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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Baseline-Adjusted Geometric Mean Area Under the Serum C-Peptide Curve During a 2-Hour Mixed-Meal Tolerance Test
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •- 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
排除标准
- •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
研究组 & 干预措施
Dimethyl Fumarate Plus Standard Insulin Therapy
Participants in this arm 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 240 mg twice daily. The intervention period will last 24 weeks, followed by 52 weeks of follow-up.
干预措施: Dimethyl Fumarate Enteric-coated Capsules (Drug)
Dimethyl Fumarate Plus Standard Insulin Therapy
Participants in this arm 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 240 mg twice daily. The intervention period will last 24 weeks, followed by 52 weeks of follow-up.
干预措施: Insulin (Drug)
Standard Insulin Therapy
Participants in this arm will receive standard insulin therapy for type 1 diabetes without dimethyl fumarate. Participants will be followed according to the study schedule for 24 weeks of treatment observation and 52 weeks of follow-up.
干预措施: Insulin (Drug)
结局指标
主要结局
Baseline-Adjusted Geometric Mean Area Under the Serum C-Peptide Curve During a 2-Hour Mixed-Meal Tolerance Test
时间窗: 24 weeks after end of intervention (48 weeks after enrollment)
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 (MMTT).
次要结局
- Baseline-Adjusted Geometric Mean Area Under the Serum C-Peptide Curve During a 2-Hour Mixed-Meal Tolerance Test(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(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(52 weeks after end of intervention (76 weeks after enrollment))
- Glycated Hemoglobin (HbA1c)(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(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(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(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(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(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(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(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(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 tumor necrosis factor-alpha concentration(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 number of positive islet autoantibodies(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 glutamic acid decarboxylase autoantibody titer(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 zinc transporter 8 autoantibody titer(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 composite treatment-related symptomatic adverse reactions(From first dose to 52 weeks after end of intervention (up to 76 weeks after enrollment))
- Number of participants with composite hypersensitivity or opportunistic infection events(From first dose to 52 weeks after end of intervention (up to 76 weeks after enrollment))
- Number of participants with composite laboratory safety abnormalities(From first dose to 52 weeks after end of intervention (up to 76 weeks after enrollment))
- Number of participants with composite renal safety events(From first dose to 52 weeks after end of intervention (up to 76 weeks after enrollment))
- Number of participants with hypoglycemia(From first dose to 52 weeks after end of intervention (up to 76 weeks after enrollment))
- Number of participants with severe hypoglycemia(From first dose to 52 weeks after end of intervention (up to 76 weeks after enrollment))
- Number of participants with ketosis(From first dose to 52 weeks after end of intervention (up to 76 weeks after enrollment))
- Number of participants with diabetic ketoacidosis(From first dose to 52 weeks after end of intervention (up to 76 weeks after enrollment))
研究者
Yong Gu
Associate Professor, Chief Physician, Deputy Director, Department of Endocrinology
Nanjing Medical University