Diabetes MellitusNCT02240381
Predicting Development of Diabetes Mellitus in Patients Undergoing Allogeneic Stem Cell Transplant
A study testing assessment of therapy complications and laboratory biomarker analysis in people with Diabetes Mellitus and Malignant Neoplasm, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
Trial summary
This clinical trial studies the physiology and immunology of new-onset post-transplant diabetes mellitus in patients undergoing allogeneic stem cell transplantation. Oral glucose tolerance testing (OGTT), euglycemic hyperinsulinemic clamps, and immune assays will be used to define the mechanisms associated with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus, Malignant Neoplasm
- What is being tested?
- assessment of therapy complications and laboratory biomarker analysis
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Nov 2014to 8 Jan 2019
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing MRD allogeneic HCT
- DONOR: Donors undergoing stem cell collection for match related allogeneic stem cell transplant
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
- Unrelated donor, umbilical cord blood, mismatched, or haploidentical transplants
- Patients receiving T cell depletion or thymoglobulin as part of their transplant
- Patients on established, chronic corticosteroid therapy (> 5 mg /day of prednisone or prednisone equivalent) prior to transplant; established, chronic corticosteroid therapy is defined as daily dosing of > 5 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 (> 5 mg/day of prednisone or prednisone equivalent) indefinitely after transplantation
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- 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
- DONOR: Individuals not donating stem cells
- DONOR: Pregnancy or breastfeeding
- DONOR: Inability to give informed consent
- DONOR: 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
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
About this study
Official title: Metabolic and CD4+ T Cell Dysregulation in Post-Transplant Diabetes Mellitus
This clinical trial studies the physiology and immunology of new-onset post-transplant diabetes mellitus in patients undergoing allogeneic stem cell transplantation. Oral glucose tolerance testing (OGTT), euglycemic hyperinsulinemic 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 whether pre-transplant insulin resistance predicts for the development of new onset post-transplant diabetes mellitus (PTDM) in individuals without diabetes undergoing matched related donor (MRD) hematopoietic stem cell transplant (HCT).
II. To define the role of circulating tissue-specific Th1 cells in the development of PTDM.
III. To characterize the phenotype and function of circulating tissue-specific regulatory T cells (Tregs) in HCT recipients with or without PTDM.
OUTLINE:
Patients undergo OGTT and a standard 2-step euglycemic hyperinsulinemic clamp procedure prior to HCT. Patients then undergo repeat OGTT and a 2-step euglycemic hyperinsulinemic clamp procedure once after HCT between days 90-100.
- Conditions
- Diabetes Mellitus, Malignant Neoplasm
- Being tested
- assessment of therapy complications, laboratory biomarker analysis
- 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.
assessment of therapy complicationsProcedure or surgery
During OGTT 75gm of glucose will be given followed by phlebotomy
assessment of therapy complicationsProcedure or surgery
During clamp procedure tritiated glucose, D20, regular insulin will be given, followed by phlebotomy.
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Diagnostic (OGTT, euglycemic hyperinsulinemic clamp) | Experimental | Patients undergo OGTT and a standard 2-step euglycemic hyperinsulinemic clamp procedure prior to HCT. Patients then undergo repeat OGTT and a 2-step euglycemic hyperinsulinemic clamp procedure once after HCT between days 90-100. Receives: Procedure: assessment of therapy complications; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pre-transplant peripheral insulin sensitivity and glucose disposal as defined by the peripheral insulin sensitivity index among patients who do or do not go on to develop PTDM
Patients will be followed for 100 days after transplant for development of diabetes. Wilcoxon rank sum test will be applied to compare the population mean difference between these two groups. Multivariable logistic regression will evaluate whether the peripheral insulin sensitivity index is an independent predictor of PTDM after adjusting for the following covariates: fasting C-peptide level, 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 21 days pre-transplant
Ratio of circulating, gut-homing (alpha4beta7+) Th1 subsets pre-transplant with the development of PTDM after HCT
Wilcoxon rank sum test will be applied to compare the mean difference between these two groups.
Measured: Up to day 100 after transplant
Expression of Helios or glycoprotein A repetitions predominant in alpha4beta7+Foxp3+ Tregs versus alpha4beta7+Foxp3- conventional T cells
Wilcoxon rank sum test or two-sample t-test will be applied to compare the mean difference between two groups. Data will be presented using means and standard deviations for continuous variables, as well as percentage and frequency for categorical variables.
Measured: Up to day 100 after transplant
Secondary outcomes (16)
Changes in hepatic insulin sensitivity among patients with or without established PTDM
Comparison between two independent groups, e.g., with or without PTDM, will be carried out using either two-sample t-test or Wilcoxon rank sum test for continuous variables and Chi-square test or Fisher's exact test for categorical variables.
Measured: Baseline to day 90 after transplant
Changes in peripheral insulin sensitivity among patients with or without established PTDM
Comparison between two independent groups, e.g., with or without PTDM, will be carried out using either two-sample t-test or Wilcoxon rank sum test for continuous variables and Chi-square test or Fisher's exact test for categorical variables.
Measured: Baseline to day 90 after transplant
Changes in OGTT results among patients with or without established PTDM
Comparison between two independent groups, e.g., with or without PTDM, will be carried out using either two-sample t-test or Wilcoxon rank sum test for continuous variables and Chi-square test or Fisher's exact test for categorical variables.
Measured: Baseline to day 90 after transplant
Changes in hepatic insulin sensitivity in the entire cohort
For the comparison of the changes between baseline and day+90 after transplant in the entire cohort, the mean difference will be compared with paired Student's t-test or Wilcoxon signed rank test for continuous variables and a McNemar's test for categorical variables.
Measured: Baseline to day 90 after transplant
Changes in peripheral insulin sensitivity in the entire cohort
For the comparison of the changes between baseline and day+90 after transplant in the entire cohort, the mean difference will be compared with paired Student's t-test or Wilcoxon signed rank test for continuous variables and a McNemar's test for categorical variables.
Measured: Baseline to day 90 after transplant
Changes in OGTT results among patients in the entire cohort
For the comparison of the changes between baseline and day+90 after transplant in the entire cohort, the mean difference will be compared with paired Student's t-test or Wilcoxon signed rank test for continuous variables and a McNemar's test for categorical variables.
Measured: Baseline to day 90 after transplant
Changes in hepatic insulin sensitivity among different groups
To compare the differences between baseline (pre-transplant) and day +90 test results among various groups, linear mixed model will be applied to continuous outcomes (i.e., peripheral insulin sensitivity and hepatic glucose production) and generalized linear mixed model to noncontinuous outcomes (i.e., OGTT results). Groups of interest will be created by stratifying patients based on PTDM, conditioning regimen (ablative vs. reduced intensity) or acute GVHD treated with steroids.
Measured: Baseline to day 90 after transplant
Changes in peripheral insulin sensitivity among different groups
To compare the differences between baseline (pre-transplant) and day +90 test results among various groups, linear mixed model will be applied to continuous outcomes (i.e., peripheral insulin sensitivity and hepatic glucose production) and generalized linear mixed model to noncontinuous outcomes (i.e., OGTT results). Groups of interest will be created by stratifying patients based on PTDM, conditioning regimen (ablative vs. reduced intensity) or acute GVHD treated with steroids.
Measured: Baseline to day 90 after transplant
Changes in OGTT results among different groups
To compare the differences between baseline (pre-transplant) and day +90 test results among various groups, linear mixed model will be applied to continuous outcomes (i.e., peripheral insulin sensitivity and hepatic glucose production) and generalized linear mixed model to noncontinuous outcomes (i.e., OGTT results). Groups of interest will be created by stratifying patients based on PTDM, conditioning regimen (ablative vs. reduced intensity) or acute GVHD treated with steroids.
Measured: Baseline to day 90 after transplant
Ability of pre-transplant or post-transplant tissue-specific Tregs or Th1 cells to predict the development of PTDM
The comparison between independent groups, e.g., with or without PTDM or the three OGTT groups (normal, impaired glucose tolerance, or diabetic), will be carried out using either Wilcoxon rank sum test or Kruskal-Wallis test, respectively.
Measured: Up to day 100 after transplant
Insulin clamp indices
Spearman correlation will be used to evaluate the correlation between insulin clamp indices and Th1/Treg frequencies.
Measured: Up to day 100 after transplant
Th1/Treg frequencies
Spearman correlation will be used to evaluate the correlation between insulin clamp indices and Th1/Treg frequencies.
Measured: Up to day 100 after transplant
Pre-HCT Th1 and Treg tissue-specific subsets
Spearman correlation will evaluate the association between pre-HCT Th1 and Treg tissue-specific subsets with post-HCT donor derived Th1 and Treg.
Measured: Up to 100 days pre-transplant
Ability of alpha4beta7+ Tregs from patients with or without PTDM in suppressing the proliferation of allogeneic T cells
Wilcoxon rank sum test or two-sample t-test will be applied to compare the mean difference between two groups. Data will be presented using means and standard deviations for continuous variables, as well as percentage and frequency for categorical variables. Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity will be made for the parametric test such as t-test and mixed model. If necessary, data will be transformed utilizing appropriate transformations such as the log or square root.
Measured: Up to day 90 after transplant
Ability of effector T cells from patients with PTDM to be resistant to suppression from Tregs obtained from healthy individuals
Wilcoxon rank sum test or two-sample t-test will be applied to compare the mean difference between two groups. Data will be presented using means and standard deviations for continuous variables, as well as percentage and frequency for categorical variables.
Measured: Up to day 100 after transplant
Post-HCT donor derived Th1 and Treg subsets
Spearman correlation will evaluate the association between pre-HCT Th1 and Treg tissue-specific subsets with post-HCT donor derived Th1 and Treg.
Measured: Up to 100 days pre-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2014 (estimated)
- Study start20 Nov 2014
- Primary completion8 Jan 2019
- Study completion8 Jan 2019
Why it stopped: Funding expired
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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Brian Engelhardt, MD, Vanderbilt-Ingram Cancer Center
- Investigators
- Brian Engelhardt, Principal investigator, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02240381
- Sponsor's protocol ID
- VICC BMT 1426
- Other IDs
- NCI-2014-01250, P30CA068485
- Status last verified
- Jul 2019
- First submitted
- 28 Aug 2014
- Last updated
- 18 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic and CD4+ T Cell Dysregulation in Post-Transplant Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT02240381
- Acronym / sponsor ID
- VICC BMT 1426
- Conditions
- Diabetes Mellitus, Malignant Neoplasm
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding expired
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 20 Nov 2014 (actual)
- Primary completion
- 8 Jan 2019 (actual)
- Study completion
- 8 Jan 2019 (actual)
- First posted
- 15 Sep 2014 (estimated)
- 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 trial studies the physiology and immunology of new-onset post-transplant diabetes mellitus in patients undergoing allogeneic stem cell transplantation. Oral glucose tolerance testing (OGTT), euglycemic hyperinsulinemic 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 whether pre-transplant insulin resistance predicts for the development of new onset post-transplant diabetes mellitus (PTDM) in individuals without diabetes undergoing matched related donor (MRD) hematopoietic stem cell transplant (HCT).
II. To define the role of circulating tissue-specific Th1 cells in the development of PTDM.
III. To characterize the phenotype and function of circulating tissue-specific regulatory T cells (Tregs) in HCT recipients with or without PTDM.
OUTLINE:
Patients undergo OGTT and a standard 2-step euglycemic hyperinsulinemic clamp procedure prior to HCT. Patients then undergo repeat OGTT and a 2-step euglycemic hyperinsulinemic clamp procedure once after HCT between days 90-100.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Diagnostic (OGTT, euglycemic hyperinsulinemic clamp) | Experimental | Procedure: assessment of therapy complications, Other: laboratory biomarker analysisPatients undergo OGTT and a standard 2-step euglycemic hyperinsulinemic clamp procedure prior to HCT. Patients then undergo repeat OGTT and a 2-step euglycemic hyperinsulinemic clamp procedure once after HCT between days 90-100. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients undergoing MRD allogeneic HCT
- DONOR: Donors undergoing stem cell collection for match related allogeneic stem cell transplant
Key exclusion criteria (13 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
- Unrelated donor, umbilical cord blood, mismatched, or haploidentical transplants
- Patients receiving T cell depletion or thymoglobulin as part of their transplant
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 |
|---|---|---|
| assessment of therapy complicationsDuring OGTT 75gm of glucose will be given followed by phlebotomy | Procedure or surgery | Diagnostic (OGTT, euglycemic hyperinsulinemic clamp) |
| assessment of therapy complicationsDuring clamp procedure tritiated glucose, D20, regular insulin will be given, followed by phlebotomy. | Procedure or surgery | Diagnostic (OGTT, euglycemic hyperinsulinemic clamp) |
| laboratory biomarker analysisCorrelative studies | Other | Diagnostic (OGTT, euglycemic hyperinsulinemic clamp) |
Primary outcome
Pre-transplant peripheral insulin sensitivity and glucose disposal as defined by the peripheral insulin sensitivity index among patients who do or do not go on to develop PTDM
Time frame: Up to 21 days pre-transplant
Patients will be followed for 100 days after transplant for development of diabetes. Wilcoxon rank sum test will be applied to compare the population mean difference between these two groups. Multivariable logistic regression will evaluate whether the peripheral insulin sensitivity index is an independent predictor of PTDM after adjusting for the following covariates: fasting C-peptide level, 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.
Ratio of circulating, gut-homing (alpha4beta7+) Th1 subsets pre-transplant with the development of PTDM after HCT
Time frame: Up to day 100 after transplant
Wilcoxon rank sum test will be applied to compare the mean difference between these two groups.
Expression of Helios or glycoprotein A repetitions predominant in alpha4beta7+Foxp3+ Tregs versus alpha4beta7+Foxp3- conventional T cells
Time frame: Up to day 100 after transplant
Wilcoxon rank sum test or two-sample t-test will be applied to compare the mean difference between two groups. Data will be presented using means and standard deviations for continuous variables, as well as percentage and frequency for categorical variables.
16 secondary outcomes
Changes in hepatic insulin sensitivity among patients with or without established PTDM
Time frame: Baseline to day 90 after transplant
Changes in peripheral insulin sensitivity among patients with or without established PTDM
Time frame: Baseline to day 90 after transplant
Changes in OGTT results among patients with or without established PTDM
Time frame: Baseline to day 90 after transplant
Changes in hepatic insulin sensitivity in the entire cohort
Time frame: Baseline to day 90 after transplant
Changes in peripheral insulin sensitivity in the entire cohort
Time frame: Baseline to day 90 after transplant
Changes in OGTT results among patients in the entire cohort
Time frame: Baseline to day 90 after transplant
Changes in hepatic insulin sensitivity among different groups
Time frame: Baseline to day 90 after transplant
Changes in peripheral insulin sensitivity among different groups
Time frame: Baseline to day 90 after transplant
Changes in OGTT results among different groups
Time frame: Baseline to day 90 after transplant
Ability of pre-transplant or post-transplant tissue-specific Tregs or Th1 cells to predict the development of PTDM
Time frame: Up to day 100 after transplant
Insulin clamp indices
Time frame: Up to day 100 after transplant
Th1/Treg frequencies
Time frame: Up to day 100 after transplant
Pre-HCT Th1 and Treg tissue-specific subsets
Time frame: Up to 100 days pre-transplant
Ability of alpha4beta7+ Tregs from patients with or without PTDM in suppressing the proliferation of allogeneic T cells
Time frame: Up to day 90 after transplant
Ability of effector T cells from patients with PTDM to be resistant to suppression from Tregs obtained from healthy individuals
Time frame: Up to day 100 after transplant
Post-HCT donor derived Th1 and Treg subsets
Time frame: Up to 100 days pre-transplant
Results and safety
The study was stopped early (reason given: Funding expired). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2019.
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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 Engelhardt principal investigator
Vanderbilt-Ingram Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing assessment of therapy complications and laboratory biomarker analysis in people with Diabetes Mellitus and Malignant Neoplasm, 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 2 inclusion and 13 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: stopped early, as of the sponsor's last update on 18 Jul 2019. 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?
The study was stopped early (reason given: Funding expired). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pre-transplant peripheral insulin sensitivity and glucose disposal as defined by the peripheral insulin sensitivity index among patients who do or do not go on to develop PTDM (time frame: Up to 21 days pre-transplant). The study lists 3 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 18 Jul 2019.