A Single-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial Evaluating the Efficacy and Safety of Dimethyl Fumarate in Preserving Islet β-Cell Function in Patients With Type 1 Diabetes Mellitus
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Baseline-adjusted geometric mean area under the serum C-peptide curve (C-peptide AUC) during a 2-hour mixed-meal tolerance test (MMTT) 24 weeks post-intervention.
研究概览
简要总结
Purpose of the Clinical Trial:
This clinical trial aims to investigate whether dimethyl fumarate can treat adults with newly diagnosed type 1 diabetes and to evaluate the safety profile of dimethyl fumarate.
Primary Research Questions:
Does dimethyl fumarate protect pancreatic beta-cell function in adults with newly diagnosed type 1 diabetes? What medical issues may arise in individuals taking dimethyl fumarate?
Study Design:
Researchers will compare dimethyl fumarate with a placebo (an identical substance without active ingredients) to determine whether Dimethyl fumarate can effectively treat type 1 diabetes.
Participant Activities:
Take dimethyl fumarate or placebo orally twice daily for 24 weeks. Attend on-site visits every 4 weeks during the intervention period and every 12 weeks after the intervention for examinations and assessments.
Record symptoms, blood glucose control, islet function, and insulin usage throughout the trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Subjects who provide written informed consent.
- •Aged 18-65 years.
- •Diagnosed with Type 1 Diabetes Mellitus (per ADA 2024 criteria).
- •Positive for ≥2 autoantibodies: Insulin autoantibody (IAA) Glutamic acid decarboxylase autoantibody (GADA) Protein tyrosine phosphatase antibody (IA-2A) Islet cell antibody (ICA) Zinc transporter 8 autoantibody (ZnT8A) Note: For IAA-positive subjects with insulin use >14 days, ≥2 additional autoantibodies must be positive.
- •Disease duration ≤100 days post-T1DM diagnosis.
- •Random C-peptide ≥ 200 pmol/L.
排除标准
- •Pregnancy, lactation, or women of childbearing potential not using contraception.
- •Well-controlled glycemia with oral hypoglycemic agents alone.
- •Participation in other diabetes/immune-modulating trials.
- •ALT/AST >3× upper limit of normal (ULN).
- •History of malignancy, uncontrolled autoimmune disorders, or active infections.
- •Alcohol/drug abuse, psychiatric disorders, or conditions unsuitable for trial participation.
- •Use of immunosuppressants within 12 weeks prior.
- •Participation in other drug trials within 12 weeks prior.
- •History of drug allergies, hypersensitivity, or drug addiction.
- •Any condition deemed by investigators to compromise study integrity.
研究组 & 干预措施
Dimethyl fumarate Arm
The dosing regimen for Dimethyl fumarate enteric-coated capsules initiates at 120 mg twice daily (bid). After 7 days, the dose should be escalated to the maintenance level of 240 mg bid. This investigational product is administered concurrently with standard insulin therapy for glycemic control in Type 1 Diabetes Mellitus (T1DM).
干预措施: Dimethyl Fumarate Enteric-coated Capsules (Drug)
Placebo Arm
The placebo capsules initiate at a dosage of 120 mg twice daily (bid). After 7 days, the dose should be increased to the maintenance level of 240 mg bid, administered concomitantly with standard insulin-based antihyperglycemic therapy for Type 1 Diabetes Mellitus (T1DM).
干预措施: Matching placebo capsules (Drug)
结局指标
主要结局
Baseline-adjusted geometric mean area under the serum C-peptide curve (C-peptide AUC) during a 2-hour mixed-meal tolerance test (MMTT) 24 weeks post-intervention.
时间窗: Post-intervention Weeks 24
Participants will consume a standardized liquid meal containing fixed amounts of carbohydrate, fat, and protein. Following consumption, blood glucose, C-peptide, and glucagon levels will be measured at 0-, 30-, 60-, 90-, and 120-minute time points over a 2-hour period.
次要结局
- Changes from baseline in the geometric mean area under the C-peptide curve (AUC-C-peptide) during the 2-hour Mixed-Meal Tolerance Test (MMTT) at Intervention Week 24 and at Weeks 24 and 52 after the end of the intervention.(Intervention Week 24, and Post-intervention Weeks 24 and 52)
- Glycemic Control Status(Intervention Week 24, and Post-intervention Weeks 24 and 52)
- Incidence Rates of Anaphylaxis, Angioedema, and Opportunistic Infections(Week 4, 8, 12, 16, and 24 During Intervention)
- Mean Daily Dose of Exogenous Insulin Used During the 7 Days Preceding Each Study Visit(Intervention Week 24, and Post-intervention Weeks 24 and 52)
- Incidence Rates of Hypoglycemia/Severe Hypoglycemia and Ketosis/Diabetic Ketoacidosis (DKA)(Baseline, Weeks4, 8, 12, 16, 20 and 24 During Intervention, and 12, 24, 36, and 52 Weeks After Intervention)
- Incidence Rates of Flushing, Abdominal Pain, Diarrhea, Nausea, Vomiting, Pruritus, Rash, Proteinuria, Erythema, and Dyspepsia(Week 4, 8, 12, 16, and 24 During Intervention)
- Incidence Rates of Elevated Aspartate Aminotransferase (AST), Elevated Total Bilirubin (TBIL), and Lymphocytopenia(Week 4, 8, 12, 16, and 24 During Intervention)
- Baseline-adjusted geometric mean area under the curve (AUC) for serum C-peptide during a 2-hour mixed-meal tolerance test (MMTT) at 24 weeks of intervention and 52 weeks after the end of intervention.(Week 24 of intervention and 52 weeks post-intervention)
- The number of subjects who remained C-peptide positive at 52 weeks after the end of intervention (defined as a stimulated peak serum C-peptide concentration >= 200 pmol/L during a 2-hour MMTT).(Post-intervention Week 52)
- Immunological markers(Baseline, Week 24 During Intervention, and 24,52 Weeks After Intervention)
研究者
Yong Gu
Deputy Director of Endocrinology Dept.; Associate Chief Physician; Associate Professor; Principal Investigator, The First Affiliated Hospital with Nanjing Medical University
Nanjing Medical University