Clinical trial NCT02240381: Predicting Development of Diabetes Mellitus in Patients Undergoing Allogeneic Stem Cell Transplant
Official title: Metabolic and CD4+ T Cell Dysregulation in Post-Transplant Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Diabetes Mellitus
Malignant Neoplasm
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-09-15
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Up to 21 days pre-transplant
measure: Ratio of circulating, gut-homing (alpha4beta7+) Th1 subsets pre-transplant with the development of PTDM after HCT
timeFrame: Up to day 100 after transplant
measure: Expression of Helios or glycoprotein A repetitions predominant in alpha4beta7+Foxp3+ Tregs versus alpha4beta7+Foxp3- conventional T cells
timeFrame: Up to day 100 after transplant
Secondary outcomes:
measure: Changes in hepatic insulin sensitivity among patients with or without established PTDM
timeFrame: Baseline to day 90 after transplant
measure: Changes in peripheral insulin sensitivity among patients with or without established PTDM
timeFrame: Baseline to day 90 after transplant
measure: Changes in OGTT results among patients with or without established PTDM
timeFrame: Baseline to day 90 after transplant
measure: Changes in hepatic insulin sensitivity in the entire cohort
timeFrame: Baseline to day 90 after transplant
measure: Changes in peripheral insulin sensitivity in the entire cohort
timeFrame: Baseline to day 90 after transplant
measure: Changes in OGTT results among patients in the entire cohort
timeFrame: Baseline to day 90 after transplant
measure: Changes in hepatic insulin sensitivity among different groups
timeFrame: Baseline to day 90 after transplant
measure: Changes in peripheral insulin sensitivity among different groups
timeFrame: Baseline to day 90 after transplant
measure: Changes in OGTT results among different groups
timeFrame: Baseline to day 90 after transplant
measure: Ability of pre-transplant or post-transplant tissue-specific Tregs or Th1 cells to predict the development of PTDM
timeFrame: Up to day 100 after transplant
measure: Insulin clamp indices
timeFrame: Up to day 100 after transplant
measure: Th1/Treg frequencies
timeFrame: Up to day 100 after transplant
measure: Pre-HCT Th1 and Treg tissue-specific subsets
timeFrame: Up to 100 days pre-transplant
measure: Ability of alpha4beta7+ Tregs from patients with or without PTDM in suppressing the proliferation of allogeneic T cells
timeFrame: Up to day 90 after transplant
measure: Ability of effector T cells from patients with PTDM to be resistant to suppression from Tregs obtained from healthy individuals
timeFrame: Up to day 100 after transplant
measure: Post-HCT donor derived Th1 and Treg subsets
timeFrame: Up to 100 days pre-transplant
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Brian Engelhardt
role: PRINCIPAL_INVESTIGATOR
References: