The Effects of Canine MDR1 Mutation on Common Pre-anesthetic Medication Combinations

Species: 
Dog
Area of Study: 
Anesthesiology

Purpose of Study: 

There is a gene mutation (ABCB1-1Δ or MDR1) in dogs that results in an increase in sensitivity  to certain drugs, including several drugs used for anesthesia/analgesia. The most common dog breeds that carry this gene mutation include: Collie, Longhaired Whippet, Shetland Sheepdog, Australian Shepherd (and miniature), Waller, White Swiss Shepherd, Old English Sheepdog, Border Collie. However, multiple studies have found a widespread breed distribution, including mixed breed dogs.

The purpose of this study is to compare sedation effects of common preanesthetic drug combinations in dogs with and without the ABCB1-1Δ gene mutation to better inform veterinarians regarding dosing recommendations and potential side effects in affected dogs.

Eligibility: 

Dogs that are 1-8 years of age and are otherwise healthy are eligible to participate in this study. 

If you know your dog's MDR1 status (many breeders/owners of more at-risk breeds do), they may still be eligible to participate as long as they meet the above age and health requirements. We are particularly looking for Mutant/Mutant Collies at this time - additional compensation for participation in this clinical trial through the Collie Health Foundation may be available. 

If you agree to have your dog participate in this study, the participation will last for three hospital visits, the first visit will be short (< one hour), the subsequent two visits will last approximately 6 – 8 hours. All procedures on your dog will be performed by a licensed veterinarian with the assistance of either another licensed veterinarian, a veterinary technician, or a veterinary student all under the direct supervision of a board certified veterinary anesthesiologist. At the first visit, a cheek swab of the mouth will be taken to submit for genetic testing to see if your dog carries the gene mutation. The study will require 12 dogs in each genetic group (two normal copies of the gene (normal/normal), one normal copy of the gene and one mutation (normal/mutation) and two copies of the mutated gene (mutation/mutation). Once we have filled study subject spots for a group, additional dogs may not be used for the sedation part of the study. Genetic testing results will be provided to all owners of tested dogs, regardless of their further participation in the sedation part of the study.

If your dog qualifies for the study according to his/her genetic profile, at the second visit your dog will have a complete physical exam and blood will be drawn to check a packed red cell volume (PCV) and a blood chemistry to evaluate liver and kidney function to ensure your dog is healthy prior to sedation. Your dog will be administered 3 common preanesthetic drugs (maropitant, acepromazine and butorphanol). Your dog will be observed for up to 6 hours after sedation. We will be monitoring and documenting the level of sedation, heart rate, respiratory rate, blood pressure and body temperature. You will return at least 7 days later and your dog will receive the 3 drugs again but at a different dose and the same protocol will be followed. All drug doses are within recommended dose ranges for canine clinical patients.

Exclusion: 

Participation in this study is completely voluntary. You may choose not to have your animal participate. If you decide to have your animal participate, please realize that once drug administration has been performed this cannot be reversed. However, you may change your mind and withdraw your animal from further participation in the study at any time. If you decide not to have your animal participate in the study or if you withdraw your animal from the study early, it will not affect your right to receive treatment for your animal at the Iowa State University College of Veterinary Medicine. We can discuss the usual treatment options noted above and any alternative diagnostics, procedures, or treatments that may be available if your animal is not enrolled in the study.

Client Responsibilities: 

At this time, we ask that only clients that are willing to consider having their dog(s) participate in the sedation portion of this clinical trial participate in MDR1 testing their dog(s), so that we can appropriately allocate our resources. Based on your dog's genotype results (MDR1 status) and the requirements of our clinical trial at the time of receipt of your dog's results, your dog may or may not be asked to return for the sedation portion of our study. Results of your dog's MDR1 status will be provided regardless of if they are asked to return for the second part of the study.

Clients are strongly encouraged to schedule an appointment to collect their dog's samples for MDR1 testing ("cheek swabs") on-site (at the Lloyd Veterinary Medical Center in Ames, IA) with one of the study team members (please see the MDR1 flier and QR code, or email one of the team members listed). However, testing kits may be able to be sent to interested parties for at-home sample collection with return to ISU Lloyd Veterinary Medical Center for processing with prior approval.

Clients must be able to commute to the Lloyd Veterinary Medical Center in Ames, IA on two separate pre-scheduled days for the sedation portion of the clinical trial. On each of these days, owners must be able to drop off their pet in the morning and pick up their pet in the late afternoon/early evening. There will be a few dates offered to owners with dogs asked to return for the second part of this clinical trial, which will be filled on a first-come first-serve basis.

Client Benefits: 

You will not have costs from your animal’s participation in this study. You will be responsible for any costs associated with the normal course of treatment, the treatment of any complications that may arise, and unrelated medical conditions.

You will be compensated for your pet’s full participation in this study in the form of the results of the genetic testing ($70 value) and baseline bloodwork (~ $156 value). You will still receive genetic testing results if your dog cannot be used for the drug testing part of the study.

Contact: 

You are encouraged to ask questions at any time during this study.  For further information about the study, contact Dr. Bonnie L. Hay Kraus (bhkraus@iastate.edu) or Dr. Kristen Deom (kdeom@iastate.edu).