EnVision CF Multicenter Study of Glucose Tolerance in Cystic Fibrosis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 317
- 试验地点
- 8
- 主要终点
- age- and sex-based nomograms for OGIS (oral glucose insulin sensitivity)
研究概览
简要总结
Cystic Fibrosis Related Diabetes has been identified by the CF community as one of the top ten priorities for CF research. In CF clinical decline due to dysglycemia begins early, prior to diagnosis of diabetes and increases mortality from pulmonary disease. There is presently no way to determine who, of those with dysglycemia, will experience clinical compromise. However, the CF Center in Milan has found that measurable age- and sex-dependent variables on oral glucose tolerance testing (OGTT) predict β-cell failure-the primary driver of decline in CF. the investigators propose a multi-center trial to develop nomograms of age and sex dependent reference values for OGTT-derived measures including glucose, insulin, c-peptide, and the resultant OGTT-derived estimates of β-cell function, β cell sensitivity to glucose, and oral glucose insulin sensitivity (OGIS) and to determine correlation of these with clinical status (FEV-1, BMI z score, number of pulmonary exacerbations over the past 12 months). In a subset of the cohort the investigators will perform additional studies to determine possible mechanisms driving abnormal β cell function, including the role of lean body mass (as measured by DXA), impact of incretin (GLP-1, GIP) and islet hormones (glucagon, pancreatic polypeptide) on β cell function and the relationship of reactive hypoglycemia and catecholamine responses to β cell function, as well as the relationship of β cell sensitivity to glucose as determined by our model to abnormalities in blood glucose found in a period of free living after the study (determined by continuous glucose monitoring measures (Peak glucose, time spent >200 mg/dl, standard deviation). the investigators will also develop a biobank of stored samples to allow expansion to the full cohort if warranted and to enable future studies of dysglycemia and diabetes in CF. the investigator's eventual goal is utilization of the nomograms to determine the minimum number of measures to accurately predict risk for clinical decline from dysglycemia in CF.
详细描述
A. Hypotheses and Specific Aims:
Cystic Fibrosis Related Diabetes Mellitus (CFRD) has been identified by the CF community as one of the top ten priorities for CF research1. In CF, clinical decline due to dysglycemia begins early, prior to the diagnosis of CFRD2 and increases pulmonary decline and mortality3. However, current definitions of dysglycemia were derived from non-CF populations, and unfortunately, there is presently no way to determine who, of those with CF and dysglycemia, will experience morbidity, mortality or greatest risk for CFRD. However, the CF Center in Milan found that measurable age and sex dependent variables on oral glucose tolerance testing (OGTT) strongly predict β-cell failure 4- the primary driver of clinical decline. We propose a multi-center trial to determine age and sex dependent reference for fsOGTT-derived estimates of β-cell function and insulin sensitivity in the US CF population, and to investigate the relationship of these measures to CF-relevant clinical outcomes as well as exploring potential mechanisms that may be driving beta cell functional decline. Furthermore, we will collect these data in the new age of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, to define a model that will be most relevant for our current generation of CF patients.
Specific Aim 1: To determine age and sex dependent reference values from OGTT and OGTT-derived estimates of β-cell function and insulin sensitivity in a diverse population of 475 non-diabetic children and adults with CF, at 4 centers with EnVision Emerging Leaders as site-PIs.
Hypothesis: Much like standard growth charts with means and standard-deviation based percentiles, fsOGTT values (glucose, insulin, c-peptide) and the resultant fsOGTT-derived estimates of β-cell function (beta cell sensitivity to glucose, oral glucose insulin sensitivity) will fall along an age and sex-dependent continuum which will be consistent across CF patients at four different US centers.
Specific Aim 2: To determine the relationship between OGTT reference values and estimates of β-cell function and insulin sensitivity to clinically relevant outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >/= 6 years
- •Diagnosis of cystic fibrosis
- •CF patients regularly attending the CF centers
- •Clinically stable in previous 3wks:
- •absence of major clinical events including pulmonary exacerbations,
- •no change in their habitual treatment regimen including introduction of antibiotics or steroids in the past 3 weeks
排除标准
- •Diagnosis of type 1 diabetes, type 2 diabetes, or MODY
- •Organ transplantation
- •new diagnosis of CFRD in the past 6 months
- •antidiabetic treatment in past 6 mos (insulin or oral hypoglycemic agents)
- •patients with previous CFRD diagnosis, but not currently taking insulin/glucose-lowering medications for at least 6 months should be included
- •pulmonary exacerbation associated with systemic steroid requirement in the last 6 months
- •on CFTR corrector less than 6 months prior to enrollment
结局指标
主要结局
age- and sex-based nomograms for OGIS (oral glucose insulin sensitivity)
时间窗: the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months
The primary outcome of this study is to establish age- and sex-based nomograms ("growth charts") ranging from the 5th-95th % for OGIS (oral glucose insulin sensitivity)
age- and sex-based nomograms for beta cell glucose sensitivity
时间窗: the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months
The primary endpoint is relationship of beta cell sensitivity to glucose to age. To assess the primary endpoint, the following method will be used: Quantiles of beta-cell glucose sensitivity will be calculated using quantile regression. The outcome variable of the quantile curve is beta-cell glucose sensitivity (continuous, picomol per minute-1 per meter-2 per millimole-1) and the predictor variable is age (continuous, years). On the basis of the available data, we expect a linear relationship between beta-cell glucose sensitivity and age with no heteroskedasticy
次要结局
- evaluate the relationships between age and sex-based quantiles for beta cell glucose sensitivity and FEV-1(the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months)
- evaluate the relationships between age and sex-based quantiles for OGIS and FEV-1(the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months)
- evaluate the relationships between age and sex-based quantiles for beta cell glucose sensitivity and BMI Z-score(data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months)
- evaluate the relationships between age and sex-based quantiles for insulin and BMI z-score(the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months)
- evaluate the relationships between age and sex-based quantiles for c-peptide and FEV-1(the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months)
- evaluate the relationships between age and sex-based quantiles for OGIS and BMI z-score(the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months)
- evaluate the relationships between age and sex-based quantiles for insulin and FEV-1(the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months)
- evaluate the relationships between age and sex-based quantiles for beta cell glucose sensitivity and pulmonary exacerbations in the previous 12 months(the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months)
- evaluate the relationships between age and sex-based quantiles for c-peptide and number of pulmonary exacerbations in the previous 12 months(the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months)
- evaluate the relationships between age and sex-based quantiles for OGIS and the number of pulmonary exacerbations in the previous 12 months(the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months)
- evaluate the relationships between age and sex-based quantiles for insulin and number of pulmonary exacerbations in the previous 12 months(the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months)
- evaluate the relationships between age and sex-based quantiles for c-peptide and BMI z-score(the data will be gathered at the study visit (one visit of 4+ per year over the 3 years of the study)-data analysis will occur at study close (approximately 2.5 to 3 years from the start of enrollment) data analysis and modeling will take 1-2 months)
研究者
Katie Larson Ode
Clinical Associate Professor Pediatric Endocrinology & Diabetes
University of Iowa