Objective
The primary objective of this pilot study is to evaluate the safety and tolerability of oral diroximel fumarate (DRF) in adolescents and young adults with recently diagnosed type 1 diabetes (T1D). Although several immunomodulatory therapies have been tested in new-onset T1D, durable preservation of β-cell function remains elusive, and exogenous insulin therapy continues to be the standard of care. Repurposing immunomodulatory agents with established safety profiles in other autoimmune diseases represents a promising strategy to accelerate translation into T1D.
DRF is an oral fumaric acid ester approved for the treatment of relapsing-remitting multiple sclerosis (RRMS), where it has demonstrated sustained safety and immunomodulatory effects. Given the shared autoimmune features of RRMS and T1D, DRF may modulate immune pathways relevant to β-cell destruction while offering the convenience of oral administration. This single-center, open-label pilot study will enroll up to 12 individuals aged 12-35 years within 100 days of T1D diagnosis and administer DRF for six months, using a dose-escalation strategy to optimize tolerability.
The study is designed to generate essential safety, feasibility, and mechanistic data rather than to establish clinical efficacy. Longitudinal clinical assessments and immune profiling will provide preliminary insight into whether DRF engages immune pathways implicated in early T1D and will inform the design of future randomized trials aimed at preserving endogenous insulin secretion.
Background Rationale
Type 1 diabetes (T1D) is a lifelong autoimmune disease in which the body’s immune system attacks and destroys the insulin-producing cells of the pancreas. Loss of insulin production leads to uncontrolled blood glucose and acute complications such as diabetic ketoacidosis, as well as long-term risks including cardiovascular disease, kidney failure, vision loss, and neuropathy. Although insulin therapy and glucose monitoring have improved outcomes, they do not address the underlying autoimmune process or prevent progressive β-cell loss. Preserving residual β-cell function early in T1D therefore remains a major research goal.
Many immune-based interventions in T1D have focused on short courses of antibody therapies. While some have demonstrated transient preservation of insulin secretion, benefits often diminish over time, prompting interest in alternative strategies capable of sustained immune modulation. Repurposing therapies already approved for other autoimmune diseases is particularly attractive, as their safety profiles and mechanisms of action are well characterized.
Diroximel fumarate (DRF) is an oral therapy approved for relapsing-remitting multiple sclerosis (RRMS). Along with its related compound dimethyl fumarate (DMF), DRF modulates innate and adaptive immune responses and reduces inflammatory signaling. DRF was specifically developed to maintain biological activity while improving gastrointestinal tolerability compared with earlier fumarate formulations.
Preclinical studies, including work from our group, suggest fumaric acid esters may also be effective in autoimmune diabetes. In the non-obese diabetic (NOD) mouse model, DMF treatment both prevented diabetes onset and reversed hyperglycemia in newly diabetic animals, with associated reductions in inflammatory immune activity and preservation of insulin-producing cells. These findings provide mechanistic justification for testing fumarates in human T1D.
Because DRF is already approved for human use and administered orally, it represents a practical and promising candidate for evaluation in T1D. The current pilot study will assess the safety and feasibility of DRF in adolescents and young adults shortly after diagnosis, a period when meaningful residual β-cell function often remains. In addition to safety, exploratory metabolic and immune measures will be collected to inform the design of future trials.
In summary, this study leverages extensive clinical experience with fumarates in multiple sclerosis and strong preclinical evidence to explore a patient-friendly immunomodulatory approach in early T1D.
Description of Project
Type 1 diabetes (T1D) is an autoimmune condition in which the body’s immune system mistakenly destroys the insulin-producing cells in the pancreas. Without insulin, people with T1D must rely on daily injections or pumps to manage blood sugar. Although technologies for insulin delivery and glucose monitoring have improved, there is still no widely effective therapy that preserves natural insulin production after diagnosis. New approaches are needed to slow the autoimmune process early in the disease.
This pilot study explores the safety and feasibility of an oral medication called diroximel fumarate (DRF) in adolescents and young adults with newly diagnosed T1D. DRF is related to a drug that has been used safely for many years to treat relapsing-remitting multiple sclerosis (RRMS), another autoimmune disease. Because both RRMS and T1D involve immune system dysfunction, researchers are investigating whether DRF may help reduce harmful immune activity in T1D.
Unlike many immune therapies that require injections or infusions, DRF is taken by mouth, making it easier to use. In people with RRMS, DRF alters immune cell behavior and reduces inflammation. Early laboratory studies in animal models of T1D suggest that related compounds can reduce autoimmune damage and preserve insulin production in some cases.
Twelve participants aged 12-35 years who were diagnosed with T1D within the past 100 days will take DRF orally for six months. Participants will begin with a lower dose for the first week to improve tolerability before increasing to the full dose. Throughout the study, participants will be closely monitored to ensure safety and adherence to study procedures.
The main goal of this study is to determine whether DRF is safe and well tolerated in people with new-onset T1D. Safety assessments include physical examinations, blood tests, and monitoring for side effects. Although this pilot study is not designed to prove that DRF stops or reverses T1D, researchers will collect preliminary information on insulin production and immune activity using established metabolic and laboratory tests.
The study also includes genetic and immune analyses to help interpret individual responses and guide future research. Participants will attend regular clinic visits over a 12-month period under careful medical oversight. This pilot study represents an important first step toward evaluating whether an oral immune-modulating therapy like DRF could help preserve insulin production and improve long-term outcomes for people with type 1 diabetes.
Anticipated Outcome
This pilot study will examine whether an existing oral medication, diroximel fumarate (DRF), can be safely and tolerably used in adolescents and young adults who have been recently diagnosed with type 1 diabetes (T1D), and whether its use provides early biological signals relevant to disease progression. DRF is approved for relapsing-remitting multiple sclerosis (RRMS), another autoimmune disease, and has a well-established safety profile. Interest in DRF for T1D is supported by shared immune mechanisms between these conditions and encouraging results from animal studies showing reduced autoimmune inflammation and preservation of insulin-producing cells.
The primary goal of the study is to assess the safety, tolerability, and feasibility of administering DRF over six months in individuals with new-onset T1D. Safety will be closely monitored through adverse event reporting and laboratory testing, while feasibility will be evaluated through recruitment, retention, adherence, and visit completion. These data will help determine whether larger studies are practical.
In addition to safety and feasibility, the study will collect early metabolic and immune data to explore biological activity. A key outcome will be measurement of c-peptide responses to a meal challenge, which reflects the body’s remaining ability to produce insulin. Although the study is not designed to prove clinical benefit, these measurements will provide early insight into whether DRF may influence β-cell function.
Blood samples will also be analyzed to explore how DRF affects immune pathways involved in T1D, including immune cell populations, inflammatory signaling molecules, and genetic risk patterns. These exploratory analyses are intended to generate hypotheses and guide future trial design rather than to establish definitive efficacy.
Overall, the anticipated outcome is a comprehensive assessment of DRF’s safety and tolerability in new-onset T1D, along with preliminary biological signals that may justify larger, controlled studies. Even if definitive benefit is not demonstrated, the results will inform next steps toward developing therapies aimed at preserving insulin production and improving long-term outcomes for people with T1D
Relevance to T1D
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by immune-mediated destruction of insulin-producing β cells, resulting in lifelong dependence on exogenous insulin and increased risk of long-term microvascular and cardiovascular complications. Despite advances in insulin delivery and glucose monitoring, current therapies do not address the underlying autoimmune process, and preservation of residual β-cell function remains an unmet need.
This pilot study evaluates diroximel fumarate (DRF), an oral immunomodulatory therapy approved for relapsing-remitting multiple sclerosis (RRMS), in adolescents and young adults with newly diagnosed T1D. DRF and related fumaric acid esters have a well-established safety profile in RRMS and modulate immune pathways implicated in autoimmunity, making them attractive candidates for repurposing in T1D. Preclinical studies, including work from our group, suggest fumaric acid esters may also be effective in autoimmune diabetes and preserve β-cell function.
Approximately 12 participants aged 12-35 years within 100 days of T1D diagnosis will receive DRF for six months, with close monitoring for safety, tolerability, and feasibility. While the study is not designed to demonstrate clinical efficacy, longitudinal metabolic testing and immune profiling will generate preliminary biological signals and mechanistic insights. These data will inform the design of future randomized trials and help determine whether DRF is a safe and feasible candidate for disease-modifying strategies in early T1D.