Predicting Development of Diabetes Mellitus in Patients Undergoing Allogeneic Stem Cell Transplant
2019년 7월 15일 업데이트: Brian Engelhardt, MD, Vanderbilt-Ingram Cancer Center
Metabolic and CD4+ T Cell Dysregulation in Post-Transplant Diabetes Mellitus
This clinical trial studies the physiology and immunology of new-onset post-transplant diabetes mellitus in patients undergoing allogeneic stem cell transplantation.
Oral glucose tolerance testing (OGTT), euglycemic hyperinsulinemic 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.
연구 개요
상태
종료됨
상세 설명
PRIMARY OBJECTIVES:
I. To determine whether pre-transplant insulin resistance predicts for the development of new onset post-transplant diabetes mellitus (PTDM) in individuals without diabetes undergoing matched related donor (MRD) hematopoietic stem cell transplant (HCT).
II. To define the role of circulating tissue-specific Th1 cells in the development of PTDM.
III. To characterize the phenotype and function of circulating tissue-specific regulatory T cells (Tregs) in HCT recipients with or without PTDM.
OUTLINE:
Patients undergo OGTT and a standard 2-step euglycemic hyperinsulinemic clamp procedure prior to HCT. Patients then undergo repeat OGTT and a 2-step euglycemic hyperinsulinemic clamp procedure once after HCT between days 90-100.
연구 유형
중재적
등록 (실제)
22
단계
- 해당 없음
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
-
-
Tennessee
-
Nashville, Tennessee, 미국, 37232
- Vanderbilt-Ingram Cancer Center
-
-
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- Patients undergoing MRD allogeneic HCT
- DONOR: Donors undergoing stem cell collection for match related allogeneic stem cell transplant
Exclusion Criteria:
- Patients who have not received an allogeneic HCT
- Recent or current history of diabetes mellitus, defined as:1) diabetes therapy within 6 months of enrollment, or 2) fasting blood glucose at "pre-admit" (screening) visit >= 126 mg/dL
- Pregnancy or breastfeeding
- Unrelated donor, umbilical cord blood, mismatched, or haploidentical transplants
- Patients receiving T cell depletion or thymoglobulin as part of their transplant
- Patients on established, chronic corticosteroid therapy (> 5 mg /day of prednisone or prednisone equivalent) prior to transplant; established, chronic corticosteroid therapy is defined as daily dosing of > 5 mg/day of prednisone or prednisone equivalent for at least 2 weeks prior to the start of conditioning/chemotherapy or plans to continue pre-transplant corticosteroids (> 5 mg/day of prednisone or prednisone equivalent) indefinitely after transplantation
- Inability to give informed consent
- Any condition which, in the opinion of the investigator, might interfere with study objective
- Any reason which, in the opinion of the investigator, adds additional risk to the patient
- DONOR: Individuals not donating stem cells
- DONOR: Pregnancy or breastfeeding
- DONOR: Inability to give informed consent
- DONOR: Any condition which, in the opinion of the investigator, might interfere with study objective
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 지지 요법
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: Diagnostic (OGTT, euglycemic hyperinsulinemic clamp)
Patients undergo OGTT and a standard 2-step euglycemic hyperinsulinemic clamp procedure prior to HCT.
Patients then undergo repeat OGTT and a 2-step euglycemic hyperinsulinemic clamp procedure once after HCT between days 90-100.
|
상관 연구
During OGTT 75gm of glucose will be given followed by phlebotomy
During clamp procedure tritiated glucose, D20, regular insulin will be given, followed by phlebotomy.
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Pre-transplant peripheral insulin sensitivity and glucose disposal as defined by the peripheral insulin sensitivity index among patients who do or do not go on to develop PTDM
기간: Up to 21 days pre-transplant
|
Patients will be followed for 100 days after transplant for development of diabetes.
Wilcoxon rank sum test will be applied to compare the population mean difference between these two groups.
Multivariable logistic regression will evaluate whether the peripheral insulin sensitivity index is an independent predictor of PTDM after adjusting for the following covariates: fasting C-peptide level, 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.
|
Up to 21 days pre-transplant
|
|
Ratio of circulating, gut-homing (alpha4beta7+) Th1 subsets pre-transplant with the development of PTDM after HCT
기간: Up to day 100 after transplant
|
Wilcoxon rank sum test will be applied to compare the mean difference between these two groups.
|
Up to day 100 after transplant
|
|
Expression of Helios or glycoprotein A repetitions predominant in alpha4beta7+Foxp3+ Tregs versus alpha4beta7+Foxp3- conventional T cells
기간: Up to day 100 after transplant
|
Wilcoxon rank sum test or two-sample t-test will be applied to compare the mean difference between two groups.
Data will be presented using means and standard deviations for continuous variables, as well as percentage and frequency for categorical variables.
|
Up to day 100 after transplant
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Changes in hepatic insulin sensitivity among patients with or without established PTDM
기간: Baseline to day 90 after transplant
|
Comparison between two independent groups, e.g., with or without PTDM, will be carried out using either two-sample t-test or Wilcoxon rank sum test for continuous variables and Chi-square test or Fisher's exact test for categorical variables.
|
Baseline to day 90 after transplant
|
|
Changes in peripheral insulin sensitivity among patients with or without established PTDM
기간: Baseline to day 90 after transplant
|
Comparison between two independent groups, e.g., with or without PTDM, will be carried out using either two-sample t-test or Wilcoxon rank sum test for continuous variables and Chi-square test or Fisher's exact test for categorical variables.
|
Baseline to day 90 after transplant
|
|
Changes in OGTT results among patients with or without established PTDM
기간: Baseline to day 90 after transplant
|
Comparison between two independent groups, e.g., with or without PTDM, will be carried out using either two-sample t-test or Wilcoxon rank sum test for continuous variables and Chi-square test or Fisher's exact test for categorical variables.
|
Baseline to day 90 after transplant
|
|
Changes in hepatic insulin sensitivity in the entire cohort
기간: Baseline to day 90 after transplant
|
For the comparison of the changes between baseline and day+90 after transplant in the entire cohort, the mean difference will be compared with paired Student's t-test or Wilcoxon signed rank test for continuous variables and a McNemar's test for categorical variables.
|
Baseline to day 90 after transplant
|
|
Changes in peripheral insulin sensitivity in the entire cohort
기간: Baseline to day 90 after transplant
|
For the comparison of the changes between baseline and day+90 after transplant in the entire cohort, the mean difference will be compared with paired Student's t-test or Wilcoxon signed rank test for continuous variables and a McNemar's test for categorical variables.
|
Baseline to day 90 after transplant
|
|
Changes in OGTT results among patients in the entire cohort
기간: Baseline to day 90 after transplant
|
For the comparison of the changes between baseline and day+90 after transplant in the entire cohort, the mean difference will be compared with paired Student's t-test or Wilcoxon signed rank test for continuous variables and a McNemar's test for categorical variables.
|
Baseline to day 90 after transplant
|
|
Changes in hepatic insulin sensitivity among different groups
기간: Baseline to day 90 after transplant
|
To compare the differences between baseline (pre-transplant) and day +90 test results among various groups, linear mixed model will be applied to continuous outcomes (i.e., peripheral insulin sensitivity and hepatic glucose production) and generalized linear mixed model to noncontinuous outcomes (i.e., OGTT results).
Groups of interest will be created by stratifying patients based on PTDM, conditioning regimen (ablative vs. reduced intensity) or acute GVHD treated with steroids.
|
Baseline to day 90 after transplant
|
|
Changes in peripheral insulin sensitivity among different groups
기간: Baseline to day 90 after transplant
|
To compare the differences between baseline (pre-transplant) and day +90 test results among various groups, linear mixed model will be applied to continuous outcomes (i.e., peripheral insulin sensitivity and hepatic glucose production) and generalized linear mixed model to noncontinuous outcomes (i.e., OGTT results).
Groups of interest will be created by stratifying patients based on PTDM, conditioning regimen (ablative vs. reduced intensity) or acute GVHD treated with steroids.
|
Baseline to day 90 after transplant
|
|
Changes in OGTT results among different groups
기간: Baseline to day 90 after transplant
|
To compare the differences between baseline (pre-transplant) and day +90 test results among various groups, linear mixed model will be applied to continuous outcomes (i.e., peripheral insulin sensitivity and hepatic glucose production) and generalized linear mixed model to noncontinuous outcomes (i.e., OGTT results).
Groups of interest will be created by stratifying patients based on PTDM, conditioning regimen (ablative vs. reduced intensity) or acute GVHD treated with steroids.
|
Baseline to day 90 after transplant
|
|
Ability of pre-transplant or post-transplant tissue-specific Tregs or Th1 cells to predict the development of PTDM
기간: Up to day 100 after transplant
|
The comparison between independent groups, e.g., with or without PTDM or the three OGTT groups (normal, impaired glucose tolerance, or diabetic), will be carried out using either Wilcoxon rank sum test or Kruskal-Wallis test, respectively.
|
Up to day 100 after transplant
|
|
Insulin clamp indices
기간: Up to day 100 after transplant
|
Spearman correlation will be used to evaluate the correlation between insulin clamp indices and Th1/Treg frequencies.
|
Up to day 100 after transplant
|
|
Th1/Treg frequencies
기간: Up to day 100 after transplant
|
Spearman correlation will be used to evaluate the correlation between insulin clamp indices and Th1/Treg frequencies.
|
Up to day 100 after transplant
|
|
Pre-HCT Th1 and Treg tissue-specific subsets
기간: Up to 100 days pre-transplant
|
Spearman correlation will evaluate the association between pre-HCT Th1 and Treg tissue-specific subsets with post-HCT donor derived Th1 and Treg.
|
Up to 100 days pre-transplant
|
|
Ability of alpha4beta7+ Tregs from patients with or without PTDM in suppressing the proliferation of allogeneic T cells
기간: Up to day 90 after transplant
|
Wilcoxon rank sum test or two-sample t-test will be applied to compare the mean difference between two groups.
Data will be presented using means and standard deviations for continuous variables, as well as percentage and frequency for categorical variables.
Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity will be made for the parametric test such as t-test and mixed model.
If necessary, data will be transformed utilizing appropriate transformations such as the log or square root.
|
Up to day 90 after transplant
|
|
Ability of effector T cells from patients with PTDM to be resistant to suppression from Tregs obtained from healthy individuals
기간: Up to day 100 after transplant
|
Wilcoxon rank sum test or two-sample t-test will be applied to compare the mean difference between two groups.
Data will be presented using means and standard deviations for continuous variables, as well as percentage and frequency for categorical variables.
|
Up to day 100 after transplant
|
|
Post-HCT donor derived Th1 and Treg subsets
기간: Up to 100 days pre-transplant
|
Spearman correlation will evaluate the association between pre-HCT Th1 and Treg tissue-specific subsets with post-HCT donor derived Th1 and Treg.
|
Up to 100 days pre-transplant
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
- 수석 연구원: Brian Engelhardt, Vanderbilt-Ingram Cancer Center
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2014년 11월 20일
기본 완료 (실제)
2019년 1월 8일
연구 완료 (실제)
2019년 1월 8일
연구 등록 날짜
최초 제출
2014년 8월 28일
QC 기준을 충족하는 최초 제출
2014년 9월 11일
처음 게시됨 (추정)
2014년 9월 15일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2019년 7월 18일
QC 기준을 충족하는 마지막 업데이트 제출
2019년 7월 15일
마지막으로 확인됨
2019년 7월 1일
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
진성 당뇨병에 대한 임상 시험
-
Fondazione Policlinico Universitario Agostino Gemelli...아직 모집하지 않음비만 | 제2형 당뇨병 | 인슐린 저항성 당뇨병 (Mellitus)
실험실 바이오마커 분석에 대한 임상 시험
-
ORIOL BESTARD완전한신장 이식 | CMV 감염스페인, 벨기에
-
Central and North West London NHS Foundation TrustBritish HIV Association (BHIVA)아직 모집하지 않음
-
Hvidovre University HospitalElsassFonden종료됨
-
Seoul National University Bundang Hospital완전한
-
Spaarne GasthuisLeiden University Medical Center모집하지 않고 적극적으로
-
Rio de Janeiro State UniversityCoordenação de Aperfeiçoamento de Pessoal de Nível Superior.; Conselho Nacional de Desenvolvimento... 그리고 다른 협력자들완전한