Let’s Get Clinical

Researchers across Carolina manage clinical trials to get novel treatments and interventions into the hands of those who need them most.

Clockwise from top-left: Edwin Kim, William Miller and Vivian Go, Shawn Kneipp, Laura Jacox and Sugar, and Andrew Satterlee, Shawn Hingtgen and David Kram
Clockwise from top-left: Edwin Kim, William Miller and Vivian Go, Shawn Kneipp, Laura Jacox and Sugar, and Andrew Satterlee, Shawn Hingtgen and David Kram (composite by Alyssa LaFaro)
May 20th, 2024

All five of Carolina’s health schools — the School of Medicine, Eshelman School of Pharmacy, Adams School of Dentistry, Gillings School of Global Public Heath, and School of Nursing — are engaged in clinical trials. And, in honor of Clinical Trials Day, we’re highlighting researchers from each one to unpack the trials they’re currently working on.

Clinical context

Before the 1950s, pediatric acute lymphoblastic leukemia (ALL) — a type of cancer where the bone marrow makes too many immature white blood cells — was universally fatal. Then, a clinical trial run by the National Cancer Institute produced durable remission rates in about a third of the children enrolled.

“This was an unprecedented leap,” says David Kram, a UNC-Chapel Hill pediatric neuro-oncologist. “From there, clinical trials were developed by cooperative groups all over the world and in close collaboration — and some competition — with each other.”

Today, the cure rate for ALL is over 90%. More than 85% of children with the disease are now enrolled in clinical trials across North America and Europe.

This story is not unique to ALL.

In the early 1980s, the average life expectancy for someone living with AIDS was three years after diagnosis. By 2000, researchers from the National Institutes of Health (NIH) had developed an antiretroviral therapy to prevent people with HIV from developing AIDS and created better testing and interventions to curb the number of children born with the disease.

Thanks to clinical trials, people with the disease can now live a relatively normal life. Same goes for those with hemophilia, hepatitis, and various cancers.

“Clinical trials are at the heart of all medical advances,” Kram stresses. “They are the major tool used to explore whether new tests or treatments for a disease work and are safe.”

Phases of progress

Clinical trials involve human participants who take a drug or engage in an intervention to help researchers uncover the success of those treatments.

“People often think about clinical trials when new drugs, surgical treatments, or vaccines are being developed and tested, but many clinical trials are done to evaluate whether social, educational, or behavioral interventions improve health,” says Shawn Kneipp, a professor in the UNC School of Nursing.

People participate in clinical trials for many reasons. They gain access to new therapies otherwise inaccessible — and, oftentimes, this might be their “last option” for improving their disease. Others enroll to receive additional care and attention from clinical trial staff. And some just hope to move science forward.

That’s what research is: incremental steps forward over time. And all research begins with discovery. A question leads to an experimental setup that creates data for the researcher to analyze. Then it moves into the preclinical stage. For a drug, this involves small-scale lab testing to prove effectiveness. Promising treatments move into clinical trials.

The largest public funder of clinical trials in the U.S. is the NIH, which uses four phases to propel a drug forward. Each one incrementally includes more participants as researchers continue to prove a drug’s safety and document its side effects. In Phase IV, after reviewing the clinical trial data, the Federal Drug Administration (FDA) can approve the drug and make it available to the general population.

Carolina researchers are involved in various phases of clinical trials. Here’s a look at multiple projects, the researchers behind them, and the health needs they are striving to meet.

Developing personalized treatments for brain cancer

Andrew Satterlee, Shawn Hingtgen, and David Kram in the lab

Andrew Satterlee, Shawn Hingtgen, and David Kram (photo by Alyssa LaFaro)

UNC Eshelman School of Pharmacy researchers Andrew Satterlee and Shawn Hingtgen and UNC School of Medicine researcher David Kram are running a clinical trial that tests patients’ tumors to develop better, more personalized treatments for cancer in the future.

What is your research focus?

As oncology researchers and clinicians, we focus on treating cancer. We know that nine out of 10 new cancer drugs that make it to the clinical trial phase fail to benefit patients, and thus fail to gain FDA approval for further use. This is an enormous challenge and why there are still so many incurable cancers.

There are many reasons why drugs fail in the clinical trial phase after succeeding so brilliantly in the preclinical testing phase. We believe a key barrier is in the models themselves: When a new cancer drug works in preclinical disease models but fails to work in humans, something must be wrong with the model. Our research focuses on inventing a new and better cancer model.

Tell us about the clinical trial you’re running.

We have developed a model that can test broad types of brain cancer better than any model currently used. For example, instead of using cancer cells that have been grown in plastic dishes, our model uses a patient’s own tumor tissue, right after it is removed from the patient’s brain. It’s tough to keep tumors alive after they are taken out of a person’s body, but our model is very good at maintaining and testing the tumor tissue, no matter the tumor type.

To prove that our brain tumor model effectively replicates a patient’s tumor, we need to test as many patient-specific tumor samples as possible and compare the behavior and drug responses in the real tumors and in our models. This is precisely what our clinical trial aims to do.

This trial is open at UNC for children and adults with primary central nervous system tumors. After undergoing surgery, their tumor tissue is used for clinical testing. We take what’s left to establish a patient-specific brain tumor model in our lab.

We then “treat” the model with various drugs and compare the results to the drugs that have been prescribed to patients by their doctors. We don’t inform a patient’s treatment plan or use this data to help guide clinical decision-making. That type of intervention will only occur after we see enough positive associations between our model’s results and what happens to patients after their doctor-prescribed treatments.

Have you made any discoveries thus far?

The trial opened in August 2023. It’s still early, but we are learning that our processes are working. Every one of the brain tumor tissue samples we’ve received from enrolled patients has been successfully tested and analyzed.

This has been no easy feat. The level of coordination that is required between the operating room staff, the neurosurgeons, the neuro-oncologists, and our lab personnel is enormous — and we’re achieving it cohesively and consistently. That speaks volumes about the strong collaborative environment here, which allows us to conduct true translational research.

What are your hopes for the future of this trial?

There are too many children and adults suffering and dying from cancer. If our model better recapitulates the real thing, then the field will be in a stronger position to select the best preclinical new drugs to bring to the clinical trial phase. One day, we may even use this approach to help guide treatment decisions in the clinic. We hope that our current clinical trial helps us take a big step forward in proving our model’s validity.

Making dentistry less stressful and more fun for kids

Laura Jacox sits next to Sugar, the therapy dog, in a dentist-like room

Laura Jacox and Sugar (photo by Alyssa LaFaro)

UNC Adams School of Dentistry researcher Laura Jacox is running a clinical trial to measure the impact of animal-assisted therapy on anxiety and pain in pediatric dental patients.

What is your research focus?

By training, I am a craniofacial developmental biologist, meaning I study the development of the mouth and face. Clinically, I am a licensed dentist and boarded orthodontist who strives to improve the position, function, and esthetics of the teeth and jaws in growing patients and adults. Drawing on both backgrounds, I am a clinician-scientist, where I work to answer questions to improve clinical care for dental patients.

One of my projects evaluates whether animal therapy with dogs can be used to improve children’s experiences at the dentist — to help manage fear, anxiety, and pain without medications. Studies have found that kids and adults with high dental anxiety avoid going to the dentist, and as a result, have worse oral health.

When these anxious patients decide to see the dentist, their needs are greater and more emergent — and often require surgery and/or dental extractions. For children with high dental anxiety, they often need medication or more significant anesthesia. Many parents prefer to avoid these medications as they carry some risks and higher costs.

Animal therapy holds promise as a non-medicated approach to care for anxious children at the dentist — and make it a positive experience! We hope that canine therapy can provide a safe, non-medication-based approach for managing dental pain and anxiety, and possibly prevent anxiety development, so patients see their dentists regularly and have better oral and systemic health.

Tell us about the clinical trial you’re running.

Our trial investigates the effects of animal-assisted therapy on anxiety and pain in pediatric dental patients compared to a control activity. Children receive a no-cost dental exam, a cleaning, and a gift card, along with an anxiety-reducing activity. During the dental visit, the children’s heart rate and behavior are recorded, and they answer survey questions and give saliva samples, so we can study their salivary stress hormones, behaviors, and feelings during the appointment.

Have you made any discoveries thus far?

In our earlier pilot study of animal therapy, we found preliminary data suggesting that canine therapy helps to alleviate pain perceptions and reduce anxiety, particularly when kids thought about future dental visits. By reducing anticipatory anxiety, we hope kids are excited to see the dentist, go more often, and as a result have better oral health.

Our survey of child dental patients and their caregivers indicated a broad interest in animal therapy, with 75% of participants believing it would make dental experiences more enjoyable and 82% indicating that it would reduce anxiety, with little to no concern regarding safety, cleanliness, or allergies. Nearly half of them would preferentially select an office providing canine therapy.

Share an interesting story from a patient who’s participated in your clinical trial.

One patient was over the moon at the prospect of having a dog sit with him during his visit. His eyes lit up at the sight of our therapy dog, named Sugar. Because patients in this clinical trial do not know beforehand that there is the possibility of having a therapy animal companion, this came as a delightful surprise to the child. At the end of the visit, the patient was so enamored with Sugar that he expressed intense excitement to go to the dentist in the future — so much so that his parents planned to make his next appointment at a clinic offering animal therapy.

Supporting people living with HIV in Vietnam

Bill Miller and Vivian Go

Bill Miller and Vivian Go (photo by Alyssa LaFaro)

UNC Gillings School of Global Public Health researchers Vivian Go and Bill Miller are running multiple clinical trials in Vietnam to prevent HIV spread and support people living with the disease.

What is your research focus?

We do research to prevent people from getting HIV, but also help them get the care they need. We often work with people who use drugs or alcohol, helping them limit their risk of HIV or manage their infection if they already have the disease.

Tell us about the clinical trials you’re running.

We have five ongoing clinical trials. All of them are happening in Vietnam.

One that’s about to end focuses on people who inject drugs and are just starting treatment for HIV. We used short counseling sessions to help them receive the care they need and to take the medicines effectively.

Two trials testing investigational drugs are ongoing. These include evaluating a new drug for preventing tuberculosis (TB) and testing a new vaccine for hepatitis B, both in people living with HIV.

And then two new trials are just starting. One tests an intervention that helps people with HIV who drink too much alcohol. We showed previously that this intervention helps these people stay in HIV care and take their medication effectively. Our trial is taking this intervention and scaling it up to 32 clinics in Vietnam. We’re testing whether delivering that intervention using experiential learning for clinic staff helps them deliver it to their patients.

The other trial is using a similar intervention for alcohol reduction among men who have sex with men. The goal is to help them take a medicine called PrEP to reduce their HIV risk.

Have you made any discoveries thus far?

It’s too early in the process for our current trials, but a 2021 study found that long-acting injectable medication to prevent HIV infection was both safe and effective among men who have sex with men and transgender women.

What are your hopes for the future of these trials?

The biggest thing is getting the work we do into the hands of the people who can use it effectively. In our global research, that usually means collaborating with the Ministry of Health to ensure our efforts are sustained and implemented in meaningful ways in the places we are working.

We are thinking about future trials now. One of them will likely focus on helping people who are vulnerable to diseases manage the stigma that they face in their daily lives and within the health care system.

Reducing food allergies in children

Edwin Kim

Edwin Kim (photo by Alyssa LaFaro)

UNC School of Medicine researcher Edwin Kim is running multiple clinical trials to develop better treatments for people with food allergies.

What is your research focus?

Trying to come up with treatments for the growing number of people who have food allergies. The immune system is designed to fight off infections and other threats to the body. While it has protections in place to keep it controlled, it can mistakenly target things that are perfectly safe — like food, which can then cause allergic symptoms or anaphylaxis, a life-threatening reaction that often reduces breathing and induces shock.

We are studying treatments that can increase how much food a person can tolerate before having an allergic reaction, and if a reaction were to happen, decrease the severity of their symptoms.

Tell us about the clinical trials you’re running.

We are a site in the OUtMATCH study, which is designed to see if an injectable medication called omalizumab can protect against multiple food allergies, including peanuts and milk. Omalizumab specifically targets the allergic antibodies in a person’s immune system, and then removes these antibodies. We hope that it can prevent allergic reactions to these foods or, at the very least, increase how much food a person can tolerate before having a reaction to protect against accidental exposure.

We are also a site for the ALLIANCE study, which tests whether a dissolving tablet that contains a tiny amount of peanut protein can be used for sublingual immunotherapy (SLIT). The idea behind SLIT is to give small exposures of the allergen, in this case 1/75th of a peanut kernel, under the tongue once daily to reprogram the immune system to become less reactive. The amount is just enough to make it safe, but still big enough for your immune system to see and respond to.

A third study is AVX-201, which tests regular exposures to peanuts using peptide immunotherapy, given by injection. Instead of using a whole peanut, which can trigger allergic reactions, the PVX-108 medication is made of small, broken-up parts of the peanut protein called peptides that can hopefully bypass the parts of the immune system that react and go straight to the parts that build tolerance.

Share an interesting story from a patient who’s participated in your clinical trials.

In one of our earliest clinical trials of peanut sublingual immunotherapy, one young child had been taking the treatment for a couple of years. He and his parents did not know if he was receiving the actual peanut medicine or the placebo.

While his mother was driving him to an activity, he happened to find a peanut M&M in the back seat. Before she could stop the car and take it from him, he ate it. Understandably frightened, she watched him super closely and, as the minutes passed, nothing happened. At that point, she realized that he might be getting the actual peanut medication.

One year later, her hunch was confirmed when he successfully ate nearly 20 peanuts — about 50 times what usually causes a reaction — without symptoms during an oral food challenge, which is monitored by doctors in a safe environment.

What are your hopes for the future of these trials?

Food allergy is a disease where one size does not fit all. People are allergic to different foods, and their risks and reactions are different. I would like to see multiple options available for patients to choose from. And studies that compare treatments with each other — not to prove that one is the best, but to showcase the different benefits that each can provide and the risks and effort it takes to get those benefits to help patients decide which might be best for them and their situation.

Improving health for jobseekers and workers

Shawn Kneipp

Shawn Kneipp (photo by Alyssa LaFaro)

UNC School of Nursing researcher Shawn Kneipp is running a clinical trial to test interventions to reduce chronic disease risks that occur from unemployment, which includes supporting people hired into new jobs.

What is your research focus?

How chronic health conditions affect the ability of people to either become or stay employed, and how employment environments can affect health. For example, how do chronic health conditions like migraine headaches or depression interfere with the ability to find a job or maintain a full-time job?

On the flip side, what kinds of things are available in the work environment that can help people with these chronic health conditions get hired and better manage their health conditions? For example, does having a more supportive supervisor lead to better health and employment outcomes for people?

Tell us about the clinical trial you’re running.

I am currently running a clinical trial to test a “multilevel intervention” for people who are not employed but looking for work. This means we are testing interventions that target changing factors at more than one level.

In our current trial, one intervention focuses on behavior change to help jobseekers deal with the stress of unemployment, stay healthy, and avoid chronic disease. Another happens in the job they are hired into, where supervisors learn how to better support their new employees. This helps reduce employee stress and encourages healthy behaviors.

What motivates you to do this work?

I am a public health nurse and nurse practitioner who has worked with people in clinics, in residential neighborhoods, and in social services departments for many years. I’ve seen how stressful it is for people when they lose their job and don’t have resources to fall back on. Those experiences have led to the research I am doing now.

One of the most rewarding things is when study participants share how helpful an intervention was for them. When one of my earlier trials finished around 2010, I held discussion groups to talk about what they experienced. The best feeling in the world was when most of the people in the group were actually eager to participate in whatever study we were doing next. There is no better reward than that.

What are your hopes for the future of clinical trials, in general?

As many areas of research are moving in new directions, researchers are trying to engage other sectors, like housing and transportation, in clinical trials. This is often a difficult challenge that we need to have better approaches for — both in terms of study design and engagement. I would love to see more researchers work with partners in sectors outside the health care system so we can develop solutions to build healthier populations.

Andrew Satterlee is director of the Brain Slice Technology Program within Eshelman Innovation and the UNC Eshelman School of Pharmacy.

Shawn Hingtgen is a professor in the Division of Pharmacoengineering and Molecular Pharmaceutics within the UNC Eshelman School of Pharmacy, a professor in the Department of Neurosurgery within the UNC School of Medicine, and a member of UNC Lineberger Comprehensive Cancer Center.

David Kram is an associate professor in the Department of Pediatrics within the UNC School of Medicine and a member of UNC Lineberger Comprehensive Cancer Center.

Laura Jacox is an assistant professor within the UNC Adams School of Dentistry. If you have a child age 4-8 and would like to participate in her clinical trial, email jlab@unc.edu or call 984-234-1858 for more information.

Vivian Go is a professor in the Department of Health Behavior within the UNC Gillings School of Global Public Health.

William Miller is a professor in the Department of Epidemiology within the UNC Gillings School of Global Public Health.

Edwin Kim is an associate professor in the Department of Medicine and division chief for UNC Pediatric Allergy & Immunology within the UNC School of Medicine.

Shawn Kneipp is the Sarah Frances Russell Distinguished Term Professor within the UNC School of Nursing.