Open-Label Study of Dimethyl Fumarate in Adults With Type 1 Diabetes

Official title

Non-Randomized, Parallel-Controlled, Single-Center, Open-Label Clinical Trial Evaluating the Efficacy and Safety of Dimethyl Fumarate in Preserving Pancreatic β-Cell Function in Adults With Type 1 Diabetes

Overview

This is a non-randomized, parallel-controlled, single-center, open-label clinical trial designed to evaluate the efficacy of dimethyl fumarate in preserving pancreatic beta-cell function in adults with type 1 diabetes, as well as its safety and tolerability in this population. Eligible participants are adults aged 18 to 65 years who meet the ADA 2024 diagnostic criteria for type 1 diabetes, have at least 2 positive islet autoantibodies, and have residual beta-cell function as evidenced by a random C-peptide level of at least 200 pmol/L. A total of 96 participants are planned for enrollment, including 32 in the dimethyl fumarate treatment group and 64 in the standard-treatment control group. Participants in the treatment group will receive dimethyl fumarate enteric-coated capsules in addition to standard insulin therapy for type 1 diabetes. Dimethyl fumarate will be initiated at 120 mg twice daily and increased after 7 days to a maintenance dose of 240 mg twice daily. Participants in the control group will receive standard insulin therapy alone. The intervention period will be 24 weeks, followed by 52 weeks of follow-up. The primary efficacy endpoint is the baseline-adjusted geometric mean area under the serum C-peptide curve during a 2-hour mixed-meal tolerance test at Week 24. Secondary endpoints include measures of beta-cell function at multiple time points, changes in glycated hemoglobin, proportions of participants with good or poor glycemic control, insulin dose requirements, and immunologic markers including lymphocyte subsets, cytokine profiles, and islet autoantibody characteristics. Safety assessments will include the incidence of flushing, gastrointestinal adverse events, allergic reactions, opportunistic infections, liver function abnormalities, lymphopenia, renal abnormalities, hypoglycemia, severe hypoglycemia, ketosis, and ketoacidosis. The total study duration is 36 months, from January 2026 to December 2028.

Interventions

• Drug Dimethyl Fumarate Enteric-coated Capsules
  Dimethyl fumarate enteric-coated capsules, initiated at 120 mg twice daily and increased after 7 days to 240 mg twice daily.
• Drug Insulin
  Standard insulin therapy for type 1 diabetes according to routine clinical practice.

Primary outcome measures

• Baseline-Adjusted Geometric Mean Area Under the Serum C-Peptide Curve During a 2-Hour Mixed-Meal Tolerance Test [Time frame: 24 weeks after end of intervention (48 weeks after enrollment)]

Secondary outcome measures (12)

• Baseline-Adjusted Geometric Mean Area Under the Serum C-Peptide Curve During a 2-Hour Mixed-Meal Tolerance Test [Time frame: End of intervention (24 weeks after enrollment) and 52 weeks after end of intervention (76 weeks after enrollment)]
• Change From Baseline in Geometric Mean Area Under the Serum C-Peptide Curve During a 2-Hour Mixed-Meal Tolerance Test [Time frame: End of intervention (24 weeks after enrollment), 24 weeks after end of intervention (48 weeks after enrollment), and 52 weeks after end of intervention (76 weeks after enrollment)]
• Number of Participants Maintaining Positive C-Peptide Response After a 2-Hour Mixed-Meal Tolerance Test [Time frame: 52 weeks after end of intervention (76 weeks after enrollment)]
• Glycated Hemoglobin (HbA1c) [Time frame: End of intervention (24 weeks after enrollment), 24 weeks after end of intervention (48 weeks after enrollment), and 52 weeks after end of intervention (76 weeks after enrollment)]
• Number of Participants With Poor Glycemic Control [Time frame: End of intervention (24 weeks after enrollment), 24 weeks after end of intervention (48 weeks after enrollment), and 52 weeks after end of intervention (76 weeks after enrollment)]
• Number of Participants With Good Glycemic Control [Time frame: End of intervention (24 weeks after enrollment), 24 weeks after end of intervention (48 weeks after enrollment), and 52 weeks after end of intervention (76 weeks after enrollment)]
• Average Exogenous Insulin Dose [Time frame: End of intervention (24 weeks after enrollment), 24 weeks after end of intervention (48 weeks after enrollment), and 52 weeks after end of intervention (76 weeks after enrollment)]
• Change from baseline in proportion of peripheral blood CD4+ T cells [Time frame: End of intervention (24 weeks after enrollment), 24 weeks after end of intervention (48 weeks after enrollment), and 52 weeks after end of intervention (76 weeks after enrollment)]
• Change from baseline in proportion of peripheral blood B cells [Time frame: End of intervention (24 weeks after enrollment), 24 weeks after end of intervention (48 weeks after enrollment), and 52 weeks after end of intervention (76 weeks after enrollment)]
• Change from baseline in proportion of peripheral blood natural killer cells [Time frame: End of intervention (24 weeks after enrollment), 24 weeks after end of intervention (48 weeks after enrollment), and 52 weeks after end of intervention (76 weeks after enrollment)]
• Change from baseline in proportion of peripheral blood regulatory T cells [Time frame: End of intervention (24 weeks after enrollment), 24 weeks after end of intervention (48 weeks after enrollment), and 52 weeks after end of intervention (76 weeks after enrollment)]
• Change from baseline in serum interleukin-6 concentration [Time frame: End of intervention (24 weeks after enrollment), 24 weeks after end of intervention (48 weeks after enrollment), and 52 weeks after end of intervention (76 weeks after enrollment)]

Eligibility criteria

Inclusion criteria

• Willing and able to participate in the study and provide signed informed consent
• Aged 18 to 65 years
• Diagnosed with type 1 diabetes mellitus according to ADA 2024 criteria
• Positive for at least 2 islet autoantibodies among insulin autoantibody (IAA), glutamic acid decarboxylase autoantibody (GADA), insulinoma-associated protein 2 autoantibody (IA-2A), islet cell antibody (ICA), and zinc transporter 8 autoantibody (ZnT8A)
• Random C-peptide level greater than or equal to 200 pmol/L

Note:

\- For participants who have used insulin for more than 14 days, a positive IAA result must be accompanied by at least 2 additional positive autoantibodies other than IAA

Exclusion criteria

• Pregnant or breastfeeding women, positive urine pregnancy test at screening, or inability to rule out pregnancy in the opinion of the investigator
• Good glycemic control with oral antidiabetic drugs alone
• Participation in other studies involving diabetes treatment or immunomodulation
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of normal
• Patients with renal insufficiency or evidence of renal impairment:

eGFR <60 mL/min/1.73 m²; or other renal diseases considered by the investigator to be unsuitable for study enrollment

• History of malignancy, uncontrolled immune system disease, or uncontrolled infection
• Alcohol abuse, drug abuse, psychiatric disorder, or other conditions considered unsuitable for participation in a drug trial
• Use of other immunosuppressive agents within 12 weeks before enrollment
• Participation in any other drug trial within 12 weeks before enrollment
• History of multiple drug allergies, allergic diseases, hypersensitivity constitution, or drug dependence
• Any disease or condition that, in the opinion of the investigator, may interfere with study participation or evaluation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Jiangsu Provincial Hospital — Nanjing

Identifiers

NCT: NCT07548996 · 2026-SR-107

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗