Finding the Cause for Post-Transplant Diabetes Mellitus After Allogeneic Hematopoietic Cell Transplant

NCT03415139 | Unknown DMC FDA Drug

• 1 other identifier: VICC CTT 1836
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical research studies the physiology and immunology of new-onset post-transplant diabetes mellitus in patients undergoing allogeneic stem cell transplantation. Oral glucose tolerance tests (OGTT), hyperglycemic 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.

Conditions

Diabetes Mellitus; Cancer

Outcome Measures

Primary Outcomes (6)

• Pre-transplant insulin secretion will be measured as glucose stimulated insulin secretion (GSIS) during a hyperglycemic clamp procedure among patients who do or do not go on to develop PTDM (univariable analysis).

  A hyperglycemic clamp procedure will be performed pre-transplant. Pre-transplant will be defined as no more than 28 days before allogeneic hematopoietic cell transplantation. Patients will then be followed for 100 days after transplant for development of diabetes. In univariable analysis, a Wilcoxon rank sum test will be applied to compare the population mean difference in GSIS between these two groups.

  Up to 28 days pre-transplant

• Pre-transplant insulin secretion will be measured as glucose stimulated insulin secretion (GSIS) during a hyperglycemic clamp procedure among patients who do or do not go on to develop PTDM (multivariable analysis).

  A hyperglycemic clamp procedure will be performed pre-transplant. Pre-transplant will be defined as no more than 28 days before allogeneic hematopoietic cell transplantation. Patients will then be followed for 100 days after transplant for development of diabetes. In multivariable analysis, logistic regression will evaluate whether GSIS is an independent predictor of PTDM after adjusting for the following covariates: gender, 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 28 days pre-transplant

• Post-transplant glucagon secretion will be measured during the oral glucose tolerance test among patients who do or do not develop PTDM (univariable analysis).

  Patients will be followed for 100 days after transplant for development of diabetes. In univariable analysis, a Wilcoxon rank sum test will be applied to compare the population mean difference in glucagon secretion between these two groups.

  Up to 100 days after transplant

• Post-transplant glucagon secretion will be measured during the oral glucose tolerance test among patients who do or do not develop PTDM (multivariable analysis).

  Patients will be followed for 100 days after transplant for development of diabetes. In multivariable analysis, a logistic regression will evaluate whether glucagon secretion is independently associated with PTDM after adjusting for the following covariates: gender, 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 100 days after transplant

• Plasma IL-33 levels will be measured among patients who do or do not develop PTDM (univariable analysis).

  Patients will be followed for 100 days after transplant for development of diabetes. In univariable analysis, a Wilcoxon rank sum test will be applied to compare the population mean difference in IL-33 between these two groups.

  Up to 100 days after transplant

• Plasma IL-33 levels will be measured among patients who do or do not develop PTDM (multivariable analysis).

  In multivariable analysis, logistic regression will evaluate whether IL-33 is independently associated with PTDM after adjusting for the following covariates: gender, 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 100 days after transplant

Study Arms (2)

Arm 1 for MRD HCT Recipients

Patients undergo an Oral Glucose Tolerance Test (OGTT) and 1 hyperglycemic clamp will be performed on separate days prior to transplant and then each procedure will be repeated once between day+80 to day+100 (+/- 10 days) after transplant.

Drug: Oral Glucose Tolerance Test (OGTT); Drug: Hyperglycemic clamp procedure

Arm 2 for MRD HCT Recipients

Patients undergo 2 Oral Glucose Tolerance Test (OGTTs) (with and without GLP-1 analogue) will be performed on separate days prior to transplant and then each procedure will be repeated once between day+80 to day+100 (+/- 10 days) after transplant.

Drug: 2 OGTTs with and without GLP-1 analogue

Interventions

Oral Glucose Tolerance Test (OGTT) DRUG

A standard OGTT will be performed. During OGTT 75gm of glucose will be given followed by phlebotomy.

Arm 1 for MRD HCT Recipients

2 OGTTs with and without GLP-1 analogue DRUG

A standard OGTT will be performed and a second OGTT procedure will be repeated on a different day with GLP-1 analogue.

Arm 2 for MRD HCT Recipients

Hyperglycemic clamp procedure DRUG

During the hyperglycemic clamp procedure, D20 will given, followed by phlebotomy.

Arm 1 for MRD HCT Recipients

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients without a history of diabetes mellitus undergoing allogeneic hematopoietic stem cell transplantation (HCT).

You may qualify if:

• Patients undergoing allogeneic hematopoietic stem cell transplantation (HCT).

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
• Umbilical cord blood transplants
• Patients on established, chronic corticosteroid therapy (\> 10 mg /day of prednisone or prednisone equivalent) prior to transplant; established, chronic corticosteroid therapy is defined as daily dosing of \> 10 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 (\> 10 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
• Diagnosis of diabetes by standard oral glucose tolerance testing prior to transplant (2-hour plasma glucose value ≥ 200 mg/dL) in either Arm 1 or 2 will exclude further testing as per Aim 1. Immunological / metabolic testing as per Aim 2 will still be allowed
• Individuals not donating stem cells
• Pregnancy or breastfeeding
• Inability to give informed consent
• Any condition which, in the opinion of the investigator, might interfere with study objective

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum / plasma and peripheral blood mononuclear cells will be collected before and after hematopoietic stem cell transplant (HCT)

MeSH Terms

Conditions

Diabetes Mellitus; Neoplasms

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Study Officials

• Brian G. Engelhardt, M.D.

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

VICC Clinical Trials Information Program

CONTACT

800-811-8480; brian.engelhardt@vumc.org

Brian G. Engelhardt, M.D.

CONTACT

615 936-0381; brian.engelhardt@vumc.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: January 15, 2018
• First Posted: January 30, 2018
• Study Start: March 12, 2019
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2025
• Last Updated: March 28, 2022

Record last verified: 2022-03

Locations

US (1)