A Long Arc of Research to Prevent Type 1 Diabetes in a Pediatric Population


Pediatric Clinical Research Center waiting lounge in Mission Bay, UCSF. Photo credit: Elisabeth Fall

More than 20 years have passed since Stephen Gitelman, MD, professor of pediatrics, and Christine Torok, RN, clinical research nurse and coordinator, joined forces

to test an ambitious new drug called “Teplizumab” to tackle Type 1 diabetes among children and young adults. The study team utilized the Clinical and Translational Science Institute’s (CTSI) Pediatric Clinical Research Center (PCRC) extensively at Parnassus and now at Mission Bay for more than 22 years. The drug was created by Jeffrey Bluestone, PhD, professor of medicine, at UCSF’s Diabetes lab, which first successfully tested it in an animal model of type I diabetes. Gitelman and Torok first infused the drug in a human being in 1998.   “Now we’re phase III, but I’ve seen this drug from infancy onward,” Torok said.


“We’re interested in altering the course of Type I diabetes, which is the autoimmune destruction of insulin producing beta cells. We think Type I is in large part remediated by T cells so this is a therapy that targets T cells.  Though we started working with it over 20 years ago, today it’s one of the most promising potential therapies to protect beta cells,” said Gitelman.


There are five or six new onset trials where this drug looks promising. A NEJM paper shows it can delay the onset of diabetes and those at risk by an average of two years. [See in-depth UCSF news story on this immunotherapy https://www.ucsf.edu/news/2019/06/414631/immunotherapy-delays-type-1-diabetes-onset-people-high-risk]


The Details Matter


Infusing this drug requires time and intricate monitoring. The research team needed it to be in-patient where they watched participants for 14 days. Each day participants received  a 30-minute infusion monitored for 4 hours, and were watched overnight. Years later, the procedure has been reduced to one to two hours. “Thank goodness the PCRC had an in-patient unit at that time during the evolution of this drug – figuring out the ideal dose, timing and how many days to give it,” Torok shared.


Stephen Gitelman, MD. Photo credit: Elisabeth Fall.

During phase II of the drug’s development, it was determined that infusion time could be reduced from 14 to 12 days, with  a gradual dose increase for the first three days of infusion, then held steady after that. When the study moved to Mission Bay in 2015, Gitelman and Torok worked with the PCRC to strategize how to make a weekend infusion work, since PCRC did not usually provide weekend coverage at their new location in the Gateway building.    Fortunately, the addition of a Saturday hours by the pediatric infusion center and with the help of the adult infusion center on Sunday, PCRC and the Gitelman group were able to make it work. 


“We came to realize it could be done safely as an outpatient but it’s still quite tedious because of consecutive days which requires weekends. A lot of time and space is required by everyone to make it work. The timelines are pretty tight,” said Gitelman. The research team has to screen and enroll participants six weeks before diagnosis. “We don’t have the liberty projecting out weeks and months in advance booking the sites. We have to have flexibility and partnership with the CRC (PCRC) to use the bed space and make it happen,” added Gitelman.


“It’s more work to make a weekend work – you have to coordinate everything, the pharmacy. I’m really impressed – all the years of discussion have made this a relatively easy transition. Once we’re able to enact it, it’s been great,” said Torok. 

Drug development is a tedious, treacherous path, but this has been steadily making its way and we’re excited.

Stephen Gitelman, MD

UCSF Professor of Pediatrics


The End of the Beginning


The team has followed some of the participants out 7 or 8 years since their diagnosis. The primary impact is within the first 2 years following therapy but the team thinks there are some lingering affects even years later.


 “It’s quite a remarkable therapy, but we still think it’s early days in exploring how it may prevent diabetes, whether we can expand in the age range we offer it to.” The youngest age tested is seven to eight years old, but as they see increasing incidents of Type I diabetes in children under the age 8, they are eager to get it tested in a younger population. They hope to even be able to make it better by combining the drug with another agent. “There are a lot of directions from here,” said Gitelman.


“We refer it to the end of the beginning – a very long, slow lead in. Drug development is a tedious, treacherous path, but this has been steadily making its way and we’re excited,” Gitelman said.


Related Publications


Preventing Type 1 Diabetes in a Pediatric Population



Teplizumab (Anti-CD3 mAb) Treatment Preserves C-Peptide Responses in Patients With New-Onset Type 1 Diabetes in a Randomized Controlled Trial, 2013



JDRF Countdown magazine, Winter 2003


Insulin Needs after CD3-Antibody Therapy in New-Onset Type 1 Diabetes, 2005



Anti-CD3 Monoclonal Antibody in New-Onset Type 1 Diabetes Mellitus, 2002