Prevention of Clinical Onset of Type 1 Diabetes by Daily Administration of Metabolically Active Insulin in High Risk First Degree Relatives.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 112
- 试验地点
- 3
- 主要终点
- Fasting glycemia;
研究概览
简要总结
Prophylactic administration of metabolically active insulin can prevent or delay clinical onset of diabetes in a high risk group of nondiabetic siblings as defined by positivity for autoantibodies against IA-2 (IA-2-A).
详细描述
Hypotheses:
Primary: Prophylactic administration of metabolically active insulin can prevent or delay clinical onset of diabetes in a high risk group of nondiabetic siblings as defined by positivity for autoantibodies against IA-2 (IA-2-A).
Secondary: 1) Untreated siblings with positivity for IA-2-A develop clinical diabetes significantly faster than untreated offspring with the same marker positivity. 2) Plasma proinsulin levels increase disproportionately before clinical onset of Type 1 diabetes both in siblings and offspring. 3) Prophylactic administration of metabolically active insulin reduces the plasma proinsulin/C-peptide ratio in non-diabetic antibody positive siblings and offspring. 4) Prophylactic administration of metabolically active insulin reduces the presence and/or levels of diabetes-associated autoantibodies directed against islet cell components.
Endpoints: Fasting glycemia; fasting and stimulated plasma C-peptide and proinsulin values; islet cell autoantibodies; incidence of hypoglycemia; body weight gain.
研究设计
- 研究类型
- Interventional
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 39 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Sibling/offspring of a Type 1 diabetic patient
- •in good general condition
- •age 5-39 years
- •fasting plasma glucose <126 mg/dL AND an OGTT that is non-diabetic by 1997 ADA criteria (33):
- •Normal glycemia:
- •fasting plasma glucose < 110 mg/dL and
- •2 hour plasma glucose < 140 mg/dL
- •Impaired Fasting Glucose (IFG):
- •fasting plasma glucose 110-125 mg/dL and
- •2 hour plasma glucose < 140 mg/dL
- •Impaired Glucose Tolerance (IGT):
- •fasting plasma glucose <110 mg/dL and
- •2 hour plasma glucose 140-199 mg/dL
- •at least positive for IA-2-A
- •absence of a protective DQ genotype: A4-B2/X or X/Y or X/X where X = A2-B3.3, A1-B1.9, A1-B1.2, A4-B3.1, A2-B2 or A4.23-B3.1 Y = A1-B1.1, A1-B2, A1-B1.AZH, A3-B2, A3-B3.1, A3-B3.3, A3-B4, A4-B4, A4.23-B4, A4-B3.2, A3-B1.1, A4-B3.3, A4-B1.1 or A4.23-B2 (32)
- •cooperative and reliable subject (age ≥ 14 yrs) / parents (age < 14 yrs) giving informed consent by signature; the patient/parents should be informed in sufficient detail on the content and procedure of the protocol, indicating potential risks of insulin therapy; early intervention with metabolically active insulin treatment should be identified as a clinical trial. Both parents should sign and agree with the protocol procedure.
排除标准
- •diabetes by 1997 ADA criteria (33):
- •fasting plasma glucose ≥ 126 mg/dL, or
- •2 hour plasma glucose ≥ 200 mg/dL
- •donation of blood during the study or within one month prior to screening
- •pregnancy or lactation in women
- •use of inadequate anticonception by female patients of childbearing potential
- •use of illicit drugs or overconsumption of alcohol (> 3 beers/day) or history of drug or alcohol abuse
- •being legally incapacitated, having significant emotional problems at the time of the study, or having a history of psychiatric disorders
- •having received antidepressant medications during the last 6 months
- •treatment with immune modulating or diabetogenic medication (such as corticosteroids)
- •presently participating in another clinical study or having done so during the last 12 months
- •history of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risks to the patient
研究组 & 干预措施
1
56 subjects will receive metabolically active insulin by subcutaneous injections for 36 months (twice daily)
干预措施: Actrapid HM (Drug)
结局指标
主要结局
Fasting glycemia;
时间窗: 2004
fasting and stimulated plasma C-peptide and proinsulin values;
时间窗: 2004
islet cell autoantibodies;
时间窗: 2004
body weight gain.
时间窗: 2004
次要结局
未报告次要终点