Islet Cell and ST2 Axis Dysregulation in Post-Transplant Diabetes Mellitus
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Pre-transplant insulin secretion will be measured as glucose stimulated insulin secretion (GSIS) during a hyperglycemic clamp procedure among patients who do or do not go on to develop PTDM (univariable analysis).
研究概览
简要总结
This clinical research studies the physiology and immunology of new-onset post-transplant diabetes mellitus in patients undergoing allogeneic stem cell transplantation. Oral glucose tolerance tests (OGTT), hyperglycemic clamps, and immune assays will be used to define the mechanisms associated with abnormal glucose homeostasis following stem cell transplantation. Information from this clinical trial could be used to develop standardized screening procedures or to develop optimal treatment strategies for patients developing post-transplant diabetes mellitus.
详细描述
PRIMARY OBJECTIVES:
I. To determine if changes in islet cell physiology are detectable before or after matched related donor (MRD) hematopoietic stem cell transplant (HCT) in patients developing new-onset post-transplant diabetes mellitus (PTDM).
- To determine if a compensatory increase in glucose stimulated insulin secretion (GSIS) by β-cells precedes PTDM development in patients without diabetes undergoing MRD HCT.
- To determine if excess glucagon secretion and impaired α-cell response to glucose or GLP-1 contributes to the hyperglycemia of PTDM.
II. To determine if the IL-33/ST2 axis promotes immune/islet cell dysregulation during PTDM.
OUTLINE:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 1 for MRD HCT Recipients
Patients undergo an Oral Glucose Tolerance Test (OGTT) and 1 hyperglycemic clamp will be performed on separate days prior to transplant and then each procedure will be repeated once between day+80 to day+100 (+/- 10 days) after transplant.
干预措施: Oral Glucose Tolerance Test (OGTT) (Drug)
Arm 1 for MRD HCT Recipients
Patients undergo an Oral Glucose Tolerance Test (OGTT) and 1 hyperglycemic clamp will be performed on separate days prior to transplant and then each procedure will be repeated once between day+80 to day+100 (+/- 10 days) after transplant.
干预措施: Hyperglycemic clamp procedure (Drug)
Arm 2 for MRD HCT Recipients
Patients undergo 2 Oral Glucose Tolerance Test (OGTTs) (with and without GLP-1 analogue) will be performed on separate days prior to transplant and then each procedure will be repeated once between day+80 to day+100 (+/- 10 days) after transplant.
干预措施: 2 OGTTs with and without GLP-1 analogue (Drug)
结局指标
主要结局
Pre-transplant insulin secretion will be measured as glucose stimulated insulin secretion (GSIS) during a hyperglycemic clamp procedure among patients who do or do not go on to develop PTDM (univariable analysis).
时间窗: Up to 28 days pre-transplant
A hyperglycemic clamp procedure will be performed pre-transplant. Pre-transplant will be defined as no more than 28 days before allogeneic hematopoietic cell transplantation. Patients will then be followed for 100 days after transplant for development of diabetes. In univariable analysis, a Wilcoxon rank sum test will be applied to compare the population mean difference in GSIS between these two groups.
Post-transplant glucagon secretion will be measured during the oral glucose tolerance test among patients who do or do not develop PTDM (univariable analysis).
时间窗: Up to 100 days after transplant
Patients will be followed for 100 days after transplant for development of diabetes. In univariable analysis, a Wilcoxon rank sum test will be applied to compare the population mean difference in glucagon secretion between these two groups.
Plasma IL-33 levels will be measured among patients who do or do not develop PTDM (multivariable analysis).
时间窗: Up to 100 days after transplant
In multivariable analysis, logistic regression will evaluate whether IL-33 is independently associated with PTDM after adjusting for the following covariates: gender, conditioning (ablative vs. reduced intensity), or acute graft-versus-host disease (GVHD) requiring steroids. The estimated odds ratio (OR) and 95% confidence interval of the OR will be provided to measure the effect of the association.
Pre-transplant insulin secretion will be measured as glucose stimulated insulin secretion (GSIS) during a hyperglycemic clamp procedure among patients who do or do not go on to develop PTDM (multivariable analysis).
时间窗: Up to 28 days pre-transplant
A hyperglycemic clamp procedure will be performed pre-transplant. Pre-transplant will be defined as no more than 28 days before allogeneic hematopoietic cell transplantation. Patients will then be followed for 100 days after transplant for development of diabetes. In multivariable analysis, logistic regression will evaluate whether GSIS is an independent predictor of PTDM after adjusting for the following covariates: gender, conditioning (ablative vs. reduced intensity), or acute graft-versus-host disease (GVHD) requiring steroids. The estimated odds ratio (OR) and 95% confidence interval of the OR will be provided to measure the effect of the association.
Post-transplant glucagon secretion will be measured during the oral glucose tolerance test among patients who do or do not develop PTDM (multivariable analysis).
时间窗: Up to 100 days after transplant
Patients will be followed for 100 days after transplant for development of diabetes. In multivariable analysis, a logistic regression will evaluate whether glucagon secretion is independently associated with PTDM after adjusting for the following covariates: gender, conditioning (ablative vs. reduced intensity), or acute graft-versus-host disease (GVHD) requiring steroids. The estimated odds ratio (OR) and 95% confidence interval of the OR will be provided to measure the effect of the association.
Plasma IL-33 levels will be measured among patients who do or do not develop PTDM (univariable analysis).
时间窗: Up to 100 days after transplant
Patients will be followed for 100 days after transplant for development of diabetes. In univariable analysis, a Wilcoxon rank sum test will be applied to compare the population mean difference in IL-33 between these two groups.
次要结局
未报告次要终点
研究者
Brian Engelhardt, MD
Associate Professor of Medicine
Vanderbilt-Ingram Cancer Center