NCT02240381

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
22

participants targeted

Target at below P25 for not_applicable diabetes-mellitus

Timeline
Completed

Started Nov 2014

Longer than P75 for not_applicable diabetes-mellitus

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 28, 2014

Completed
18 days until next milestone

First Posted

Study publicly available on registry

September 15, 2014

Completed
2 months until next milestone

Study Start

First participant enrolled

November 20, 2014

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 8, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 8, 2019

Completed
Last Updated

July 18, 2019

Status Verified

July 1, 2019

Enrollment Period

4.1 years

First QC Date

August 28, 2014

Last Update Submit

July 15, 2019

Conditions

Diabetes MellitusMalignant Neoplasm

Outcome Measures

Primary Outcomes (3)

  • 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

    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

    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

    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

Secondary Outcomes (16)

  • Changes in hepatic insulin sensitivity among patients with or without established PTDM

    Baseline to day 90 after transplant

  • Changes in peripheral insulin sensitivity among patients with or without established PTDM

    Baseline to day 90 after transplant

  • Changes in OGTT results among patients with or without established PTDM

    Baseline to day 90 after transplant

  • Changes in hepatic insulin sensitivity in the entire cohort

    Baseline to day 90 after transplant

  • Changes in peripheral insulin sensitivity in the entire cohort

    Baseline to day 90 after transplant

  • +11 more secondary outcomes

Study Arms (1)

Diagnostic (OGTT, euglycemic hyperinsulinemic clamp)

EXPERIMENTAL

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.

Procedure: assessment of therapy complicationsOther: laboratory biomarker analysis

Interventions

assessment of therapy complicationsPROCEDURE

During OGTT 75gm of glucose will be given followed by phlebotomy

Diagnostic (OGTT, euglycemic hyperinsulinemic clamp)
laboratory biomarker analysisOTHER

Correlative studies

Diagnostic (OGTT, euglycemic hyperinsulinemic clamp)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients undergoing MRD allogeneic HCT
  • DONOR: Donors undergoing stem cell collection for match related allogeneic stem cell transplant

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Diabetes MellitusNeoplasms

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Study Officials

  • Brian Engelhardt

    Vanderbilt-Ingram Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
SUPPORTIVE CARE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor of Medicine, Hematologist/Oncologist, Principal Investigator

Study Record Dates

First Submitted

August 28, 2014

First Posted

September 15, 2014

Study Start

November 20, 2014

Primary Completion

January 8, 2019

Study Completion

January 8, 2019

Last Updated

July 18, 2019

Record last verified: 2019-07

Locations

US(1)