Type 1 Diabetes
Conditions
Keywords
Type 1 Diabetes, Immunotherapy, Pancreatic Beta-Cell Function
Brief summary
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.
Interventions
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).
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).
Sponsors
Nanjing Medical University
The First Affiliated Hospital with Nanjing Medical University
Qilu Pharmaceutical (Hainan) Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects who provide written informed consent. 2. Aged 18-65 years. 3. Diagnosed with Type 1 Diabetes Mellitus (per ADA 2024 criteria). 4. 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. 5. Disease duration ≤100 days post-T1DM diagnosis. 6. Random C-peptide ≥ 200 pmol/L.
Exclusion criteria
1. Pregnancy, lactation, or women of childbearing potential not using contraception. 2. Well-controlled glycemia with oral hypoglycemic agents alone. 3. Participation in other diabetes/immune-modulating trials. 4. ALT/AST \>3× upper limit of normal (ULN). 5. History of malignancy, uncontrolled autoimmune disorders, or active infections. 6. Alcohol/drug abuse, psychiatric disorders, or conditions unsuitable for trial participation. 7. Use of immunosuppressants within 12 weeks prior. 8. Participation in other drug trials within 12 weeks prior. 9. History of drug allergies, hypersensitivity, or drug addiction. 10. Any condition deemed by investigators to compromise study integrity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| Glycemic Control Status | Intervention Week 24, and Post-intervention Weeks 24 and 52 | Hemoglobin A1c (HbA1c) levels and changes from baseline; Number of participants with poor glycemic control (HbA1c \> 9%); Number of participants with good glycemic control (HbA1c \< 6.5%). |
| 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 | — |
| Immunological markers | Baseline, Week 24 During Intervention, and 24,52 Weeks After Intervention | Count, phenotype, and functional characteristics of white blood cell (WBC) subsets (including T cells, B cells, and natural killer \[NK\] cells); serum proinflammatory and regulatory cytokine profiles, along with other immune mediators; and the number of positive types, specific types, and titer levels of islet autoantibodies. |
| 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 Anaphylaxis, Angioedema, and Opportunistic Infections | 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 | — |
| 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 | — |
Countries
China
Contacts
CONTACTYong Gu
Outcome results
None listed