Expired Study
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Cincinnati, Ohio 45220


Purpose:

Prevention of complications in veterans with diabetes depends heavily on assessment of blood glucose and HbA1c. The HbA1c is a blood test that measures the exposure of hemoglobin (Hb) to a person's average blood glucose over the lifespan of a red blood cell (RBC). The test is heavily relied upon as a measure of blood glucose control. It is normally assumed that all people (those with and without diabetes) have a narrow range of red blood cell survival. It has been recently shown that this is not a valid assumption. A more precise test of red blood cell survival, using a biotin label method, demonstrated a substantial difference of red blood cell survival among otherwise normal people. There is sufficient difference in red blood cell survival to alter the estimate of glycemic control from the HbA1c test by as much as 30 per cent. This introduces concern that HbA1c values do not mean the same thing in a significant number of people. Although the evidence is clear that there is variation in RBC survival among people, attributing this variation to differences between individuals depends on answering several simple questions which surprisingly remain unanswered: whether RBC survival is stable over time within an individual and whether blood glucose control affects its stability. Therefore, the goal of the proposed studies is to define these characteristics.


Study summary:

The first Specific Aim tests the hypothesis that mean RBC age is stable in subjects without diabetes and in subjects with diabetes at stable glycemic control. The second Specific Aim tests the hypothesis that mean RBC age will not change in subjects with diabetes studied initially in poor glycemic control, and again after being treated to stable, improved glycemic control for >8 months. To accomplish the two aims, RBC survival and mean blood glucose will be determined at two times separated by at least eight months in 10 subjects without diabetes, 10 subjects with diabetes and stable glycemic control, and up to 15 subjects with diabetes in initial poor glycemic control in order to re-study 10 subjects subsequently in improved glycemic control. The RBC survival will be measured using the same novel biotin RBC label in conjunction with mean glucose determination by continuous glucose monitoring. Mean blood glucose will be assessed using blood glucose testing meter , continuous glucose monitoring equipment, HbA1c, fructosamine and glycated albumin determinations HbA1c is the most highly valued clinical test for long term monitoring of glycemic control and the prediction of diabetes complications risk is relied upon for hundreds of thousands of clinical decisions made every year in veterans with diabetes. The proposed studies, by further defining RBC survival stability necessary to develop a new approach to HbA1c interpretation, therefore has the potential to dramatically support the Department of Veterans Affairs in its mission to reduce the burden of diabetes and its complications


Criteria:

Inclusion Criteria: - Subjects will be between ages 18 and 85 for Aim 1 and between 18 and 80 years for Aim 2 and non-pregnant - Subjects with both types 1 and 2 diabetes - Subjects without diabetes (as determined by an OGTT test at screening) - veterans receiving care at VAMC will be given preference but open to both veterans and non-veterans. Exclusion Criteria: - known hemoglobinopathy or RBC disorder - positive pregnancy test (in women of child-bearing potential or are breast feeding or planning pregnancy during the course of the study; - baseline serum creatinine >1.5 mg/dl - CBC outside the normal range - history of GI blood loss or coagulopathy - urine microalbumin >100 mcg/mg creatinine (spot collection); - transaminases >3 X the upper limit of normal - presence of serum antibodies to biotinylated proteins (which could interfere with the biotin RBC labeling protocol) - greater than or equal to NYHA stage 3 heart failure; - active infection; - known rheumatologic disease - uncontrolled hypo-or hyperthyroidism or an underlying illness known to be associated with either body wasting or changes in serum proteins - plans to move out of the area within the time frame of the Aim for which they are recruited - unwillingness to perform self monitoring of blood glucose


Study is Available At:


Original ID:

ENDA-006-09S


NCT ID:

NCT01204216


Secondary ID:

09100601


Study Acronym:


Brief Title:

Effect of Red Blood Cell Survival on a Commonly Used Diabetes Lab Test-HbA1c


Official Title:

Does Variation in Mean Red Cell Age Impact HbA1C Interpretation?


Overall Status:

Completed


Study Phase:

N/A


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

85 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

VA Office of Research and Development


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

35


Enrollment Type:

Actual


Overall Contact Information

Official Name:Robert M Cohen, MD
Principal Investigator
Cincinnati VA Medical Center, Cincinnati, OH

Study Dates

Start Date:September 1, 2010
Completion Date:September 1, 2016
Completion Type:Actual
Primary Completion Date:July 1, 2016
Primary Completion Type:Actual
Verification Date:September 2017
Last Changed Date:September 1, 2017
First Received Date:September 15, 2010

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Specific Aim 2: To determine the impact of glycemic control on MRBC.
Time Frame:Baseline and 8 months later
Safety Issues:False
Description:Up to 15 subjects participating in Aim 2 will be studied initially in poor glycemic control, while their second biotin/glucose monitoring study will be performed at least 8 months later after achieving stable glycemic control. If RBC survival varies, and
Outcome Type:Primary Outcome
Measure:Specific Aim 1: To determine the stability of MRBC (mean RBC age)over time at stable glycemia. The hypothesis is MRBC will be stable in subjects without diabetes and in subjects with diabetes at stable glycemic control.
Time Frame:Baseline and 8 months later
Safety Issues:False
Description:The investigators will determine MRBC and MBG (by both 7 point profile and continuous glucose monitoring), twice in 10 subjects without diabetes and in 10 subjects with diabetes at stable glycemic control. Since the time course study for following the dis

Study Interventions

Intervention Type:Biological
Name:re-infusion of biotin labeled cells
Description:Subjects will participate in experiments involving re-infusion of biotin-labeled cells in which a small volume (< 10 ml) of autologous, biotinylated erythrocytes will be re-infused to determine cell lifespan and in vivo HbA1c formation rate. These experiments require a series of small, precisely timed post-infusion blood samples over a period of 4 months, with each subject undergoing the procedure twice separated by an interval of at least 8 month
Arm Name:Aim 1
Intervention Type:Biological
Name:Re-infusion of biotin labeled cells
Description:Subjects will participate in experiments involving re-infusion of biotin-labeled cells in which a small volume (< 10 ml) of autologous, biotinylated erythrocytes will be re-infused to determine cell lifespan and in vivo HbA1c formation rate. These experiments require a series of small, precisely timed post-infusion blood samples over a period of 4 months, with each subject undergoing the procedure twice separated by an interval of at least 8 months. small volume (< 10 ml) of autologous,
Arm Name:Aim 2
Intervention Type:Behavioral
Name:Diabetes education/diabetes medication adjustment
Description:Between the initial 3-4 month trial period and the second infusion of biotin labeled cells approximately 8 months later,subjects will receive diabetes education from a CDE. In addition,if needed, diabetes medications may be adjusted by the study endocrinologist to improve subject's glycemic control.
Arm Name:Aim 2

Study Arms

Study Arm Type:Active Comparator
Arm Name:Aim 1
Description:Subjects in this arm will be 10 people without diabetes as well as 10 people with diabetes and stable glycemic control. Subjects will participate in experiments involving re-infusion of biotin-labeled cells in which a small volume (< 10 ml) of autologous, biotinylated erythrocytes will be re-infused to determine cell lifespan and in vivo HbA1c formation rate.
Study Arm Type:Active Comparator
Arm Name:Aim 2
Description:For Aim 2, 10 additional subjects with diabetes in poor glycemic control will be studied initially and then again in improved glycemic control after at least 8 months (with up to 5 additional subjects entered as needed to ensure 10 completed paired studies) to assess the potential role of MRBC variation in the discordances seen between HbA1c and blood glucose testing. Subjects will participate in experiments involving re-infusion of biotin-labeled cells in which a small volume (< 10 ml) of au

Study Agencies

Agency Class:U.S. Fed
Agency Type:Lead Sponsor
Agency Name:VA Office of Research and Development
Agency Class:Other
Agency Type:Collaborator
Agency Name:University of Cincinnati

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation:Cohen RM, Franco RS, Khera PK, Smith EP, Lindsell CJ, Ciraolo PJ, Palascak MB, Joiner CH. Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c. Blood. 2008 Nov 15;112(10):4284-91. doi: 10.1182/blood-2008-04-154112. Epub 2008 Aug 11.
PMID:18694998
Reference Type:Reference
Citation:Cohen RM, Lindsell CJ. When the blood glucose and the HbA(1c) don't match: turning uncertainty into opportunity. Diabetes Care. 2012 Dec;35(12):2421-3. doi: 10.2337/dc12-1479.
PMID:23173128

Data Source: ClinicalTrials.gov

Date Processed: October 09, 2019

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