At enrollment, an antibody titer, hematology and biochemistry panel will be used for screening purposes. Dogs will undergo a 3-minute electrocardiogram (ECG), a complete echocardiogram (ECHO) and the owners will complete a quality of life questionnaire. In order to participate in the study, dogs fulfilling the requirements will be randomly assigned to one of two groups: the placebo arm (cardiac injection with saline) or the gene therapy group (cardiac injection with the virus vector: AAV2/6-ARC-s100a1). Standard medical management for DCM and congestive heart failure will continue throughout the study in all dogs. Saline instead of empty virus will be used as the placebo so that control dogs can undergo gene delivery if the treatment group demonstrates a significant improvement compared to the placebo group. Owners will need to commit to re-evaluations at 2, 4, 6, 9, and 12 months at the University of Florida following therapy.
Dilated cardiomyopathy (DCM) is a very common form of heart disease in dogs. Only degenerative valve disease (also called mitral valve disease or endocardiosis or mitral insufficiency) and in some places heartworm disease are more common. It was not until the 1970s, when echocardiography began to be performed in veterinary institutions, that dilated cardiomyopathy could be diagnosed non-invasively with any certain degree of accuracy. The reported prevalence in dogs is approximately 0.5%.
Based upon a national database of dogs presented to veterinary schools in North America, we know that 5.8% of the Doberman Pinschers that were seen at a school had DCM, 5.6% of the Irish Wolfhounds presented had DCM. 3.9% of the Great Danes, 3.4 percent of the Boxers and 2.6% of the St. Bernards. In general, the dogs are middle age (4-10 years of age) with Males being over-represented (2:1). 70-80% of the Dobermans with congestive heart failure due to DCM are male and in a recent paper describing the disease in Dalmatians, all of the affected animals were male. This does not mean that female dogs are not affected by DCM, on the contrary, Dr. O’Grady at the University of Guelph found no sex predilection for Dobermans with subclinical (Asymptomatic or occult) DCM.
Familial and Genetic Influences
The general feeling is that most cases of DCM have a familial or genetic basis. This is based upon the observation of a higher prevalence in purebred dogs, in certain breeds and within certain families.
There are also strong indications in other breeds such as the Doberman, where DCM can affect more than 50 percent of family members. In Portuguese Water Dogs DCM appears to be autosomal recessive and in English Cocker Spaniels it is associated with a particular immune deficit. An autosomal dominant mode of transmission has been proposed for the Newfoundlands with DCM.
Taurine In the late 1980s taurine deficiency was recognized as the cause of dilated cardiomyopathy in the majority of cats with DCM. Since then investigators in the field have found a relationship between taurine deficiency and DCM in certain breeds such as Cocker Spaniels, Golden Retrievers and Newfoundlands.
Dogs with preclinical disease may go several years without clinical signs, so the diagnosis does not imply immediate risk of morbidity or mortality. Once the dogs become symptomatic, standard therapies for treatment of the heart failure and/or cardiac arrhythmias should be instituted. Nonetheless, the prognosis for Dobermans with DCM is poor.
Unless a reversible underlying cause is identified (e.g. taurine deficiency, primary tachyarrhythmia), the prognosis for DCM is often poor once overt clinical disease (CHF) develops, with most survival times being in months. The median survival time in a large retrospective study with mostly clinically significant dogs was 19 weeks, with one-year and two-year survival rates of 28% and 14%, respectively. In the Doberman, one-year survival rates of 10% or less have been reported, and treatment with triple therapy yielded a median survival time of 130 days.
Treatment of dilated cardiomyopathy is quite variable and depends upon the severity of the problem as well as the predominating symptom (e.g. fainting vs. coughing). The treatment may include things such as a moderately sodium restricted diet, diuretics, cardiac glycosides, nitrates, ACE inhibitors and various antiarrhythmic agents. Taurine and carnitine may also be added.
Meg Sleeper VMD graduated from the University of Pennsylvania veterinary school cum laude in 1993. Since completing her residency in 1997 and becoming board certified, she has worked in the section of cardiology at Penn with the exception of 1 year in private practice. She is an associate professor of cardiology and was section chief from 2001 through 2011. Primary research interests include inherited heart diseases, in particular inherited cardiomyopathies and therapeutic gene transfer.
Dr. Meg Sleeper has published numerous papers including over 70 peer reviewed original papers, over 50 review papers or case reports, and 4 books. In addition to lecturing at conferences including the American Heart Association, the American College of Veterinary Internal Medicine Forum, the Keystone Veterinary Conference, the World Feline conference and the American Veterinary Medical Association (AVMA), she has been the coordinator for the small animal cardiology section at the AVMA conference since 2009. In 2015 she joined the faculty at the University of Florida veterinary school.
Dr. Sleeper is on the editorial or review board of 11 journals and has served on the research (2008-2011) and examination (2005-2008) committees for the American College of Veterinary Internal Medicine (Cardiology). In early 2011, she was appointed to the Great Ape Heart Project. This project is focused on improving cardiac health in the 4 ape species (Chimpanzees, Gorillas, Bonobos and Orangutans).
Doctors and scientists take part in many kinds of research studies. Clinical research helps researchers understand how best to treat patients or helps them learn more about a particular condition or disease. There are many different forms of clinical research. One common form is a clinical trial. In a clinical trial, researchers test new drugs, medical devices or treatments.
Clinical trials may seek to discover new drugs, new ways of giving patients approved drugs, new combinations of approved drugs, new surgical techniques, devices, or biological products. Clinical trials are also conducted to test cutting-edge and novel therapies, like studies that involve gene therapy or gene transfer.
Informed consent is a process that helps you learn about the research study. After learning about the study, you will be able to ask the researcher or his/her staff questions. You should only agree to take part after you clearly understand the study and feel comfortable. You should take time to talk over your decision with your doctors, family, and friends. If you agree to take part, you will be asked to sign an "informed consent form."
You may consider having your pet participate in a study because:
You might consider not taking part in a study because:
There is no guarantee that a clinical trial will help your pet’s condition, but the results will contribute to knowledge that may make a difference in the future care of patients.
Clinical trials test new drugs, devices, or treatments. In some cases, taking part will not cost you anything. In other studies, the research team may bill you for drugs, devices, and services they provide. The study informed consent form will describe any costs to you in detail. If the information in the consent form is not clear, you should ask the research team to explain any costs before you sign the consent form.
Your pet is protected first and foremost by being told honestly and without bias what the known and potential risks are for participating in the trial. This information will be submitted to you in a language you will be able to understand. There is an Institutional Review Board (IRB) requirement that every participant in a clinical trial be informed about the possible risks, benefits and available alternatives. All of the information necessary to assist you in determining whether or not your pet should participate in a clinical trial is provided in a document called the "informed consent document." This document informs you of how to let the investigator know if you think your pet is experiencing a problem with the research and what resources are available to help you. You should ask any questions you may have about a clinical trial before signing the informed consent document. Even after you have signed the informed consent document to have your pet participate in a clinical trial, you should always speak to the investigator if you have questions or problems.
The Institutional Review Board (IRB) protects people and animals in research studies. The IRB includes scientists, non-scientists, and community members. The IRB reviews, approves, and monitors all in which pets take part. This oversight keeps risks to research participants as low as possible. The IRB also keeps track of ongoing studies to make sure they are being done in the right way.
This varies by study and will be covered in your Informed Consent Document.
Generally, participation ends when the study ends because it might not be safe or effective to continue treatment based on what is known at the time. Sometimes patients can remain on the study drug if they are responding to the new treatment; however, this is the exception rather than the rule.