Objective
We will determine the safety, optimal dose and efficacy of a drug commonly used to treat psoriasis, ustekinumab, for slowing or preventing beta cell loss in individuals who have recently been diagnosed with T1D. .
Background Rationale
Previous studies in animal models and in individuals with T1D have shown that two types of immune T cells work together to destroy insulin-producing pancreatic beta cells. Currently, a drug (ustekinumab) exists that is known to block the activation of these two T cell types. Ustekinumab is currently licensed for the treatment of psoriasis and Crohn’s disease, where it has proven to be both safe and effective. We would like to test ustekinumab in subjects with recent-onset T1D to determine its safety and efficacy.
Description of Project
In type 1 diabetes (T1D), cells from the immune system called T cells attack and destroy insulin-producing beta cells leaving affected individuals with a lifelong dependence on insulin. Even with insulin injections, blood glucose control is imperfect, leading to an increased risk of complications from chronic hyperglycemia and a shortened life span. In preliminary work, we have demonstrated that a biologic drug (an antibody known as ustekinumab) that inhibits inflammation can be safely administered to young adults with new onset diabetes. Ustekinumab is currently licensed for use in psoriasis and, in higher doses, in Crohn’s disease where it has proven to be both highly effective and safe.
We propose a phase II/III trial to test the ability of ustekinumab to halt the progression of T1D in adults with recent-onset T1D. 60 young adults with new onset (within 100 days of being diagnosed) T1D will be randomly assigned to receive the drug or a placebo for 1 year and the progression of damage to the pancreas will then be followed. In our first study we found that this drug can decrease inflammatory proteins, specifically IFN-gamma and IL-17, that are thought to damage islets. We believe that if these proteins can be blocked soon after the development of diabetes, then the remaining insulin-producing cells in the pancreas may be protected, and regenerate. This would allow production of sufficient insulin so that individuals may be insulin free, or require less insulin. As a second part of the study, we will assess the ability of the drug to block the activity of the harmful immune cells that produce inflammatory cytokines and damage the islets. Overall our proposal will test the safety and efficacy of using ustekinumab to improve the outcomes for individuals with recent onset T1D.
Anticipated Outcome
We anticipate that doses of ustekinumab used for the treatment of Crohn’s disease will be safe in T1D subjects, as it has been in patients with Crohn’s disease. We also believe that ustekinumab will prevent T cells from harming beta cells, and possibly reduce the need for insulin and preserve endogenous insulin secretion. .
Relevance to T1D
This project is highly relevant to T1D as it tests a potential drug therapy that may preserve beta cell
function and insulin secretion.