Electric blue eyes locked on the ball, the striking Husky sprints, then leaps and pounces, to catch the ball as it hits the pavement. Watching 11-year-old Bai Bai move with such agility and speed is surprising, as just a year ago she underwent surgery to repair a torn ligament.
Though a common procedure, this surgery was special because Bai Bai is participating in a Penn Vet clinical trial to investigate how dogs with varying degrees of knee joint arthritis recover after surgery to repair a ruptured cranial cruciate ligament (CCL).
Bai Bai, owned by third-year Penn Vet student Han (Michelle) Chia, just completed her one-year participation in the study, conducted by Dr. Kimberly Agnello, Assistant Professor of Small Animal Surgery at Ryan Hospital.
Bai Bai is one of seven dogs already participating in this study conducted through Penn Vet’s Veterinary Clinical Investigations Center (VCIC). Agnello expects to enroll dogs over the next two years.
Participation in the clinical trial – including the surgery, blood work, imaging, orthopedic examinations, activity monitoring, and gait analysis – is free. Support for this trial was generously provided by the John T. and Jane A. Wiederhold Foundation and by Penn Vet’s Companion Animal Research Fund.
CCL disease is a frequently encountered orthopedic condition in dogs, and is the most common reason for the development of arthritis in the knee, Agnello said. A variety of surgeries are available to treat a ruptured CCL, most with relative success, however some dogs don’t clinically do as well as others after surgery.
“We are looking at multiple variables in the knee at the time of surgery that could effect long-term knee function and prognosis,” Agnello said. “We are trying to identify which dogs will do better or worse after surgery.”
Because this is such a common disease, the trial’s main goal is to better understand the prognosis, which could eventually lead to better treatment, Agnello said. The treatment changes could be in surgery, pre- or post-operative management, or physiotherapy.
Before surgery, Agnello and her team conduct a full a physical examination on the dog, as well as digital radiographs (x-rays) and computed tomography (CT) scans of the good leg and the bad leg.
The pre-surgery analysis includes a subjective and an objective evaluation of the dog’s gait. The objective measures include various forms of kinetic gait analysis involving three different pieces of sophisticated electronic equipment, including force plate analysis, a pressure-sensitive walkway, and a pressure-sensitive treadmill.
Each patient in the study has the same type of surgery, a tibial plateau leveling osteotomy (TPLO), which is a common surgical stabilization procedure. The dogs each have the same repair, to make direct comparisons.
During surgery Agnello uses arthroscopy to conduct a comprehensive evaluation of the knee joint, based on her proposed canine arthroscopic grading system, including identification of the type of CCL injury, cartilage damage (arthritis), changes to the joint capsule, meniscal injury, and other ligament pathology.
“Another goal of this clinical trial is to evaluate the use of imaging modalities, such as radiography and CT scans, and compare the findings with arthroscopic visualization of pathology, and with the clinical outcome,” Agnello said.
After surgery, and for the entire year of their participation in the clinical trial, the dogs wear a collar to track their activity. Much like a Fitbit, the trackers measure movement and the intensity of movement, 24 hours a day. The data is captured and downloaded into a computer at each appointment.
The patients return for evaluation at two weeks, two months, three months, four months, six months, and a year. At each evaluation, the dogs go through the entire battery of tests for gait analysis. Digital radiographs are taken at each, and a CT scan at a year.
Student Michelle Chia is originally from Taiwan, but grew up in Baltimore, where she adopted her Husky, then two years old, from a shelter. The name Bai Bai means baby or precious one in Chinese.
The grey and white dog with the arresting blue eyes had been very healthy when she started limping a year ago. Chia took her to her primary vet, who prescribed rest and anti-inflammatory and pain medications. Bai Bai was even more lame a week later, so the veterinarian recommended a specialty service and surgery.
“Penn Vet was my first choice for the surgery,” Chia said. “I know Dr. Agnello and I trust her. She explained the clinical trial and it sounded interesting.
“I liked how Bai Bai would be regularly re-checked, and we would get more details on her recovery,” Chia continued. “The cost would be covered, and it was good to know that we could help the investigation and be part of the Penn Vet community.”
Chia watched the surgery, which she said was valuable since she wants to go into small animal medicine. “Michelle got to learn about doing clinical research, and see in more objective ways how well her dog was doing after surgery,” Agnello said.
The surgery went well. But the first few weeks afterwards were a bit challenging, as Chia followed the recommendation to restrict Bai Bai's exercise, which meant carrying the 50-pound dog up and down the stairs. Bai Bai had an unusual gait for about three months, but then started returning to normal. Today she is “back to being herself again,” Chia said.
“I believe I made the right choice,” Chia said. “She is happier, brighter. She loves to run, so it’s very important to her to have mobility in that leg.”
Agnello completed Bai Bai’s final evaluation in March for the year-long clinical trial. “I can’t detect that she is lame,” Agnello said. “She is running and playing.”
Agnello said Bai Bai does have arthritis in her joint. “At this point in time she is doing very well clinically. Her gait analysis is dramatically improved; she has full weight-bearing on her operated leg; she regained a significant amount of muscle mass; and she has pain-free, normal range of motion in her knee.”
How Bai Bai’s experience fits into the study is still not known.
“I can say clinically she did very well, but we are early in the study and I don’t have results yet to definitively say that the changes in her joint contributed to a better outcome,” Agnello said. “I do not have conclusions yet. We like to collect everything first, and then go back and look.”
Collecting and reporting the data is critical to the success of a clinical trial, Agnello said, and Penn Vet’s VCIC provides that expertise and support to researchers.
“The VCIC enables clinicians to focus on the medicine of the project,” said Michael DiGregorio, Managing Director of the VCIC, noting that 22 studies are currently ongoing. “There are a lot of ancillary procedures to make a clinical trial work. We can do everything surrounding the clinical study, except medical procedures.”
Some of those tasks are to devise a strategy for recruiting patients; screen and enroll patients; collect, manage, and analyze the data; develop protocols; submit regulatory submissions; negotiate and execute contracts; and assist with report writing.
In the case of Agnello’s study, the veterinary technicians are the main contacts for the owners, and they make appointments, arrange for the imaging, conduct the gait analysis, and manage the data.
The VCIC gait analysis equipment includes:
- Kistler Force Plate: Measures 30 different parameters, including peak vertical force and force exerted downward as the animal walks. It takes an expert to use it, as the dog has to walk between 1.6 and 1.9 meters per second and not accelerate or decelerate more than a half-meter per second.
- GAIT4Dog® Walkway: A rubberized mat with pressure sensors embedded throughout, it gives a measurement of vertical force, but also information about flexibility and other performance gaits, such as length of stride and hind leg reach.
- GAIT4Dog® DogTread Instrumented Treadmill: Allows similar kinetic data collection at a walk and a trot.
“One of interesting things about this CCL study is that we have the opportunity to use numerous modalities that measure clinical outcome and see how the data collected from these modalities compare with each other,” DiGregorio said.
For this CCL study, dogs must weigh 44 pounds or more, have a confirmed diagnosis of a unilateral CCL rupture, clinical signs of a CCL tear, no evidence of other concurrent orthopedic diseases, and ability to attend all seven required visits.
If you are interested in enrolling your dog in this study, or would like to learn more about this or other studies, please visit our website at www.vet.upenn.edu/vcic or contact the VCIC at 215-573-0302 or firstname.lastname@example.org.