Claire: A Lifetime of Contributing to the Science of Type 1 Diabetes Prevention
For Claire and her mother, Correne, type 1 diabetes has always been a part of their lives, even though neither has been diagnosed. Several of their close relatives have the disease, and when Claire was 4 years old, she and her family received the sobering news that she was at risk of developing type 1 diabetes as well. However, that knowledge has also enabled Claire, now age 13, to spend most of her life participating in clinical research, including a clinical trial aiming to halt type 1 diabetes before symptoms can occur.
“I think it’s really important to contribute to science,” Claire says, when asked what she’d tell others thinking of participating in a clinical trial. “Even though there are challenges … they are all definitely worth it.”
Living in the Shadow of Type 1 Diabetes
Family members on both sides of Claire’s family tree live with type 1 diabetes. “We just grew up with type 1 [diabetes] in our family,” Correne says. At family gatherings, everyone knows what to do if someone with the disease has an episode of dangerously low blood glucose (sugar). For Correne, a pediatrician, type 1 diabetes also affects her professional life: she diagnoses patients with the disease in her own practice. One New Year’s Day, she even noticed that a visiting family member was abnormally thirsty at breakfast—an observation that led to a type 1 diabetes diagnosis. “Type 1 diabetes is so personal for our family because it just has had a huge impact on our lives,” Correne says.
It was also family that brought Correne and Claire to NIDDK’s Type 1 Diabetes TrialNet, an international clinical research network aimed at discovering ways to delay or prevent type 1 diabetes. When a family member was dropping her daughter off at diabetes camp, she noticed that TrialNet was recruiting participants from families of people with type 1 diabetes. She asked Correne if her family would be interested in enrolling. Correne’s response was, “Sure! Anything we can do.”
So began the summer tradition of what the family called “pokey parties,” where Claire, her brother Henry, and other young children in their extended family would visit the diabetes camp to have their blood drawn so they could be screened for risk of type 1 diabetes. The “poke” was not popular with Claire, who was not a fan of needles, but there were prizes afterwards, and since the kids did it together, the sense of camaraderie helped.
The risk of developing type 1 diabetes can be determined through blood tests, like those Claire and Henry volunteered for. In particular, their blood samples were tested for the presence of diabetes autoantibodies. These autoantibodies are proteins produced by the body that indicate the immune system is attacking the insulin-producing beta cells of the pancreas, and their appearance in the blood means that the person has an increased risk of developing type 1 diabetes in the future. That risk rises as the number of different types of diabetes autoantibodies rises.
When Claire was 4 years old, they got a phone call from TrialNet study staff. Claire had tested positive for one of the autoantibodies. With this sobering news, though, came a new opportunity: would they be interested in participating in a bit more testing and surveillance of Claire’s health?
The family agreed, and so from age 4 until age 9, in addition to blood draws, every 6 months Claire took an oral glucose tolerance test that measured her body’s ability to metabolize the sugar glucose. Claire dreaded these tests, because they required more needles: an intravenous (IV) line (or “straw shot” as she and her family took to calling it) in her arm. Participating in TrialNet, though, gave her and her family a front-row seat to how Claire’s health was changing. By the time she was 9, Claire’s blood tests indicated that she had four different diabetes autoantibodies, a sign that the autoimmune attack on her pancreas was well underway, and the results of her oral glucose tolerance tests indicated that her body’s ability to manage her blood sugar was fluctuating.
“Type 1 diabetes is so personal for our family because it just has had a huge impact on our lives,” says Correne, whose daughter Claire participates in type 1 diabetes research.
Claire remembers, when she first joined TrialNet, her mother telling her that she had “special blood” and that she might help find a cure for type 1 diabetes someday. As the number of diabetes autoantibodies in her blood rose, Claire says, “I didn’t really understand what the antibodies were doing, but I knew that somehow it was related to the possibility that I would get this disease.” Once she developed the fourth antibody, the possibility that she might be diagnosed with type 1 diabetes became more real to her.
Meanwhile, Claire’s parents could only watch from the sidelines, because there weren’t any treatments known to prevent type 1 diabetes or halt its progression. Once Claire had four autoantibodies in her blood, her risk of developing symptoms of type 1 diabetes in the next year or two was very high. Correne says, “At that point we had kind of resigned ourselves … it’s coming.”
Then, her family received another call from TrialNet staff. TrialNet was recruiting for a clinical trial, and Claire might be eligible to enroll. Would the family be interested in learning more about a prevention trial? “Yes,” Correne answered. “Absolutely.”
Discussing Risks and Hoping for Rewards
The prevention trial, Claire and her family learned, would be testing a drug called teplizumab (also known as “anti-CD3”). Teplizumab targets the immune system and had been shown previously to slow the loss of beta cells in people recently diagnosed with type 1 diabetes. Now researchers wanted to test whether the treatment could prevent clinical onset of type 1 diabetes. To investigate this, they were recruiting relatives of people with type 1 diabetes who did not yet have the disease themselves but who were at high risk of developing it…like Claire.
Taking part in the trial would be a big commitment. The study site at Yale University was hours away from their home, and the trial would involve an IV infusion daily for 14 days and additional trips for follow up. Also, there was a risk that the drug could cause short- or long-term side effects. Finally, due to the trial design (which would randomly assign participants to either inactive placebo or teplizumab treatment so the two could be compared), Claire might not receive the drug if she was in the placebo arm of the trial, something she and the research staff would not know until the end of the study. Claire hoped she’d receive the treatment, and that it would help prevent type 1 diabetes, but there was no guarantee that either would be the case.
Whether or not to participate was a family decision. Claire’s parents discussed the pros and cons from all angles. They and their extended family also gave then-9-year-old Claire information about the study, its goals, and its importance. “It was a really tough conversation, to kind of come to a consensus that we wanted to do this,” Correne says. “We were excited that they were doing a prevention trial, but there was a lot of thought that went into making that decision [to enroll].”
In the end, the family agreed to participate. Correne explains, “We need randomized trials. We need good data … to make sure that we’re moving in the right direction for patients.” Also, she says, “From a mom standpoint … you’ll do anything, you know? If you think that it may help.”
Taking Part in the Ups and Downs of Clinical Research
In December of 2015, Correne and Claire traveled to New Haven, Connecticut, where they would stay for 2 weeks. Each day, Claire and Correne headed to the research hospital early in the morning, and the staff performed preliminary blood tests to ensure that Claire’s organs were functioning normally and that she was still eligible for the trial. Then she received an infusion over an hour or two, and by lunch they were done for the day. Claire generally felt fine after the infusions, and they would often spend the rest of the day exploring New Haven. As time passed, Claire got used to the routine.
Claire, a volunteer in the Type 1 Diabetes TrialNet network, encourages others to participate in clinical research. “Even if it doesn’t end up benefitting them, it’ll benefit others, and will definitely contribute to science.”
Correne praised the TrialNet research staff and nurses that they interacted with. “They were phenomenal. They were just outstanding.” The nurses were both efficient and caring, always trying to accommodate the trial participants’ preferences, answering any questions they had, and even suggesting things to do around town. “They went above and beyond to take care of Claire and meet her needs,” Correne says.
Despite the support, Correne says that accompanying Claire during the trial was an emotional experience. “It was just overwhelming … you’re sitting there, and you’re just watching stuff go through this [IV] tube, and just worrying, you know? ‘Am I doing the right thing?’”
Then, around day 11, Claire began feeling unwell. On day 13, after her morning blood tests, the TrialNet staff informed Claire that her liver function, though not alarming, was no longer within the range needed to continue in the trial. Though this change was not necessarily related to the experimental treatment she was receiving, she was not eligible to receive the final two planned infusions.
Correne and Claire were disappointed, and as they headed home, they wondered: had Claire been in the group receiving the experimental treatment after all? If so, did she get enough of the drug to have an effect?
Waiting, and Hoping for Good News
Life resumed for Claire and Correne, and TrialNet study personnel continued to monitor Claire’s health via regular blood tests and oral glucose tolerance tests. As the years passed and the trial’s follow-up continued, no news was good news: despite her still having the diabetes autoantibodies that statistically give her a high chance of developing the disease, Claire did not show clinical symptoms of type 1 diabetes.
Then, the day that the teplizumab trial’s results were published in June of 2019, Claire’s family received the good news they had been waiting for: the study Claire had participated in had demonstrated that teplizumab could delay diagnosis of clinical type 1 diabetes by 2 or more years among people who were at high risk. Furthermore, Claire was part of the 57 percent of trial participants who received teplizumab and had not developed type 1 diabetes by the time the trial’s results were analyzed. In comparison, only 28 percent of those who received placebo had not developed type 1 diabetes at the same timepoint. These results provided the very first evidence that clinical type 1 diabetes can be delayed with early preventive treatment. This breakthrough was only possible because of the dedication of clinical trial participants such as Claire. Their willingness to be randomly assigned to groups receiving either placebo or teplizumab treatment was critical, since participants in both groups were key to the trial’s success.
The family was excited by these results and also by the confirmation that Claire had received teplizumab. Claire was happy that the results had been so positive: “I was just glad it worked.” She believes that it’s important to help move the science forward and feels that her participation in the teplizumab trial was a great way to do that. “All I had to do was get poked by needles,” she says, a smile in her voice.
Despite her daughter Claire being still at risk for developing type 1 diabetes even after her participation in a Type 1 Diabetes TrialNet network study, Correne says, “Every day without diabetes? It’s a gift.”
Claire has also signed up for a TrialNet follow-up study that will continue to monitor her health and the effects of the teplizumab treatment, including how long its effects last. She encourages others to participate in clinical research as well. “Even if it doesn’t end up benefitting them, it’ll benefit others, and will definitely contribute to science.” Correne agrees: “I would do it again. And I would do more studies, or whatever they ask because … there’s such value in it.”
Both of them also continue to think about the future, and about others with type 1 diabetes. “It kills me when I have to make a new diagnosis of diabetes for my patients,” Correne says. Given her family history, helping to find a new treatment or even a way to eliminate the disease would be a huge personal victory. Claire also looks forward to new ways to delay, prevent, and cure the disease, especially when she sees family members treating their type 1 diabetes.
Changing What You Can
Correne and Claire understand, though, that even with the successes of the teplizumab trial, their struggle with type 1 diabetes may not be over. When they were interviewed for this article, 42 months from Claire’s first teplizumab infusion, Claire was still type 1 diabetes-free. However, it’s not clear if the treatment Claire received can halt type 1 diabetes progression permanently or if it has only delayed onset of the disease. To this day, when Claire sees family members injecting insulin or managing their insulin pumps, she says, her thoughts turn to the possibility that she might have to do the same, one day.
That, Correne and Claire say, was something they understood from the beginning: that there were no guarantees. When asked how they feel about how Claire might—despite the needles, travel, and other worries of the trial—still be diagnosed with type 1 diabetes, Correne takes a deep breath. “Every day without diabetes? It’s a gift.” She thinks back to when Claire was 9, and they were expecting her to develop type 1 diabetes in the next year or two. “Where she’s at now, and the childhood that she’s gotten to enjoy…. It’s just a gift.”
Claire is now in eighth grade, her spare time often taken up by dancing, musical theater, and oil painting. She is thinking about studying anthropology and medical illustration in college, and she would like to attend Yale.
Her participation in TrialNet has made Claire a little more positive about things that she can’t change. “I can’t change the fact that I might get [type 1] diabetes,” she says, but “even a prevention that might wear off in a few years is still great.” And despite all the things she can’t change, Claire continues to change what she can, for others and for herself. She and other clinical research volunteers make type 1 diabetes prevention trials possible, and through their efforts our understanding of how to prevent this disease is changing, one day at a time.
This content is provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. The NIDDK translates and disseminates research findings to increase knowledge and understanding about health and disease among patients, health professionals, and the public. Content produced by the NIDDK is carefully reviewed by NIDDK scientists and other experts.