Effect of NPH Insulin, Insulin Detemir and Insulin Glargine on IGFBP-1 Production and Serum IGF-I in Subjects With Type 1 Diabetes Mellitus: An Open-label, Randomised, Triple Cross-over Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- IGF-I(ng/ml)
研究概览
简要总结
The objective is to describe the interaction of equal doses of NPH insulin (Neutral Protamine Hagedorn), insulin Detemir and insulin glargine on IGFBP-1 (Insulin-like Growth Factor Binding Protein-1) production as well as immunoreactive and bioactive IGF-I (Insulin-like Growth Factor-I) after once-daily injection on three separate visits in type 1 diabetic subjects.
详细描述
Because of the importance of receptors activation and potential effects on the IGF system, a head-to-head comparison of the eventual differential impact of intermediate-acting human insulin (NPH), insulin detemir and insulin glargine on the growth hormone-insulin-like growth factor-insulin-like growth factor binding protein (GH-IGF-IGFBP) axis is relevant to be conducted for the safety assurance of insulin analogues. Therefore, this study aims to investigate whether the serum insulin profile obtained by once-daily injection of long-acting insulin analog, insulin detemir or insulin glargine, has a different impact on IGFBPs production and IGF-I concentrations (total IGF-I) bioactivity and tissue-availability as compared to that seen during treatment with intermediate-acting human insulin, NPH insulin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
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
- •Informed consent obtained before any trial-related activities.
- •Diagnosis of diabetes mellitus according to WHO criteria; history and clinical course consistent with type 1 diabetes mellitus.
- •Diagnosed with diabetes for more than 6 years and using continuous subcutaneous insulin infusion (CSII) at least 6 months at time of inclusion.
- •Total daily insulin dose between 0.4 and 1.4 units/kg (both values included)
- •HbA1c between 6% and 9% (both values included).
- •Age ≥ 18 years.
- •BMI between 18.5 and 28 kg /m2 (including both values).
排除标准
- •Known or suspected allergy to trial product(s) or related products.
- •Recurrent major hypoglycaemic episodes.
- •Heart: Unstable Angina Pectoris, AMI < 12 months or heart insufficiency classified according to NYHA III-IV
- •Blood Pressure: Severe uncontrolled hypertension with BP > 180/110 mmHg, sitting
- •Liver: Impaired hepatic function corresponding to serum-ALAT or basic phosphatase > 2 x upper reference limit of the local laboratory.
- •Kidneys: Impaired renal function corresponding to serum-creatinin > 150 μmol/l according to the local laboratory.
- •Any disease judged by the investigator to affect the trial.
- •Pregnancy, breast-feeding or the intention of becoming pregnant or fertile women not using adequate contraceptive measures - adequate contraceptive method is sterilisation, hysterectomy or current use of contraceptive pills or intra uterine device.
研究组 & 干预措施
NPH insulin injection
NPH insulin will be injected in random order in one of three seperated visit days.
干预措施: NPH (Drug)
detemir insulin injection
insulin detemir will be injected in random order in one of three seperated visit days.
干预措施: Detemir (Drug)
glargine insulin injection
insulin glargine will be injected in random order in one of three seperated visit days.
干预措施: Glargine (Drug)
结局指标
主要结局
IGF-I(ng/ml)
时间窗: 16 hours (from 18:00 to 10:00 next day)
Hourly samples will be taken from 18:00 to 10:00 next day.
IGFBP-1(ng/ml)
时间窗: 16 hours (from 18:00 to 10:00 next day)
Hourly samples will be taken from 18:00 to 10:00 next day.
IGFBP-2(ng/ml)
时间窗: 16 hours (from 18:00 to 10:00 next day)
Hourly samples will be taken from 18:00 to 10:00 next day.
IGFBP-3(ng/ml)
时间窗: 16 hours (from 18:00 to 10:00 next day)
Hourly samples will be taken from 18:00 to 10:00 next day.
Growth Hormone(ng/ml)
时间窗: 16 hours (from 18:00 to 10:00 next day)
Hourly samples will be taken from 18:00 to 10:00 next day.
次要结局
- plasma glucose concentration (mmol/L) after a single injection of either NPH insulin, insulin Detemir or insulin glargine(16 hours (from 18:00 to 10:00 next day))
- insulin concentration (mmol/L) after a single injection of either NPH insulin, insulin Detemir or insulin glargine(16 hours (from 18:00 to 10:00 next day))