Autologous Adoptive T Regulatory Cell Transfer in Autoimmune Diseases: Anon-randomized Open Label Phase 1 Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Safety of the adoptive T regs transfer
研究概览
简要总结
Investigators aim to develop an effective and safe treatment of autoimmune diseases through adoptive T regulatory cells transfer. Our objectives are to evaluate the safety and efficacy of autologous adoptive Treg (CD4CD25FoxP3 CD127 low regulatory) cell transfer to patients with refractory autoimmune diseases: Refractory lupus Nephritis, and adults' type1 diabetes mellitus. Patients and Methods: This is Non randomized open label phase 1 pilot study including ten patients with refractory lupus nephritis and ten patients with Type 1 diabetic patients. All patients will be subjected to Full history taking, clinical examination and pretreatment investigations according to the type of autoimmune disease then regulatory T cells (Tregs) identification and count, Treg isolation and expansion and finally administration of T reg cells and follow-up of adverse events and outcomes.
详细描述
Autoimmune disorders are chronic diseases caused by the breakdown of tolerance against self-antigens
; one hypothesis involves a failure in central and peripheral tolerance with the latter being associated with reduced Treg (CD4+CD25+FpxP3CD127- T- Regulatory )cells number or failure in their function (6).
In preclinical studies, human CD4+CD25+CD127- Treg cells have been shown to be effective in preventing Graft vs. Host Disease (GvHD) (7, 23), autoimmune diseases (13,22) and delaying graft rejection (19, 26).
The positive outcomes gave the rationale to apply Treg cells for the treatment of human diseases and results from the first clinical trials with adoptively transferred Treg cells investigators published in 2009 (24).
What does this study add? This is the first interventional study on adoptive Treg cell transfer in Egypt as a therapeutic trial for patients with refractory autoimmune diseases who do not respond to base line of care treatment available in the institute. Separation of this Treg cells was done in Egyptian patients but as a descriptive study only (as mentioned below).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed as refractory lupus nephritis .
- •Hemoglobin level> or equal 11g/dl before withdrawal of blood from patient to isolate T reg cells.
- •Written informed consent from every patient before participation.
排除标准
- •Diabetes mellitus
- •End-stage renal disease.
- •Pregnant and lactation.
- •Patients on treatment by high-dose glucocorticoids more than 20 mg/day at the time of enrollment.
- •Patients having psychiatric or neurological disease interfere with getting informed consent.
- •Patients having fever, local or systemic infection at time of administration of adoptive T reg cells.
- •Age less than or equal 18 years old.
- •Patients with other autoimmune disease.
- •Vitamin D deficient patients
- •Group 2: type 1 diabetes Meletus
- •Inclusion criteria:
- •Documented Autoimmune type 1 diabetes Meletus (TID) with disease duration ≤ 1 year, Anti GAD antibodies will be measured to all recruited patients to document autoimmunity.
- •Age ≥ 18 years old.
- •Fasting plasma C-peptide levels >0.4 ng/mL.
- •Patients on basal-bolus therapy
- •HbA1c % ≤ 8%
- •Hemoglobin level> or equal 11g/dl before withdrawal of blood from patient to isolate T reg cells.
- •Written informed consent from every patient before participation.
- •Exclusion criteria:
- •Patients having, fever, local or systemic infection at time of infusion of adoptive T reg cells.
- •Patient having coronary heart disease
- •End-stage renal disease
- •Pregnant and lactating patients
- •Patients having psychiatric or neurological disease interfere with getting informed consent.
- •Patients having other autoimmune disease other than TID.
- •Vitamin D deficient Patients.
结局指标
主要结局
Safety of the adoptive T regs transfer
时间窗: 4 weeks
percentage of patients who developed toxic adverse events
Efficacy of the adoptive T regs transfer
时间窗: 44 weeks
Serum detection of INF-gama,TNF-alpha,IL1,IL2,TGF-beta,IL-10,IL-17
次要结局
- Prevention or stop progression to organ failure(44 weeks)
研究者
zeinab ahmed yousif hasan ashour
professor of internal medicine, allergy and clinical immunology
Ain Shams University