Diabetes MellitusNCT03415139
Finding the Cause for Post-Transplant Diabetes Mellitus After Allogeneic Hematopoietic Cell Transplant
An observational study of Diabetes Mellitus and Cancer, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Diabetes Mellitus, Cancer
- What is being tested?
- Oral Glucose Tolerance Test (OGTT), 2 OGTTs with and without GLP-1 analogue and Hyperglycemic clamp procedure
- Type of treatment
- Pill or oral medicine
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Mar 2019to Apr 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients without a history of diabetes mellitus undergoing allogeneic hematopoietic stem cell transplantation (HCT).
Who may be able to join
- Patients undergoing allogeneic hematopoietic stem cell transplantation (HCT).
Who cannot join
- 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
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- 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
- 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 locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
VICC Clinical Trials Information Program, 800-811-8480
Brian G. Engelhardt, M.D., 615-936-0381, brian.engelhardt@vumc.org
About this study
Official title: Islet Cell and ST2 Axis Dysregulation in Post-Transplant Diabetes Mellitus
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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).
- 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.
- 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
- Diabetes Mellitus, Cancer
- Being tested
- Oral Glucose Tolerance Test (OGTT), 2 OGTTs with and without GLP-1 analogue, Hyperglycemic clamp procedure
- Medical subject headings
- Diabetes Mellitus, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral Glucose Tolerance Test (OGTT)Drug
A standard OGTT will be performed. During OGTT 75gm of glucose will be given followed by phlebotomy.
2 OGTTs with and without GLP-1 analogueDrug
A standard OGTT will be performed and a second OGTT procedure will be repeated on a different day with GLP-1 analogue.
Hyperglycemic clamp procedureDrug
During the hyperglycemic clamp procedure, D20 will given, followed by phlebotomy.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: 2 OGTTs with and without GLP-1 analogue |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 100 days after transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2018
- Study start12 Mar 2019
- Primary completionApr 2023 (estimated)
- Study completionApr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian Engelhardt, MD, Vanderbilt-Ingram Cancer Center
- Investigators
- Brian G. Engelhardt, M.D., Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03415139
- Sponsor's protocol ID
- VICC CTT 1836
- Status last verified
- Mar 2022
- First submitted
- 15 Jan 2018
- Last updated
- 28 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Islet Cell and ST2 Axis Dysregulation in Post-Transplant Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT03415139
- Acronym / sponsor ID
- VICC CTT 1836
- Conditions
- Diabetes Mellitus, Cancer
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Study start
- 12 Mar 2019 (actual)
- Primary completion
- Apr 2023 (estimated)
- Study completion
- Apr 2025 (estimated)
- First posted
- 30 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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).
- 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.
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 for MRD HCT Recipients | – | Drug: Oral Glucose Tolerance Test (OGTT), Drug: Hyperglycemic clamp procedurePatients 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. |
| Arm 2 for MRD HCT Recipients | – | Drug: 2 OGTTs with and without GLP-1 analoguePatients 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. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients without a history of diabetes mellitus undergoing allogeneic hematopoietic stem cell transplantation (HCT).
Key inclusion criteria (1 listed)
- Patients undergoing allogeneic hematopoietic stem cell transplantation (HCT).
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral Glucose Tolerance Test (OGTT)A standard OGTT will be performed. During OGTT 75gm of glucose will be given followed by phlebotomy. | Drug | Arm 1 for MRD HCT Recipients |
| 2 OGTTs with and without GLP-1 analogueA standard OGTT will be performed and a second OGTT procedure will be repeated on a different day with GLP-1 analogue. | Drug | Arm 2 for MRD HCT Recipients |
| Hyperglycemic clamp procedureDuring the hyperglycemic clamp procedure, D20 will given, followed by phlebotomy. | Drug | Arm 1 for MRD HCT Recipients |
Primary outcome
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).
Time frame: Up to 28 days pre-transplant
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.
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).
Time frame: Up to 28 days pre-transplant
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.
Post-transplant glucagon secretion will be measured during the oral glucose tolerance test among patients who do or do not develop PTDM (univariable analysis).
Time frame: Up to 100 days after transplant
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.
Post-transplant glucagon secretion will be measured during the oral glucose tolerance test among patients who do or do not develop PTDM (multivariable analysis).
Time frame: Up to 100 days after transplant
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.
Plasma IL-33 levels will be measured among patients who do or do not develop PTDM (univariable analysis).
Time frame: Up to 100 days after transplant
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.
Plasma IL-33 levels will be measured among patients who do or do not develop PTDM (multivariable analysis).
Time frame: Up to 100 days after transplant
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian G. Engelhardt, M.D. principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes Mellitus and Cancer, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact VICC Clinical Trials Information Program (800-811-8480, brian.engelhardt@vumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). (time frame: Up to 28 days pre-transplant). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2022.