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

NCT ID: NCT03415139

Last Updated: 2022-03-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

120 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-03-12

Study Completion Date

2025-04-30

Brief Summary

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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

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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.

Conditions

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Diabetes Mellitus Cancer

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Oral Glucose Tolerance Test (OGTT)

Intervention Type DRUG

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

Hyperglycemic clamp procedure

Intervention Type DRUG

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

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.

2 OGTTs with and without GLP-1 analogue

Intervention Type DRUG

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

Interventions

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Oral Glucose Tolerance Test (OGTT)

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

Intervention Type DRUG

2 OGTTs with and without GLP-1 analogue

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

Intervention Type DRUG

Hyperglycemic clamp procedure

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

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
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Brian Engelhardt, MD

Associate Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Brian G. Engelhardt, M.D.

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

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Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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VICC Clinical Trials Information Program

Role: CONTACT

800-811-8480

Brian G. Engelhardt, M.D.

Role: CONTACT

615 936-0381

Facility Contacts

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VICC Clinical Trials Information Program

Role: primary

800-811-8480

Brian G. Engelhardt, M.D.

Role: backup

615-936-0381

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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VICC CTT 1836

Identifier Type: -

Identifier Source: org_study_id

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