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

Vanderbilt University Medical Center

Status: Enrolling

Conditions: Diabetes Mellitus; Cancer

Treatments: Drug: Hyperglycemic clamp procedure; Drug: Oral Glucose Tolerance Test (OGTT); Drug: 2 OGTTs with and without GLP-1 analogue

Study type: Observational

Funder types: Other

Identifiers

NCT03415139

VICC CTT 1836

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

120 participants in 2 patient groups

Arm 1 for MRD HCT Recipients

Description:

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.

Treatment:

Drug: Hyperglycemic clamp procedure

Drug: Oral Glucose Tolerance Test (OGTT)

Arm 2 for MRD HCT Recipients

Description:

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.

Treatment:

Drug: 2 OGTTs with and without GLP-1 analogue