Clinical trial NCT03415139: Finding the Cause for Post-Transplant Diabetes Mellitus After Allogeneic Hematopoietic Cell Transplant
Official title: Islet Cell and ST2 Axis Dysregulation in Post-Transplant Diabetes Mellitus
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Diabetes Mellitus
Cancer
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
First posted: 2018-01-30
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients without a history of diabetes mellitus undergoing allogeneic hematopoietic stem cell transplantation (HCT).

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.

Detailed description: PRIMARY OBJECTIVES:

I. To determine if changes in islet cell physiology are detectable before or after matched related donor (MRD) hematopoietic stem cell transplant (HCT) in patients developing new-onset post-transplant diabetes mellitus (PTDM).

1. To determine if a compensatory increase in glucose stimulated insulin secretion (GSIS) by β-cells precedes PTDM development in patients without diabetes undergoing MRD HCT.
2. To determine if excess glucagon secretion and impaired α-cell response to glucose or GLP-1 contributes to the hyperglycemia of PTDM.

II. To determine if the IL-33/ST2 axis promotes immune/islet cell dysregulation during PTDM.

OUTLINE:

Patients undergo 2 OGTTs and a standard hyperglycemic clamp procedure prior to HCT. Patients then undergo repeat OGTTs and a hyperglycemic clamp procedure once after HCT between days 80-100.

Eligibility criteria: Inclusion Criteria for Patients:

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

Exclusion Criteria for Patients:

* 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

Additional exclusion criteria (Arms 1 and 2 Aim 1 only):

-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

DONORS Inclusion Criteria for Donors (Arm 1 and Arm 2) Donors undergoing stem cell collection for related allogeneic stem cell transplant

Exclusion Criteria for Donors (Arms 1 and 2):

* 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

Primary outcomes:
measure: 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).
timeFrame: Up to 28 days pre-transplant
measure: 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).
timeFrame: Up to 28 days pre-transplant
measure: Post-transplant glucagon secretion will be measured during the oral glucose tolerance test among patients who do or do not develop PTDM (univariable analysis).
timeFrame: Up to 100 days after transplant
measure: Post-transplant glucagon secretion will be measured during the oral glucose tolerance test among patients who do or do not develop PTDM (multivariable analysis).
timeFrame: Up to 100 days after transplant
measure: Plasma IL-33 levels will be measured among patients who do or do not develop PTDM (univariable analysis).
timeFrame: Up to 100 days after transplant
measure: Plasma IL-33 levels will be measured among patients who do or do not develop PTDM (multivariable analysis).
timeFrame: Up to 100 days after transplant
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Brian G. Engelhardt, M.D.
role: PRINCIPAL_INVESTIGATOR
References: