Predicting Development of Diabetes Mellitus in Patients Undergoing Allogeneic Stem Cell Transplant
15 juillet 2019 mis à jour par: 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.
Aperçu de l'étude
Statut
Résilié
Les conditions
Description détaillée
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.
Type d'étude
Interventionnel
Inscription (Réel)
22
Phase
- N'est pas applicable
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Tennessee
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Nashville, Tennessee, États-Unis, 37232
- Vanderbilt-Ingram Cancer Center
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Soins de soutien
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: 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.
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Études corrélatives
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.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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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
Délai: Up to 21 days pre-transplant
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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.
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Up to 21 days pre-transplant
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Ratio of circulating, gut-homing (alpha4beta7+) Th1 subsets pre-transplant with the development of PTDM after HCT
Délai: Up to day 100 after transplant
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Wilcoxon rank sum test will be applied to compare the mean difference between these two groups.
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Up to day 100 after transplant
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Expression of Helios or glycoprotein A repetitions predominant in alpha4beta7+Foxp3+ Tregs versus alpha4beta7+Foxp3- conventional T cells
Délai: Up to day 100 after transplant
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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.
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Up to day 100 after transplant
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Changes in hepatic insulin sensitivity among patients with or without established PTDM
Délai: Baseline to day 90 after transplant
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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.
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Baseline to day 90 after transplant
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Changes in peripheral insulin sensitivity among patients with or without established PTDM
Délai: Baseline to day 90 after transplant
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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.
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Baseline to day 90 after transplant
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Changes in OGTT results among patients with or without established PTDM
Délai: Baseline to day 90 after transplant
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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.
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Baseline to day 90 after transplant
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Changes in hepatic insulin sensitivity in the entire cohort
Délai: Baseline to day 90 after transplant
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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.
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Baseline to day 90 after transplant
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Changes in peripheral insulin sensitivity in the entire cohort
Délai: Baseline to day 90 after transplant
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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.
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Baseline to day 90 after transplant
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Changes in OGTT results among patients in the entire cohort
Délai: Baseline to day 90 after transplant
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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.
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Baseline to day 90 after transplant
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Changes in hepatic insulin sensitivity among different groups
Délai: Baseline to day 90 after transplant
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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.
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Baseline to day 90 after transplant
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Changes in peripheral insulin sensitivity among different groups
Délai: 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.
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Baseline to day 90 after transplant
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|
Changes in OGTT results among different groups
Délai: 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.
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Baseline to day 90 after transplant
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Ability of pre-transplant or post-transplant tissue-specific Tregs or Th1 cells to predict the development of PTDM
Délai: Up to day 100 after transplant
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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.
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Up to day 100 after transplant
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Insulin clamp indices
Délai: Up to day 100 after transplant
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Spearman correlation will be used to evaluate the correlation between insulin clamp indices and Th1/Treg frequencies.
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Up to day 100 after transplant
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Th1/Treg frequencies
Délai: Up to day 100 after transplant
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Spearman correlation will be used to evaluate the correlation between insulin clamp indices and Th1/Treg frequencies.
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Up to day 100 after transplant
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Pre-HCT Th1 and Treg tissue-specific subsets
Délai: Up to 100 days pre-transplant
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Spearman correlation will evaluate the association between pre-HCT Th1 and Treg tissue-specific subsets with post-HCT donor derived Th1 and Treg.
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Up to 100 days pre-transplant
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Ability of alpha4beta7+ Tregs from patients with or without PTDM in suppressing the proliferation of allogeneic T cells
Délai: Up to day 90 after transplant
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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.
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Up to day 90 after transplant
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Ability of effector T cells from patients with PTDM to be resistant to suppression from Tregs obtained from healthy individuals
Délai: Up to day 100 after transplant
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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.
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Up to day 100 after transplant
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Post-HCT donor derived Th1 and Treg subsets
Délai: Up to 100 days pre-transplant
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Spearman correlation will evaluate the association between pre-HCT Th1 and Treg tissue-specific subsets with post-HCT donor derived Th1 and Treg.
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Up to 100 days pre-transplant
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Brian Engelhardt, Vanderbilt-Ingram Cancer Center
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
20 novembre 2014
Achèvement primaire (Réel)
8 janvier 2019
Achèvement de l'étude (Réel)
8 janvier 2019
Dates d'inscription aux études
Première soumission
28 août 2014
Première soumission répondant aux critères de contrôle qualité
11 septembre 2014
Première publication (Estimation)
15 septembre 2014
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
18 juillet 2019
Dernière mise à jour soumise répondant aux critères de contrôle qualité
15 juillet 2019
Dernière vérification
1 juillet 2019
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- VICC BMT 1426
- P30CA068485 (Subvention/contrat des NIH des États-Unis)
- NCI-2014-01250 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
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