs, the team has successfully documented the detection of seizure activity using the device. Analysis of the data at the completion of the study will determine the accuracy of the device in detecting seizures.
February 2016
TOBY'S FOUNDATION is Giving $10,000 for a New Canine Epilepsy Research Study
Toby's Foundation is pleased to announce that we are giving $10,000 to co-sponsor a Morris Animal Foundation (MAF) grant for Dr. Karen Munana at North Carolina State University College of Veterinary Medicine (NCSU-CVM).
Grant information:
The Research Study: Improving seizure monitoring in dogs with epilepsy
Scientific Title: Use of Accelerometry to Detect Seizure Activity in Dogs with Idiopathic Epilepsy
Summary: Researchers will investigate the use of a commercially available, collar-mounted activity monitor to detect seizures in dogs with epilepsy.
Description: Epilepsy is a common problem in dogs that typically requires lifelong medical attention. However, the majority of dogs do not become seizure-free with treatment, and a consistent worry for caregivers is the risk of seizures occurring when a dog is alone. Researchers will evaluate the use of a commercially available, collar-mounted accelerometer to reliably detect seizure activity in epileptic dogs. The availability of an easily worn, inexpensive device to detect seizures will provide valuable data to help veterinarians make informed treatment adjustments, and reduce the risk of injury or death from unobserved seizures for their canine patients.
Testing Requirements: Dogs with idiopathic epilepsy that are experiencing an average of 3 or more generalized seizures per month despite appropriate treatment; Age at onset of seizures is 6 months to 6 years, with 1 year documented history if seizures; owners must have access to a Smartphone and a wireless internet in their home; owners must be willing to travel to NC State University College of Veterinary Medicine for 3 study-related visits over a 6 month period.
Contact Information:
Julie Ann Nettifee RVT, BS, VTS (Neurology)
North Carolina State University
College of Veterinary Medicine
Department of Clinical Sciences & Comparative Medicine Institute
919-513-6812 Phone
919-513-6830 FAX
- Companion Animal Epilepsy
- Comparative Medicine Institute
- Julie Nettifee, RVT, BS, VTS (Neurology) - Profile
August 2016
Clinical Trial Recruitment:
For a study by Dr. Karen Munana, DVM, North Carolina State University - College of Veterinary Medicine
The Research Study: The Microbiota-Gut-Brain axis in canine epilepsy-Determining the role of Lactobacilli
Description: This study aims to evaluate the role of certain intestinal bacteria in the management of epilepsy in dogs. Alterations in the population of intestinal bacteria in the Lactobacillus group are believed to play a role in the development and progression of several human diseases of the nervous system. An association between epilepsy and both celiac disease and inflammatory bowel disease has been identified in humans, which suggests that changes in intestinal bacteria might also play a role in the progression of epilepsy. The purpose of this trial is to evaluate bacterial populations in the gastrointestinal tract of dogs with epilepsy and compare these to normal dogs. We hypothesize that dogs with epilepsy have alterations in the population of lactobacillus as compared to normal dogs. This study will provide preliminary information on the role of GI tract bacteria in canine epilepsy, and further our understanding to help us develop more successful outcomes for this disorder.
Testing Requirement: We are recruiting dogs that have been diagnosed with epilepsy but are not currently receiving anti-seizure medication, and that live in a household with another dog that is not epileptic. Owners of dogs enrolled in the study will be instructed to collect a fresh stool sample from their dogs to ship to the investigators. Owners will also be asked to complete a brief questionnaire related to their dog's environment, diet and health. Dogs will received a fecal exam at no-charge to the owner. All study results will be provided to owners and their family veterinarians.
Your dog does not have to go to NCSU-CVM for this study so if your dog meets the above requirements for participation in this study please contact Julie Nettifee. See the contact information below.
Contact Information:
Julie Ann Nettifee RVT, BS, VTS (Neurology)
North Carolina State University
College of Veterinary Medicine
Department of Clinical Sciences & Comparative Medicine Institute
919-513-6812 Phone
919-513-6830 FAX
- Companion Animal Epilepsy
- Comparative Medicine Institute
- Julie Nettifee, RVT, BS, VTS (Neurology) - Profile
Research News for Dr. Karen Munana
April 2015
A study "Effect of Chronic Administration of Phenobarbital, or Bromide, on Pharmacokinetics of Levetiracetam in Dogs with Epilepsy" supported by a grant from Toby's Foundation for Dr. Karen Munana has been published in The Journal of Veterinary Internal Medicine.
Veterinary neurology experts collaborate for first ever global consensus on pets with epilepsy
September 2015
An international body of vets and scientists have come together to set out unified and standardised guidelines for the research, diagnosis and treatment of canine and feline epilepsy for the first time ever in veterinary medicine. The International Veterinary Epilepsy Task Force (IVETF) has developed common language to be used in the 'chain of care' of canine and feline epilepsy.
February 2012
This study was undertaken to determine whether the metabolism of the anti-seizure drug levetiracetam (LEV) varies depending on whether it is given in combination with phenobarbital and/or potassium bromide to dogs with epilepsy. Dogs previously diagnosed with epilepsy that were being treated with LEV in addition to phenobarbital, potassium bromide or both were studied. Blood samples were collected at 5 time points within a 6-hour period for measurement of LEV levels. The study demonstrated that there is considerable variability in blood levels of LEV among dogs that are receiving LEV as a treatment for epilepsy. The group of dogs being administered LEV and bromide in combination tended to have the highest blood LEV levels, followed by the group receiving LEV and phenobarbital in combination, while the group receiving LEV, phenobarbital and bromide in combination tended to have the lowest blood LEV levels. This suggests that the administration of phenobarbital, with or without bromide, might affect the metabolism of LEV when the drugs are used together to treat epilepsy in dogs. Based on the study results, it is recommended that LEV blood levels be measured in dogs that are receiving LEV in combination with other drugs, particularly if adequate seizure control is not achieved. Additional studies are required to determine a recommended target LEV range in dogs that is associated with seizure control.
This study can advance more effective treatments for dogs suffering from canine epilepsy. There is more detailed information that will become available after the study is published.
North Carolina State University has a survey they would like filled out by owners of pets with epilepsy on The Impact of Epilepsy in Companion Animal Patients. Please see below.
September 2011
Dear Pet Owner:
Seizures affect more than 5 percent of the companion animal population. We are contacting you today to see if you might be willing to share with us some information regarding your experiences with a pet with epilepsy so that we, as the veterinary profession, can develop a greater understanding of your needs living with a pet with epilepsy. Information obtained from this survey will help us to: Increase our understanding of the disease impacts, help us to provide more information to potential grantors to study the disease as it relates to impacts on the owner, and more.
All of the personal information provided will remain confidential. We appreciate your consideration of this request. The survey can be accessed at the followiing URL: Click Here
If you have any questions whatsoever regarding this survey, please contact Julie Nettifee Osborne, RVT, BS, VTS (Neurology): julie_osborne@ncsu.edu or 919-513-6812.
Warm Regards,
Julie
Julie Ann Nettifee Osborne, RVT, BS
North Carolina State University
College of Veterinary Medicine
Department of Clinical Sciences
1060 William Moore Drive
Raleigh, NC 27607
919-513-6812 Phone
919-513-6830 FAX
Recruiting Dogs for New Anticonvulsant Research
February, 2010
Julie Nettifee Osborne from North Carolina State University tells us that a new anticonvulsant has been developed by a major veterinary pharmaceutical company.
We are recruiting dogs that are not on any anticonvulsants at this time. Feel free to post the following link on your website, www.helpfordogswithseizures.com The study is nationwide and selection criteria and study information are listed on this link.
As for the Keppra study and the MDR study, they have both been completed, and we are in the process of writing up the results for presentation at the ACVIM forum in June. According to Dr. Munana, we should be able to share the results with them within the next few months, and would appreciate them posting the information on their website.
Other studies that are underway include a clinical study of Keppra Pharmacokinetics when given in combination with Phenobarbital. We actually still need a few dogs to participate that are on Phenobarbital at steady state levels, and Keppra. They do not have to come to NCSU-CVM, we can potentially arrange for sampling to be done and shipped to us from a referring DVM or Neurologist.
June 2010
Dr. Karen Munana presented her finding on the two studies EVALUATION OF LEVETIRACETAM AS ADJUNCTIVE TREATMENT FOR CANINE EPILEPSY and ASSOCIATION BETWEEN THE ABCB-1 (MDR-1) GENE AND SEIZURE CONTROL IN CANINE EPILEPSY at the American College meeting in Anaheim, CA on June 12, 2010. Below are the summaries from her findings.
EVALUATION OF LEVETIRACETAM AS ADJUNCTIVE TREATMENT FOR CANINE EPILEPSY
Principal Investigator: Dr. Karen R. Munana, North Carolina State University College of Veterinary Medicine
Funding: Morris Animal Foundation
The purpose of this blinded, placebo controlled clinical trial was to evaluate the safety and effectiveness of levetiracetam when used as add-on therapy in dogs with poorly controlled idiopathic epilepsy. Findings from the study suggest that levetiracetam is safe in epileptic dogs. There was no difference in incidence of side effects between levetiracetam and placebo treatment, and no changes in laboratory parameters were identified throughout the course of the study. The majority of dogs experienced a decrease in seizure frequency during levetiracetam treatment. However, the weekly seizure frequency relative to baseline decreased during both levetiracetam and placebo administration, such that a significant difference in effectiveness of levetiracetam over placebo was not observed. Levetiracetam serum levels were highly variable and did not correlate with treatment response. Further evaluation of levetiracetam as therapy for canine epilepsy is warranted.
ASSOCIATION BETWEEN THE ABCB-1 (MDR-1) GENE AND SEIZURE CONTROL IN CANINE EPILEPSY.
Principal Investigator: Dr. Karen R. Munana, North Carolina State University College of Veterinary Medicine
Funding: Collie Health Foundation
Medically refractory seizures are a significant problem in both human and canine epilepsy. Alterations in the ABCB-1 (also known as the multidrug resistance or MDR-1) gene have been proposed to play a role in drug-resistant epilepsy. The ABCB-1 mutation results in loss of function of p-glycoprotein, a protein responsible for pumping compounds out of the brain. The aim of this study was to determine whether differences in the ABCB-1 gene are associated with seizure control in canine epilepsy. Collies, a breed known to have a high incidence of mutation of the ABCB-1 gene, were studied. Epileptic dogs with the mutation were significantly more likely to have good seizure control and to be treated with fewer antiepileptic medications than epileptic dogs that were carriers of the mutation or that had the normal genotype. These findings suggest that p-glycoprotein may influence seizure severity in epileptic dogs. Further study is needed to determine whether this is a manifestation of the initial seizure disorder or reflects a response to treatment.
For further information, please contact animalepilepsy@ncsu.edu.
October, 2010
Toby's Foundation Awards its First direct Grant to Dr Karen Munana at North Carolina State University and Dedicates it in Memory of Sheila Dolan
Pam Douglas, President of Toby's Foundation say, we can now sponsor grants under $10,000 for canine epilepsy research. This is an important step for us in the fight against canine epilepsy. Our mission is to stop canine epilepsy by supporting research to find the gene(s) responsible and develop a screening test and to support research for more effective treatments for dogs affected by this disease.
Dr. Munana's grant is for one year and will investigate The Pharmacokinetics of Levetiracetam in Epileptic Dogs When Used Concurrently With other Antiepileptics. The award is for $5,276.00. For larger grants we can continue to co-sponsor studies such as the one we currently have with the Canine Health Foundation (CHF) for Dr. Ned Patterson's Aussie epilepsy study at UMN, Grant #748 SNP Association Mapping for Canine Epilepsy.
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Dr. Munana presented two studies at the American College of Veterinarians in Internal Medicine (ACVIM) in June 2010 in Anaheim, CA . Please click on the link below to go to our Research page and read summaries from Dr. Munana on these two studies regarding more effective treatments for dogs affected by canine epilepsy. It is estimated that as many as 25% of the dogs affected with the disease have refractory seizures meaning they do not respond well to traditional treatments and their seizures are not well controlled.
Pam Douglas met with Dr. Karen Munana at the ACVIM meeting in Anaheim , CA to discuss with her about our newly awarded grant for her research and her two preceding studies. Pam Douglas also met with Dr. Ned Patterson of UMN at the ACVIM meeting to discuss Aussie canine epilepsy research and a new grant in 2011 to keep Aussie epilepsy research moving forward.
December, 2010
A few more dogs with epilepsy are needed for a new study. Can you help? For information on this new study and contact information to see if your dog can help by participating please see below. All blood levels will be provided to the owners at no charge.
Dogs would not necessarily have to go to NCSU-CVM, as long as the referring DVM is willing to help obtain samples.
NEW!! Canine Keppra Pharmacokinetic Study III: Recruiting Open, July 2010
Recruitment is open for dogs with epilepsy that are being treated with Keppra (levetiracetam) and Phenobarbital (group I) Keppra and Potassium Bromide (group II) , or Keppra, Phenobarbital and Potassium Bromide (group III) for a Pharmacokinetic study. This study is being conducted at North Carolina State Unversity-College of Veterinary Medicine, under the direction of Dr. Karen Munana, DVM, DACVIM (Neurology).
If your dog has been diagnosed with epilepsy, and is receiving the drugs listed above in any of the 3 groups listed, we are interested in sampling your pet to determine how Keppra interacts with the other anticonvulsants through sequential blood sampling in a one-day study. All blood levels will be provided to the owners at no-charge. If you are interested in more information regarding this project, or to see if your pet qualifies, please contact Julie Osborne, julie_osborne@ncsu.edu or 919-513-6812. We would like to thank Toby's Foundation for their assistance in the funding of this important project.
Julie Nettifee Osborne, RVT, BS
North Carolina State University
College of Veterinary Medicine
Department of Clinical Sciences
4700 Hillsborough Street
Raleigh, NC 27606
919-513-6812 Phone
919-513-6830 FAX
North Carolina State University has sent us the following information regarding their epilepsy research.
Click here to read the full press release.
August 2007
Pamela:
I have attached some information that you may include on your website or in newsletters, but in short, we are recruiting for the following:
1. Collies, Shelties and Australian Shepherds for the MDR-1 study (click here for specifics). As long as pet owners are able to provide a copy of a recent anticonvulsant level that is in therapeutic range, we will send them brushes for MDR testing that will be performed at no cost to the owner. Results of the testing will be provided to each owner.
2. Dogs with Refractory Epilepsy (At least 4 seizures/month) are being recruited for an extension of the Keppra Drug study. Dogs for this study will have to travel to NCSU-CVM or the University of Tennessee approximately 7-8 times over a 44-week period.
For information regarding the above 2 studies, contact julie_osborne@ncsu.edu.
3. Blood samples from epileptic dogs are still being requested for a genetic study on canine epilepsy. For more information on this study contact carolinacanineepilepsy@gmail.com
Thanks for all you do to help out pets and their owners!
Warm Regards,
Julie Nettifee Osborne, RVT, BS
NCSU-CVM