MATIN-2: Sequential Immune Modulation and Antigen-Specific Tolerance Induction for Disease Modification in Recent-Onset Type 1 Diabetes - A Mechanistic Framework and Phase I/II Protocol Proposal
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 试验地点
- 1
研究概览
简要总结
This study tests a three-phase immune treatment for people recently diagnosed with Type 1 diabetes (within 6 months, with some insulin production remaining).
Phase 1 (weeks 1-2): Teplizumab, an anti-CD3 antibody, is given by infusion to slow immune attack on insulin-producing beta cells.
Phase 2 (months 2-9): Insulin is injected directly into a lymph node (intralymphatic immunotherapy, ILIT) alongside low-dose interleukin-2 to teach the immune system to tolerate insulin and expand protective regulatory T cells.
Phase 3 (months 10-24): Low-dose interleukin-2 is continued to maintain immune tolerance.
The main goal is to preserve the body's remaining insulin production (measured by C-peptide). Sixty adults aged 18-45 will be randomly assigned to the MATIN-2 protocol or standard care. Safety, immune markers, and HbA1c will also be monitored.
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
- Single (Outcomes Assessor)
盲法说明
Outcomes assessors performing laboratory analyses (C-peptide, HbA1c, immune markers) will be blinded to treatment allocation. Participants and care providers will not be blinded due to the nature of the interventions.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-45 years
- •Clinical diagnosis of Type 1 diabetes mellitus within 6 months of enrolment
- •Positive for at least one diabetes-related autoantibody (GAD65, IA-2, ZnT8, or IAA)
- •Detectable fasting or stimulated C-peptide ≥ 0.2 nmol/L
- •HbA1c ≤ 10% (86 mmol/mol)
- •Ability to provide written informed consent
排除标准
- •Prior immunosuppressive therapy within 3 months
- •Active or chronic infection (HIV, hepatitis B/C, tuberculosis)
- •Current or prior malignancy within 5 years (except non-melanoma skin cancer)
- •Pregnancy or breastfeeding
- •Severe renal impairment (eGFR < 30 mL/min/1.73m²)
- •Severe hepatic impairment (Child-Pugh C)
- •Known hypersensitivity to teplizumab or any excipient
- •Participation in another interventional trial within 30 days
- •Current systemic corticosteroid or immunomodulatory agent use
- •History of other autoimmune disease requiring immunosuppression
- •Absolute lymphocyte count < 1.0 × 10⁹/L
- •ALT or AST > 3× upper limit of normal
- •Haemoglobin < 100 g/L
- •Unwillingness to use contraception during study period
研究者
Abdullah Kars
Lieutenant Colonel, Kara Harp Okulu (Turkish Military Academy)
Kara Harp Okulu (Turkish Military Academy)