For Kids, Clinical Trials Give Renewed Hope

At first glance, Holden Trent looks like the typical all-American boy – soccer jersey, blonde hair and blue eyes, even freckles. But unlike most kids, he spent much of his childhood sidelined by painful tummy aches and frequent trips to the bathroom. Holden has Crohn’s disease, a chronic inflammatory illness affecting the gastrointestinal tract, for which there currently is no cure. Only after enrolling in a clinical trial of a new therapy for Crohn’s has Holden begun to feel like a kid again, chatting with friends at school and running around the soccer field.

Sandy Kim, Holden’s physician, says success stories like his are the reason she decided to offer clinical trials to her patients. Kim, an assistant professor of pediatrics in the division of gastroenterology at UNC-Chapel Hill, has long advocated for ways to improve the care of children with inflammatory bowel diseases, or IBD. A pure clinician at heart, she has come to believe that appropriate clinical trials and extensive research is the only way that physicians will know how best to treat kids.

“It wasn’t that long ago when we didn’t have a lot of medications tested in children; we had to extrapolate from adult studies. It is important that we be able to study these medications in kids, because kids are not small adults,” said Kim. “There are a lot of things that are different – for one thing, kids with chronic illness are diagnosed earlier in life and often have more severe disease. Plus, we have to examine the side effects of medications more seriously in kids, whose immune systems and bodies are still developing.”

During her clinical pediatric gastroenterology fellowship at Texas Children’s Hospital, Kim helped start a camp for kids with chronic disease and illnesses, particularly IBD and liver disease. It was there that she began to feel an obligation to make the lives of the campers better, ultimately questioning her plans to go into private practice. So when Balfour Sartor, M.D., director of the UNC Multidisciplinary IBD Center, asked her to take a step back and spend a few years as a research postdoctoral associate in his lab, she decided to give research a try.

Ten years later, Kim serves as chair for the Crohn’s and Colitis Foundation of America’s (CCFA) Pediatric Affairs Committee. She currently co-leads teams focused on improving care for pediatric patients with inflammatory bowel disease as part of the Chronic Care Collaborative at North Carolina Children’s Hospital and the national ImproveCareNow pediatric IBD quality improvement network. Her ongoing NIH- and CCFA-funded research focuses on the role of bacterial triggers of inflammation in IBD.

“Through research, I can ask the questions that bother me as a clinician and study them, whether by isolating bacteria, sequencing genes, working in mouse models, testing in patients, or taking things further down the line and looking at it from a quality improvement standpoint,” said Kim. “Learning how to think in a hypothesis-driven manner has made me a better and wiser physician, causing me to question and think outside the box when I feel things can be done better.”

Scientific studies that question and improve upon the standard of care have helped many children with IBD, including Holden. For the last few years Holden has been part of a trial for a medication called adalimumab (trade name HUMIRA®), which has already been approved for adults with Crohn’s disease. Adalimumab works by blocking a chemical produced by immune cells, called tumor necrosis factor, that perpetuates inflammation in different types of inflammatory disorders like Crohn’s disease and ulcerative colitis.

In the first phase, Kim and her colleagues involved in this multiple site clinical trial tested whether adalimumab would reduce the inflammation and induce remission in Crohn’s disease. Patients like Holden who experienced remission in the trial have been kept on the medication through a maintenance phase, with the clinicians keeping an eye out for any unexpected side effects.

“If I enroll patients in a trial, it is because that is the medication I would have used anyway. That is one thing I feel very strongly about,” said Kim. “I feel that these medications are effective because they have already been approved in adults; the reason we are doing these trials is to study their safety and effectiveness in kids.”

For kids dealing with Crohn’s disease, even incremental improvements in treatment could help them spend less time worrying about living with a chronic illness and more time just being a kid.

“I made a promise back in 1999 at that camp in the outskirts of Houston that I will never break,” said Kim. “It was during a wish boat ceremony, where each child had a chance to say their wishes. I still remember one of the kids lighting his candle saying I want people like Dr. Sandy and the people she works with to not only take care of us, but to find a cure. This still gets to me. With a request like that, how could I not try?”