Clinical Investigation Center

Completed clinical studies

This section highlights our completed clinical trials and studies, with publication information if applicable. Publication links will take you to PubMed.

Anesthesia and Pain Management

Anesthesia and Pain Management

Using amantadine as a pain-reliever in osteoarthritic cats

October 2020

Owner evaluation of quality of life and mobility in osteoarthritic cats treated with amantadine or placebo
The goal of this placebo-controlled study was to determine if amantadine given to client-owned cats with verified osteoarthritis led to an observed improvement in quality of life and mobility, as perceived by the owner. Thirteen healthy client-owned cats with clinical and radiographic evidence of osteoarthritis and owner-identified mobility impairment were studied. 

Study outcomes
  • Amantadine significantly decreased activity, but a significantly greater proportion of owners reported improvement in quality of life with amantadine compared with placebo
  • Amantadine appears to be an option for the symptomatic treatment of osteoarthritis in cats.

Cardiology

Cardiology

Using a low profile Amplatz Canine Duct Occluder prototype in small dogs

September 2015

Patent ductus arteriosus occlusion in small dogs utilizing a low profile Amplatz Canine Duct Occluder prototype
The goal of this study was to develop procedures and assess the safety, utility, and effectiveness of a low profile Amplatz Canine Duct Occluder (ACDO) prototype for dogs considered too small for currently available canine duct occluders. Twenty-one dogs with left-to-right shunting patent ductus arteriosus (PDA) were studied. PMID: 26363940

Study outcomes
  • All twenty-one dogs received successful ductal occlusion with no complications during the procedure, and without the device lodging inappropriately
  • Of the 17 dogs that returned for long term follow up, all had complete ductal occlusion
  • The low profile ACDO is a safe and effective method of PDA occlusion in the small dog

Designing, developing, and delivering the the Amplatz Canine Duct Occluder for use in dogs

January–February 2008

Minimally invasive per-catheter patent ductus arteriosus occlusion in dogs using a prototype duct occluder
This research involved the design and development of a novel device to improve outcomes for dogs with complications related to cardiac devices. The Amplatz Canine Duct Occluder (ACDO) was designed to conform to the morphology of patent ductus arteriosus in dogs and a minimally invasive per-catheter procedure for device delivery in this species. Eighteen client-owned dogs of various breeds with per-catheter patent ductus arteriosus. PMID: 18289299

Study outcomes
  • Achieved successful placement of the ACDO in all 18 dogs
  • Confirmed complete occlusion in 17 of the 18 dogs during the procedure, at 1 day afterward, and at 3 months post-procedure
  • Twelve of the 13 dogs had complete occlusion 12 months or more post-procedure<--break->

Dermatology

Dermatology

Understanding the bacterial community on the skin of healthy domestic dogs

March 2017

Diverse bacterial communities exist on canine skin and are impacted by cohabitation and time
The primary aims for this study were to evaluate whether or not there is a core bacterial community living on the skin of healthy domestic dogs from Minnesota and if body site, dog cohabitation, and seasonality have an impact on this community. This study sampled the skin bacterial communities of 40 dogs belonging to 20 households across three seasons (spring, summer, and winter).  PMID: 28289569

Study outcomes
  • The canine skin bacterial community is highly diverse and highly variable
  • Researchers did not see significant differences in overall bacterial community structure between the three skin sites
  • Scientists observed significant differences when the samples were grouped by time point
  • Dogs living together have significantly more similar bacterial communities on their skin than dogs not living together

Investigating how well lokivetmab reduces itching in dogs with atopic dermatitis

September 2016

A blinded, randomized, placebo-controlled, dose determination trial of lokivetmab (ZTS-00103289), a caninized, anti-canine IL-31 monoclonal antibody in client owned dogs with atopic dermatitis
The goal of this study was to compare three doses and describe the dose response of lokivetmab in dogs with atopic dermatitis. Owners assessed dogs for itching and the clinicians used the Canine AD Extent and Severity Index (CADESI-03) tool. Clinicians at 14 veterinary clinics enrolled client owned dogs with chronic AD. PMID: 27647513

Study outcomes
  • Lokivetmab at 0.5 and 2.0 mg/kg reduced itching compared to placebo for at least one month
  • Among a diverse population of 162 client owned dogs with a clinical diagnosis of AD, treatment with two monthly doses of lokivetmab was safe, based on observations made over a 42-day period
  • Further studies were needed to better understand variability among dogs in a broader population of dogs with AD

Assessing the long‐term safety, efficacy, and quality of life of oclacitinib‐treated dogs

June 2015

Long-term compassionate use of oclacitinib in dogs with atopic and allergic skin disease: safety, efficacy and quality of life
This study assessed long-term safety, efficacy and quality of life of oclacitinib-treated dogs enrolled in a compassionate use protocol. Dogs had previously received oclacitinib in a clinical trial. Two hundred and forty-seven client-owned dogs with allergic skin disease that had previously benefited from oclacitinib therapy were enrolled. PMID: 25688708

Study outcomes
  • Dogs showed more than 50 percent reduction in itching in 64 percent of cases, and same reduction in dermatitis in 66 percent of cases
  • Owners saw a positive quality of life in more than 90 percent of dogs
  • Oclacitinib was safe and efficacious for long-term use and improved the quality of life for dogs in this study

Using oclacitinib to treat atopic dermatitis in dogs

December 2013

A blinded, randomized, placebo-controlled trial of the efficacy and safety of the Janus kinase inhibitor oclacitinib (Apoquel) in client-owned dogs with atopic dermatitis
This multi-site study looked at efficacy and safety of oclacitnib (Apoquel) for the control of atopic dermatitis in a randomized, double-blind, placebo-controlled trial. Clinicians at 18 specialty clinics enrolled 299 client-owned dogs with a history of chronic AD. PMID: 24581322

Study outcomes
  • Dogs had a reduction from baseline in owner-assessed itching scores and dermatologist CADESI-02 scores 
  • Significant differences seen at all study time points (days 1, 2, 7, 14, and 28)
  • Apoquel is now available as a prescription medication for dogs

Large Animal Medicine and Surgery

Large Animal Medicine and Surgery

The efficacy of imiquimod 5% cream (Aldara®) in the treatment of aural plaque in horses: a pilot open label-clinical trial

The purpose of this study was to investigate the efficacy of imiquimod 5% cream in the treatment of equine aural plaques. PMID: 20500494

Study Outcomes
  • Complete resolution of lesions was noted in all horses immediately post-treatment and long-term resolution was 88%
  • All horses were followed for 12-22 months and only two horses had a recurrence of lesions in that time
  • Topical application of imiquimod 5% cream is an efficacious treatment for aural plaque in horses

Efficacy of imiquimod 5% cream in the treatment of equine sarcoids: a pilot study 

The purpose of this study was to evaluate imiquimod 5% cream, an immune response modifier with potent antiviral and antitumor activity, as a topical treatment of equine sarcoids. PMID: 16827669

Study Outcomes
  • Results showed 12/15 lesions reduced in size by >75%, and 9 resolved completely
  • Results suggest that topical imiquimod is a therapeutic option for the treatment of equine sarcoids

Instructional links

Aldara Frequently asked questions for Owners
Veterinarian Instructions for use of Aldara®(imiquimod)

Neurology

Neurology

Understanding intravenous topiramate in dogs with epilepsy

December 2016

Intravenous topiramate: Pharmacokinetics in dogs with naturally occurring epilepsy
The goals of this study were to characterize the pharmacokinetics of intravenous dose of topiramate in dogs with naturally occurring epilepsy to advance both animal and human outcomes. Five dogs with naturally occurring epilepsy were studied. Three were getting at least one antiseizure drug as maintenance therapy. PMID: 27995128

Study outcomes
  • IV topiramate has a relatively rapid onset of action
  • Dogs on phenobarbital maintenance therapy required a higher dose to reach target concentration
  • Topiramate is a good candidate for further evaluation for seizure emergencies in dogs and people

Using fosphenytoin to treat canine status epilepticus

June 2015

Canine status epilepticus treated with fosphenytoin: A proof of principle study
Epilepsy and canine status epilepticus occur naturally in dogs with similar prevalence, presentation and percentage of refractory cases as human epilepsy. The goal of this study was to assess 31 dogs to determine if canine status epilepticus treated with fosphenytoin (FOS) results in a similar responder rate as for people. PMID: 25953073

Study outcomes
  • FOS is tolerated and effective in canine status epilepticus at plasma phenytoin levels which are clinically relevant for human status epilepticus
  • Naturally occurring canine status epilepticus can be used as a translational platform for future studies of novel compounds for status epilepticus

Oncology

Oncology

Treating feline oral squamous cell carcinoma with anti-tumor gene therapy

June 2017

Therapeutic targeting of protein kinase CK2 gene expression in feline oral squamous cell carcinoma: A naturally occurring large-animal model of head and neck cancer
The goal of this clinical trial was to identify a safe dose and to determine the efficacy of anti-tumor gene therapy delivered using targeted nanocapsules for cats with tumors of the oral cavity. Nine cats were involved in this study. PMID: 28335614

Study outcomes
  • The therapy was generally well tolerated
  • The therapy showed preliminary antitumor activity in cats with tumors of the oral cavity

Using a new drug to target sarcomas

May 2017

Safe and effective sarcoma therapy through bispecific targeting of EGFR and uPAR
The goals of these clinical trials were to identify a biologically active dose of a bispecific ligand targeted toxin (eBAT) and to determine its potential efficacy in 23 dogs with hemangiosarcoma of the spleen. PMID: 28193671

Study outcomes
  • eBAT improved 6-month survival from under 40 percent in a comparison population to approximately 70 percent in dogs treated at a biologically active dose 
  • Six dogs were long-term survivors, living more than 450 days
  • eBAT abated expected toxicity associated with EGFR targeting, a finding supported by mouse studies
  • eBAT has potential for use in the treatment of human cancer patients (MCT). 
  • eBAT did not have any of the side effects that are associated with other therapies that attack the same targets
  • Addition of eBAT to the standard of care improved overall survival and increased the proportion of long term survivors

Immunotherapy for canine cancer

December 2016

Eradication of canine diffuse large B-cell lymphoma in a murine xenograft model with CD47 blockade and anti-CD20
The goal of this basic research study was to initiate development of immunotherapy approaches for dog cancer. PMID: 27856424

Study outcomes
  • The combination of two immunological treatments appeared safe in laboratory models of canine lymphoma
  • This combination showed extremely promising results in pre-clinical laboratory studies 

Evaluating the safety of Salmonella enterica serovar Typhimurium for canine osteosarcoma

February 2021

Salmonella-IL2 has been licensed to Salspera LLC and is now called Saltikva. (Salspera.com) There is an ongoing Phase II trial for human patients with metastatic stage IV pancreatic cancer occurring at the Segal Cancer Center in Montreal.  On the Veterinary side, Salmonella-IL2 has been licensed to a veterinary pharmaceutical company and is going through the regulatory steps at the USDA and will be used for dogs with sarc.

June 2016

A phase I clinical study to evaluate safety of orally administered, genetically engineered Salmonella enterica serovar Typhimurium for canine osteosarcoma
The goals of this clinical trial were to identify a safe dose of oral recombinant Salmonella-IL2 and to determine its efficacy in 19 dogs with bone cancer treated with the standard of care. doi/10.1002/vms3.32

Study outcomes
  • Oral Salmonella IL-2 was safe 
  • Patients that received Salmonella IL-2 developed transient elevations in white blood cell counts
  • Salmonella IL-2 was associated with longer remissions than what was expected with standard of care alone
  • About ~20% of the treated dogs survived more than 700 days

Long-term oral therapy for osteosarcoma in dogs

April 2015

Impact of toceranib/piroxicam/cyclophosphamide maintenance therapy on outcome of dogs with appendicular osteosarcoma following amputation and carboplatin chemotherapy: a multi-institutional study
The goal of this multi-institutional clinical trial was to determine if a new multidrug combination would improve survival outcomes for 126 dogs with bone cancer. PMID: 25923466

Study outcomes
  • Dogs that received additional drug therapy had more side effects than dogs that received only the standard of care
  • The addition of Palladia to treat dogs with bone cancer did not lead to meaningful improvements in survival

Comparing the immune responses of dogs to humans and mice

April 2015

Stimulation with concanavalin-A induces IL-17 production by canine peripheral T cells
The goal of this basic research study was to determine if the basic mechanisms of immune responses in six dogs resemble those of humans and mice. DOI: 10.3390/vetsci2020043

Study outcomes
  • The mechanisms that control generation of inflammatory (T helper type-17) and immunosuppressive (T regulatory) responses in dogs were very similar to those that control comparable human and mouse immune responses 

Targeted inhibitors of aurora kinases

March 2015

Canine osteosarcoma cells exhibit resistance to aurora kinase inhibitors
The goal of this basic research study was to determine if inhibitors of proteins that control cell division, called aurora kinases, might be highly effective to treat bone cancer. PMID: 23410058

Study outcomes
  • Canine bone cancer cells appeared very resistant to aurora kinase inhibitors
  • These compounds are unlikely to be useful as single agents to treat bone cancer

Adding Valspodar to chemotherapy when treating dogs with lymphoma

February 2015

A double blinded, placebo-controlled pilot study to examine reduction of CD34 +/CD117 +/CD133 + lymphoma progenitor cells and duration of remission induced by neoadjuvant valspodar in dogs with large B-cell lymphoma
The goal of this clinical trial was to determine if addition of Valspodar to chemotherapy would lead to sensitization of the cells that are responsible for causing lymphoma in 20 dogs. PMID: 28357033

Study outcomes
  • Valspodar was well tolerated
  • Survival time for dogs with diffuse large B cell lymphoma treated with doxorubicin as single agent exceeded historical expectations
  • Valspodar did not appear to sensitize tumor propagating cells to chemotherapy

Testing to Tailor Tumor Treatment

March 2014

Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed) trials
The primary goal of this multicenter clinical trial was to determine if personalized medicine was feasible in 31 dogs with cancer. In personalized medicine, a variety of tests are performed to identify the specific molecular abnormalities in an individual’s tumor. Knowledge of these abnormalities allows treatment to be tailored to that specific individual. PMID: 24637659

Study outcomes
  • A consortium of veterinary clinics and laboratories across the country produced personalized medicine reports in less than one week
  • Reports match the specific molecular abnormalities in a tumor to potential therapeutic options
  • In this study, dogs with the same cancer type had different molecular abnormalities, suggesting the need for tailored treatments

Treating canine lymphoma with Verdinexor

February 2014

Preclinical evaluation of the novel, orally bioavailable Selective Inhibitor of Nuclear Export (SINE) KPT-335 in spontaneous canine cancer: results of a phase I study
The goals of this clinical trial was to identify a safe dose of Verdinexor (KPT-335) and to determine its efficacy in 17 dogs with lymphoma. PMID: 24503695

Study outcomes
  • Verdinexor was safe 
  • Verdinexor was given Minor Use/Minor Species approval following the study

Characterization of canine natural killer cells

September 2013

Isolation and characterization of canine natural killer cells
The immunophenotype and function of natural killer (NK) cells in humans and mice are well defined, but canine NK cells were previously incompletely characterized. The goal of this basic research study was to develop methods to isolate and characterize canine natural killer cells. PMID: 23876304

Study outcomes
  • Developed methods to efficiently isolate canine natural killer cells
  • Showed that the biological traits of these cells in dogs are similar to those of humans and mice 

Improving the survival of dogs with spontaneous bone cancer with fas ligand gene therapy 

December 2012

Inflammation, apoptosis, and necrosis induced by neoadjuvant fas ligand gene therapy improves survival of dogs with spontaneous bone cancer
The goals of this clinical trial were to identify a safe dose of adenovirus-Fas ligand (Fasaret) administered into the tumor and to determine its efficacy in 56 dogs with bone cancer treated with the standard of care. PMID: 22850679 

Study outcomes
  • The therapy was safe
  • Patients with Fasaret induced inflammation in the tumor had improved outcomes
  • Dogs treated with Fasaret whose tumors had lower expression of Fas protein had longer survival
  • 40 percent of dogs that developed strong tumor inflammation survived more than 1,200 days

A new chemotherapy agent for dogs with lymphoma

May–June 2012

Phase I study to determine the maximal tolerated dose and dose-limiting toxicities of orally administered idarubicin in dogs with lymphoma
The goal of this clinical trial was to identify a safe dose of a new chemotherapy agent for 31 dogs with lymphoma. PMID: 22404399

Study outcomes
  • The therapy was generally well tolerated
  • The therapy showed preliminary antitumor activity in dogs with lymphoma

Immunotherapy for lymphoma in dogs using artificial immune cells

June 2011

Immunotherapy with autologous tumour antigen-coated microbeads (large multivalent immunogen), IL-2 and GM-CSF in dogs with spontaneous B-cell lymphoma
The goals of this clinical trial were to determine the safety, efficacy, and immune response associated with a new immunotherapy treatment in 15 dogs with lymphoma after standard chemotherapy. PMID:21569195

Study outcomes
  • The treatment was safe
  • Half of treated dogs developed a positive immune response upon receiving the therapy

Genetics of cancer in companion animals

The goals of these basic research studies are to understand what causes cancer and what drives its behaviors.

Study outcomes

Small Animal Medicine

Small Animal Medicine

Understanding breed-specific urinary metabolites and their relationship with stone status 

January 2015

Fasting urinary calcium-to-creatinine and oxalate-to-creatinine ratios in dogs with calcium oxalate urolithiasis and breed-matched controls
Hypercalciuria and hyperoxaluria are risk factors for bladder or kidney stones. This study compared urinary metabolites (calcium and oxalate) and blood ionized calcium (iCa) concentrations between CaOx stone formers and breed-matched stone-free controls for 47 Miniature Schnauzers, 27 Bichons Frise, and 15 Shih Tzus. doi:10.1111/jvim.12527

Study outcomes
  • Hypercalciuria is associated with CaOx stone status in these breeds 
  • Oxalate‐to‐creatinine ratio did not correlate

Diagnosing clinical acute pancreatitis in dogs

August 2012

A multi-institutional study evaluating the diagnostic utility of the spec cPLTM and SNAP®CPLTM in clinical acute pancreatitis in 84 dogs.
This multi-site study examined the diagnostic usefulness (sensitivity and specificity) of the pancreatic lipase blood test. doi:10.1111/j.1939-1676.2012.00951.x 

Study outcomes
  • These tests have a higher sensitivity than serum amylase or lipase activity in diagnosing clinical acute pancreatitis in dogs.

Treating immune-mediated hemolytic anemia in dogs

April 2010

Treatment of immune-mediated hemolytic anemia with individually adjusted heparin dosing in dogs
A prospective clinical trial comparing the treatment of 15 dogs with immune-mediated hemolytic anemia with individually adjusted doses of heparin to standard of care, fixed low heparin dosing. doi:10.1111/j.1939-1676.2010.0505.x

Study outcomes
  • A greater survival rate in the adjusted heparin dosing group than in the group with standard care

Small Animal Surgery

Small Animal Surgery

Treating medial patellar luxation in dogs

January 2020

Comparison of Semi-Cylindrical Recession Trochleoplasty and Trochlear Block Recession for the Treatment of Canine Medial Patellar Luxation: A Pilot Study
The goal of this study was to compare an alternative method for trochleoplasty, semi-cylindrical recession trochleoplasty (SCRT), to trochlear block recession (TBR) by assessing recessed trochlear depth, patellar depth, patellar articular contact with the trochlea, recessed trochlear surface area, procedure time, complications and functional outcome. PMID: 33242894

Study outcomes
  • There was no significant difference in the measured variables between SCRT and TBR 
  • At 8-weeks post-surgery, no patella had re-luxated.
  • SCRT was subjectively easier to perform, especially in smaller dogs, therefore is an acceptable method of trochleoplasty

Evaluating synovial fluid biomarkers in dogs with and without lameness from spontaneous osteoarthritis

July 2019

Correlation between synovial fluid cytokine concentrations and limb function in normal dogs and in dogs with lameness from spontaneous osteoarthritis
The goal of this study was to determine the relationship between synovial fluid biomarker concentrations and severity of lameness and to determine if synovial fluid biomarker concentrations could differentiate normal from osteoarthritic joints. PMID: 31032990

Study outcomes
  • There were differences in pro-inflammatory and anti-inflammatory biomarkers found between osteoarthritis (OA) and normal joints.
  • No relationship was found between biomarker concentrations and gait asymmetry in dogs with OA.
  • Future studies are needed to assess the effect of disease chronicity, specific joints and potential new biomarkers

Treating osteoarthritis in dogs with an oral nutraceutical

September 2017

Efficacy of an oral nutraceutical for the treatment of canine osteoarthritis: A double-blind, randomized, placebo-controlled prospective clinical trial
The goal of this study was to assess the safety and efficacy of an oral nutraceutical (Glu/CS+) for the treatment of clinical osteoarthritis (OA) in dogs. Groups were compared using activity monitors and an owner assessment of pain in their dog (Canine Brief Pain Inventory). PMID: 28763523

Study outcomes
  • There were no serious adverse events
  • There was no difference found between groups in activity counts 
  • Owner assessment of pain improved for both groups but there was no difference found between groups. This suggests a caregiver placebo effect.

Treating spontaneous cranial cruciate ligament rupture in dogs

July 2017

Long-term outcome of an intra-articular allograft technique for treatment of spontaneous cranial cruciate ligament rupture in the dog
The goal of this study was to determine the 12-month outcome in 10 dogs with spontaneous cranial cruciate ligament (CCL) rupture with an intra-articular decellularized allograft. Dogs were evaluated with an owner questionnaire, radiographs, and force platform gait analysis before and two, six, and 12 months after surgery. PMID: 28370152

Study outcomes
  • Intra-articular repair using a decellularized allograft can provide functional clinical outcomes in dogs with CCL disease as evidenced by owners reporting improvement in level of pain and mobility especially over the first six months and peak vertical force and vertical impulse improved across all time points
  • Ground reaction force asymmetry index for peak vertical force and vertical impulse results varied
  • Osteoarthritis scoring did not change over the 12-month period and some femoral-tibial translation was detected on standing horizontal beam radiographs
  • A better understanding of long-term engraftment after this procedure is needed

Treating overweight dogs with cranial cruciate ligament rupture

May 2015

Short-term and long-term outcomes for overweight dogs with cranial cruciate ligament rupture treated surgically or nonsurgically
The goal of this study was to determine short- and long-term rates of successful outcomes of surgical and nonsurgical treatments for 40 overweight dogs with cranial cruciate ligament rupture (CCLR). A successful outcome was defined as an affected limb net ground reaction force > 85% of the value for healthy dogs and a ≥ 10% improvement in values of questionnaire variables. PMID: 23634680

Study Outcomes
  • Overweight dogs with CCLR treated via surgical and nonsurgical methods had better outcomes than dogs treated via nonsurgical methods alone
  • Surgical treatment group dogs had a higher probability of a successful outcome vs nonsurgical treatment group dogs
  • Almost two-thirds of the dogs in the nonsurgical treatment group had a successful outcome at one year

Managing pain in dogs after orthopedic surgical procedures

July 2013

Comparison of the analgesic efficacy of perioperative firocoxib and tramadol administration in dogs undergoing tibial plateau leveling osteotomy
The goal of this study was to compare the analgesic efficacy of perioperative firocoxib and tramadol administration in 30 dogs undergoing tibial plateau leveling osteotomy (TPLO). Firocoxib and tramadol were examined alone and in combination. PMID: 23822079

Study outcomes
  • Dogs that received firocoxib orally, alone or in combination with tramadol, had lower pain scores, lower rescue opiate administration, and greater limb function than dogs that received only tramadol
  • When used alone, oral administration of tramadol may not provide sufficient analgesic efficacy to treat dogs with pain after orthopedic surgical procedures