Observational Study of Glucose Tolerance Abnormalities in Patient With Cystic Fibrosis Homozygous for Phe 508 Del CFTR Treated by Lumacaftor-Ivacaftor
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 55
- 试验地点
- 13
- 主要终点
- Measure of 2 hours plasma glucose value (mmol/l) of OGTT, change from baseline at one year of Lumacaftor-Ivacaftor treatment
研究概览
简要总结
Cystic Fibrosis related diabetes (CFRD), a major factor of morbid-mortality in CF, is characterized by a preclinical phase of glucose intolerance particularly long reaching up to 10 years.
At the physiopathology level, insulin secretion is determinant in the glucose tolerance abnormalities in CF. Indeed insulin secretion is dependent of the CFTR activity at the beta cell surface and inhibition of CFTR leads to a decrease in insulin secretion.
Recently, the combination of the lumacaftor, a CFTR corrector, with Ivacaftor, a CFTR potentiator, was studied in patient with CF homozygous for the Phe508 del CFTR mutation patients and showed an improvement of the respiratory state in comparison with the placebo group.
These data suggests that lumacaftor in combination with ivacaftor in targeting CFTR action may have an early impact on the insulin-secretion and consequently on the glucose tolerance.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patients with CF homozygous for the Phe508del CFTR mutation aged 12 years and over
- •Combined Lumacaftor-Ivacaftor treatment scheduled or already started
- •glucose intolerance in OGTT (ADA criteria) or newly diabetes diagnosed at the OGTT (ADA criteria) or diabetic patients with insulin requirement ≤ 0.3 unit / kg / day or without insulin treatment
- •signed informed consent of patient and of one parent OR legal representative for minor subject
排除标准
- •hypersensitivity to the active substances or to any of the excipients of Lumactfor -Ivacaftor
- •lung and/or liver transplant patient
- •Known diabetes with insulin treatment > 0.3 unit / kg / day
- •patient pregnant or wishing to pregnancy
研究组 & 干预措施
Patient
Patient with cystic fibrosis homozygous for Phe 508 del CFTR having a glucose intolerance or newly diagnosis diabetes
干预措施: Lumacaftor-Ivacaftor treatment (Drug)
结局指标
主要结局
Measure of 2 hours plasma glucose value (mmol/l) of OGTT, change from baseline at one year of Lumacaftor-Ivacaftor treatment
时间窗: Day 0 (traitement beginning) and year 1
次要结局
- HOMA -R , HOMA-S(Day 0 (traitement beginning) and year 1)
- (BMI) body mass index(Day 0 (traitement beginning) and year 1)
- Weight (Kg) maximum weight never reached(Day 0 (traitement beginning) and year 1)
- Fasting and one hour glucose value of OGTT (mmol/l)(Day 0 (traitement beginning) and year 1)
- Duration in hypoglycemic area [hypo CGM = 2 consecutive values below 3.3 mmol/l - % of time spent](Day 0 (traitement beginning) and year 1)
- Variability glycemic indexes: MAGE (mg/dl), SD (mg/dl)(Day 0 (traitement beginning) and year 1)
- Daily insulin doses (UI/day)(Day 0 (traitement beginning) and year 1)
- Mean glucose value per day and 2 h after meal (mg/dl)(Day 0 (traitement beginning) and year 1)
- Duration in hyperglycemic area [for glucose value higher than 7.7 mmol/l, % time /24h](Day 0 (traitement beginning) and year 1)
- HbA1c (mmol/l and %)(Day 0 (traitement beginning) and year 1)
- Number of cures of antibiotics IV and per os /year and interval between 2 cures (week)(Day 0 (traitement beginning) and year 1)
- C peptide and insulin values at T0, 1 , 2 hours of OGTT (µg/l)(Day 0 (traitement beginning) and year 1)
- Albumin and Pre albumin (g/l)(Day 0 (traitement beginning) and year 1)
- O2 saturation (%)(Day 0 (traitement beginning) and year 1)
- Glucose, insulin and C peptide AUC of OGTT (µU/L)(Day 0 (traitement beginning) and year 1)
- Number hypoglycaemic events (below 3.3mmol/L, from midnight to 6 am)(Day 0 (traitement beginning) and year 1)
- FEV1, Vital Capacity (VC) (L and %)(Day 0 (traitement beginning) and year 1)