TrialNet, an international Type 1 diabetes (T1D) research network in which Vanderbilt University Medical Center participates, has reached a milestone, announcing that more than a quarter million people have learned their risk of developing T1D through screening.
TrialNet screening is available to family members of those diagnosed with T1D. Having a family history of the disease places individuals at a 15 times greater risk than those with no family members with T1D.
In patients with T1D, the immune system mistakenly attacks insulin-producing beta cells in the pancreas, leading to a deficiency of insulin and elevated glucose levels that contribute to organ damage characteristic of diabetes. T1D autoantibodies — proteins that mark insulin-producing beta cells for destruction — are a useful tool for identifying people at risk of developing T1D, as they are easily identified in the blood.
Their presence is the earliest sign that the autoimmune process attacking beta cells has begun. Detection of T1D autoantibodies can precede the development of clinical diabetes by months or years, depending on the age at which they develop. TrialNet can test for up to five T1D autoantibodies.
“Through TrialNet, we know whom we need to track more carefully for the development of antibodies,” said Bill Russell, MD, director of the Ian M. Burr Division of Pediatric Endocrinology and Diabetes at VUMC. “And screening isn’t age restricted, so we screen people up to age 45. I’ve had parents get screened to entice their children to do the same. In one instance, a father already had five out of five antibodies and went on to develop Type 1 diabetes.”
But the impact of TrialNet extends beyond screening patients.
Over the course of VUMC’s 18 years participating in the program, the community of T1D patients has become increasingly more engaged with research efforts. More than ever, there is an eagerness to give back to others by participating in clinical trials that could help revolutionize care for those diagnosed with or at risk of developing T1D. In such trials, TrialNet typically takes drugs already shown to be effective in treating other autoimmune diseases and seeks to determine their efficacy in treating, delaying or preventing T1D.
Spencer Mannahan, a 10-year-old patient at Monroe Carell Jr. Children’s Hospital at Vanderbilt, is participating in a TrialNet study that is looking to determine whether a treatment regimen using both rituximab and abatacept can preserve insulin production in patients newly diagnosed with T1D. Russell, one of the PIs for the study (Protocol TN-25), also treated Spencer’s father, Zach, when he was diagnosed with T1D as a child.
“It’s a little surreal that Spencer is getting treatment from Dr. Russell. It’s comforting because I know his care,” said Mannahan. “Spencer’s screening was mainly precautionary. For the first couple of years, there was nothing abnormal.”
But once Spencer was diagnosed with T1D, having a previous connection with Zach’s pediatric endocrinologist made it a no-brainer to work with Russell on treatment for Spencer’s diabetes. And as Zach has found in living most of his life with T1D, he and Spencer are not alone in living with the disease.
“It’s nice to know that it’s not just me, and I’ve got people who are going through the same thing,” Mannahan said.
Preserving insulin production is the paramount issue for most patients participating in TrialNet’s studies, including for Spencer, who is newly diagnosed. But joining a trial also has the potential to help others — and that can be a major selling point for participants.
Lauren O’Neal, a medical student at the University of Texas at Austin, is also newly diagnosed with T1D.
She enrolled in a different TrialNet study (Protocol TN-31) examining the effect of abrocitinib and ritlecitinib on insulin production in newly diagnosed individuals. While the possibility exists that her insulin production could be preserved, O’Neal joined the study because it presented an opportunity to make a positive impact on future patients.
“I was looking for clinical research trials. I’m a medical student, so I thought it would be a good opportunity to be a part of one,” said O’Neal. “At least for me, I don’t think the treatment is necessarily going to do too much, but for someone else, if we can buy them more time before onset, that would be nice.”
O’Neal was diagnosed with T1D at age 28 after going into diabetic ketoacidosis, a serious complication of diabetes when the body can’t produce enough insulin, and was connected with TrialNet to examine options for participating in a study.
“I’ve had a good time participating in the study because of the care team members,” O’Neal said. “It’s been very smooth. Everyone is very kind and responsive. Being a participant, it’s been a good experience.”
These clinical trials support TrialNet’s goal of a future without T1D. Research is underway on new methods of blocking the advance of T1D in patients with diabetes-related antibodies. One study will investigate whether T cells that have been activated against insulin can be specifically targeted, rather than issuing a treatment that targets all the body’s T cells (thus rendering the patient immunocompromised).
“The goal is to eventually have a drug that is tolerable to the patient, affordable and delays or even prevents the advancement of antibodies into a full-on diagnosis,” Russell explained. “We want a focused intervention that won’t destroy or disable healthy T cells. In this [potential] treatment, an antigen will attract and trap T cells that are already activated against insulin and smother them in naturally produced factors that calm them down, like putting a wet blanket on them.”
As research continues, Russell is confident that TrialNet’s efforts will continue serving patients and pave the way for further advancements in T1D treatment.
“Over the years, we have already begun to reset the risk equation for people predisposed to develop Type 1 diabetes,” said Russell. “Teplizumab, a drug that we investigated 14 years ago, was the first to be approved by the FDA to delay the development of clinical T1D when it is identified at a preclinical stage. We’ve engaged the community well, and there’s no question around here that when kids are diagnosed with Type 1 diabetes, we have something to offer the families that allows them to identify others at risk and be part of the long-term solution to the challenge of protecting everyone from developing the disease.”
TrialNet, the largest clinical trial network assembled to change the course of Type 1 diabetes, is funded by the National Institutes of Health through grant number NCT00097292.
