Researchers

TrialNet welcomes the engagement of academic investigators and industry to share ideas and knowledge in order to advance our mission of bringing disease modifying therapy to clinical use.

Ideas for Clinical Trials

TrialNet is eager to consider novel agents, combinations and study designs that help advance our mission. We accept suggestions for clinical studies, including proof of mechanism, pilot studies, and Phase 1 thru 3 trials.

TrialNet is primarily interested in receiving ideas for drugs that can be used in clinical trials to modify disease course prior to clinical onset.  Studies in new-onset disease will also be considered, providing they are a key component of the pathway towards a prevention study (e.g. provide PoC, safety, etc.).

The clinical trial concept proposal application is here.

A list of our current clinical trials is here or visit Our Research.

A list of our previously conducted clinical trials is here 

Please contact Sarah Muller if you have questions.

Important information for investigators regarding samples and data from TrialNet

TrialNet has a repository of samples from multiple intervention trials and from two observational studies aimed to understand the natural history of T1D and the response to therapy. Many of these samples were provided to individual investigators to address specific high priority scientific questions. This led to a number of important observations (reviewed in Battaglia, et al., Diabetologia, 2017). The precious nature of the remaining samples in our inventory has necessitated a change in our approach. To fully take advantage of this unique collection of samples from our well-characterized study subjects, sample release will now be part of a broad-based and collaborative team effort involving investigators within and external to TrialNet. 

As a framework for collaboration, TrialNet is creating Key Questions to prioritize using samples and data from our studies to understand the natural history of T1D progression.   Please note that TrialNet is unlikely to release samples from at-risk individuals that can be addressed using data from Key Question studies using samples from observational studies.  Thus, before submitting a proposal, please review the information below.  Similarly, if you are interested in samples from our clinical trials, we have a detailed and prioritized mechanistic plan for sample use.  Please contact Sarah Muller or Peter Gottlieb to learn more about plan details.

The Collaborative Mechanistic Studies Panel (CMSP) is coordinating the Key Question process and invites other investigators to work with us.  The first Key Question is described below.  We are planning to undertake further Key Question studies including progression from 1 to 2 autoantibodies, addressing why subjects in our intervention trials fail immunotherapy, etc.  New questions are welcome.  Please contact Sarah Muller or Peter Gottlieb with suggestions. 

Key Question 1: How to understand immune markers that predict or are associated with disease progression. (This is an ongoing study. Our goal is to make the initial data set available to the research community in 2021.)

  • This is a retrospective case: control study involving longitudinal samples from antibody positive individuals who developed T1D within 3 years (n = 89) and antibody positive individuals who did not progress during that time matched for key characteristics such as age (n = 89). A total of 556 samples are being tested in Drs. Eoin McKinney, Adeeb Rahman and Dirk Homann’s laboratories. 
  • The McKinney lab is performing bulk RNA-Seq on PBMC samples sorted into the following immune cell subsets: memory CD4+ T-cells, memory CD8+ T-cells, memory B-cells, Tregs, monocytes, NK cells, plasmablasts, cDCs, pDCs and bulk PBMCs. 
  • Data from the memory CD4+ and CD8+ T-cell subsets will be available in the study’s initial data release.
  • The Rahman lab is performing high dimensional mass cytometry (CyTOF) to extensively phenotype PBMCs using three separate panels each consisting of >35 markers. 
  • The complete data set will be available in the study’s initial data release.    

Several analytical approaches to evaluate the study data are planned.

For more details about the CyTOF markers or other aspects of this study design and testing, please contact Sarah Muller or Peter Gottlieb. 

If you wish to submit a proposal for use of TrialNet samples, please complete a Stored Sample Concept Proposal application here.

Exploratory Assays Living Biobank Proposals

TrialNet welcomes investigators who have mechanistic study proposals involving fresh blood samples from one, or at most a few, TrialNet sites.  All such “living biobank” studies must have the concurrence of the clinical site PIs and must not require other support from TrialNet.  This mechanism is most appropriate for more exploratory studies.

These proposals will be reviewed according to TrialNet priorities and to evaluate impact on subject and site burden (i.e. blood volume and shipping/handling requirements).  Studies that involve very low impact on subjects and centers (e.g., involving a single center) are frequently approved.

The Exploratory Assays Living Biobank application is available here.
 

Analysis and Publication of Existing Data

TrialNet’s publication committee welcomes ideas for analysis and publication of existing TrialNet data. Link to TrialNet publications here, access the NIDDK data-repository, and apply for data access.

Investigators are encouraged to discuss ideas with TrialNet Publication Committee, trialnetpublications@epi.usf.edu, before submitting an application to the publications committee.

The application for data access, analysis and proposed publication is coming soon. 

Investigators are also encouraged to access the NIDDK data-repository website.  Data from TrialNet studies is available directly through that resource. 

Study Name Enrollment Status Description
Rituximab-pvvr / Abatacept Newly Diagnosed Study (T1D RELAY) Currently Not Enrolling TrialNet is testing rituximab-pvvr and abatacept in people (ages 8-45) who were newly diagnosed with type 1 diabetes (T1D) to learn if using both treatments, one after the other, maintains the body’s ability to make insulin. By adding abatacept after rituximab-pvvr, researchers predict more people will experience prolonged beta cell function during and possibly after treatment.
JAK Inhibitors Newly Diagnosed Study (JAKPOT T1D) Currently Enrolling TrialNet researchers are testing two different treatments – abrocitinib and ritlecitinib – to see if either or both can preserve insulin production in people (ages 12-35) newly diagnosed with type 1 diabetes (Stage 3 T1D). Abrocitinib and ritlecitinib are in a new class of autoimmune treatments called Janus kinase (JAK) inhibitors.
ATG Prevention Study (STOP-T1D) Closed TrialNet is testing a low dose of the immunotherapy drug anti-thymocyte globulin (ATG) to see if it can delay or prevent type 1 diabetes (T1D) in people ages 6 to 34 who have a 50% risk of clinical diagnosis (Stage 3) within 2 years. Risk is defined by having two or more autoantibodies and abnormal blood sugar (Stage 2), plus at least one high-risk marker (based on test results). In an earlier TrialNet study for people newly diagnosed with T1D, low-dose ATG preserved insulin production and improved blood sugar control for 2 years.
Tolerance Using Plasmid (TOPPLE) Study: Phase 1 Currently Not Enrolling TrialNet is testing the safety of a new treatment, NNC0361-0041, in adults diagnosed with type 1 diabetes (T1D) in the past 48 months. This is a Phase 1 study, which means it is the first time this treatment is being tested for safety in people. If this study results in no safety concerns, we plan to conduct a larger study to see if this same treatment can slow down or stop T1D in people at high risk, before clinical diagnosis.
Pathway to Prevention Currently Enrolling If you or your child has tested positive for type 1 diabetes related autoantibodies, we’re here for you.
Teplizumab Prevention Study Completed We tested the drug teplizumab to see if it could delay or prevent progression of early stage T1D (stage 2) and prevent clinical diagnosis (stage 3). In earlier studies in people newly diagnosed (stage 3), teplizumab helped to prolong insulin production.
Oral Insulin Prevention Study Completed TrialNet tested the drug Oral Insulin to see if it can delay or prevent T1D (stage 1) from progressing to stage 2 and ultimately prevent clinical diagnosis (stage 3).
Hydroxychloroquine (HCQ) Completed We are testing the drug hydroxychloroquine (HCQ) to see if it can delay or prevent early stage T1D (stage 1) from progressing to abnormal glucose tolerance (stage 2) and ultimately prevent clinical diagnosis (stage 3). HCQ is already used to reduce symptoms and progression of other autoimmune diseases, such as rheumatoid arthritis and lupus. This is the first study to see if it can prevent or delay T1D.
ATG/GCSF New Onset Study Completed ATG/GCSF was designed to build on prior findings of a pilot study suggesting thymoglobulin (ATG) combined with pegylated granulocyte colony stimulating factor (GCSF) preserved insulin production for more than 1 year after treatment in people who had type 1 diabetes for 4 months to 2 years.
Abatacept Prevention Study Completed TrialNet tested the drug abatacept to see if it could delay or prevent stage 1 T1D (two or more diabetes-related autoantibodies, but normal blood sugar) from progressing to stage 2 (abnormal blood sugar) or to stage 3 (clinical diagnosis). In an earlier study in people newly diagnosed (stage 3), participants treated with abatacept had 59% better insulin production and a 9.6-month average delay in progression of insulin loss compared to those who received placebo. That difference extended out to 3 years.
Pathway to Prevention Currently Enrolling If you have a relative with T1D, you may be eligible for risk screening that can detect the early stages of T1D years before symptoms appear.
Monitoring Currently Enrolling Depending on your risk screening results, you may be eligible for monitoring. We’ll monitor you for disease progression and let you know if you become eligible for a study.
Long-Term Investigative Follow-Up in TrialNet (LIFT) Currently Enrolling If you are diagnosed with T1D while participating in one of our prevention studies, we’re still here for you. You can continue to receive personal monitoring while helping us learn more.