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Predicting Development of Diabetes Mellitus in Patients Undergoing Allogeneic Stem Cell Transplant

15 luglio 2019 aggiornato da: 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.

Panoramica dello studio

Stato

Terminato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

22

Fase

  • Non applicabile

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • Tennessee
      • Nashville, Tennessee, Stati Uniti, 37232
        • Vanderbilt-Ingram Cancer Center

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Terapia di supporto
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.
Altro: analisi di laboratorio dei biomarcatori
Studi correlati
Procedura: assessment of therapy complications
During OGTT 75gm of glucose will be given followed by phlebotomy
Procedura: assessment of therapy complications
During clamp procedure tritiated glucose, D20, regular insulin will be given, followed by phlebotomy.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Changes in hepatic insulin sensitivity among patients with or without established PTDM
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Vanderbilt-Ingram Cancer Center

Collaboratori

National Cancer Institute (NCI)

Investigatori

  • Investigatore principale: Brian Engelhardt, Vanderbilt-Ingram Cancer Center

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

20 novembre 2014

Completamento primario (Effettivo)

8 gennaio 2019

Completamento dello studio (Effettivo)

8 gennaio 2019

Date di iscrizione allo studio

Primo inviato

28 agosto 2014

Primo inviato che soddisfa i criteri di controllo qualità

11 settembre 2014

Primo Inserito (Stima)

15 settembre 2014

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

18 luglio 2019

Ultimo aggiornamento inviato che soddisfa i criteri QC

15 luglio 2019

Ultimo verificato

1 luglio 2019

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • VICC BMT 1426
  • P30CA068485 (Sovvenzione/contratto NIH degli Stati Uniti)
  • NCI-2014-01250 (Identificatore di registro: CTRP (Clinical Trial Reporting Program))

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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