- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01204216
Effect of Red Blood Cell Survival on a Commonly Used Diabetes Lab Test-HbA1c
Does Variation in Mean Red Cell Age Impact HbA1C Interpretation?
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 Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Ohio
-
Cincinnati, Ohio, United States, 45220
- Cincinnati VA Medical Center, Cincinnati, OH
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Aim 1
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.
|
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 |
Active Comparator: Aim 2
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 autologous, biotinylated erythrocytes will be re-infused to determine cell lifespan and in vivo HbA1c formation rate.
|
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, biotinylated erythrocytes will be re-infused to determine cell lifespan and in vivo HbA1c formation rate.
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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 disappearance of re-infused labeled RBCs is approximately 4 months, performing the biotin labeling of the cells for the second study at least 8 months after completion of sampling for the first, effectively samples MRBC at two time points at least one year apart.
|
Baseline and 8 months later
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Specific Aim 2: To Determine the Impact of Glycemic Control on MRBC.
Time Frame: Baseline and 8 months later
|
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 in particular if it varies with glycemic control, then the relationship between HbA1c and MBG will change.
Several studies have reported that HbA1c rises linearly with MBG until there is the appearance of a plateau suggesting a saturation maximum.
|
Baseline and 8 months later
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Robert M Cohen, MD, Cincinnati VA Medical Center, Cincinnati, OH
Publications and helpful links
General Publications
- 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.
- 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. No abstract available.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ENDA-006-09S
- 09100601 (Other Grant/Funding Number: University of Cincinnati)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Diabetes Mellitus
-
University of Colorado, DenverMassachusetts General Hospital; Beta Bionics, Inc.CompletedDiabetes Mellitus, Type 1 | Type 1 Diabetes | Diabetes type1 | Type 1 Diabetes Mellitus | Autoimmune Diabetes | Diabetes Mellitus, Insulin-Dependent | Juvenile-Onset Diabetes | Diabetes, Autoimmune | Insulin-Dependent Diabetes Mellitus 1 | Diabetes Mellitus, Insulin-Dependent, 1 | Diabetes Mellitus, Brittle | Diabetes Mellitus, Juvenile-Onset and other conditionsUnited States
-
Guang NingRecruitingType 2 Diabetes Mellitus | Type1 Diabetes Mellitus | Monogenetic Diabetes | Pancreatogenic Diabetes | Drug-Induced Diabetes Mellitus | Other Forms of Diabetes MellitusChina
-
Medical College of WisconsinMedical University of South CarolinaCompletedDiabetes Mellitus | Type 2 Diabetes Mellitus | Adult-Onset Diabetes Mellitus | Non-Insulin-Dependent Diabetes Mellitus | Noninsulin Dependent Diabetes Mellitus, Type IIUnited States
-
Hanmi Pharmaceutical Company LimitedUnknownType2 Diabetes Mellitus | Type1 Diabetes MellitusUnited States
-
Meir Medical CenterCompletedDiabetes Mellitus Type 2 | Diabetes Mellitus, Non-insulin Dependant | Diabetes Mellitus, on Oral Hypoglycemic Treatment | Adult Type Diabetes MellitusIsrael
-
Peking Union Medical College HospitalUnknownType 2 Diabetes Mellitus | Type 1 Diabetes Mellitus | Gestational Diabetes Mellitus | Pancreatogenic Diabetes Mellitus | Pregestational Diabetes Mellitus | Diabetes Patients in Perioperative PeriodChina
-
SanofiCompletedType 1 Diabetes Mellitus-Type 2 Diabetes MellitusHungary, Russian Federation, Germany, Poland, Japan, United States, Finland
-
Medical University of South CarolinaNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)CompletedDiabetes Mellitus, Type 2 | Diabetes Mellitus, Type II | Diabetes Mellitus, Adult-Onset | Diabetes Mellitus, Non-Insulin-Dependent | Diabetes Mellitus, Noninsulin DependentUnited States
-
Joslin Diabetes CenterCambridge Medical Technologies, LLCCompletedType 2 Diabetes Mellitus | Type1 Diabetes MellitusUnited States
-
Medical College of WisconsinMedical University of South Carolina; National Institute of Diabetes and Digestive...Active, not recruitingDiabetes Mellitus, Type 2 | Diabetes Mellitus, Type II | Diabetes Mellitus, Adult-Onset | Diabetes Mellitus, Non-Insulin-Dependent | Diabetes Mellitus, Noninsulin DependentUnited States
Clinical Trials on re-infusion of biotin labeled cells
-
Gladwin, Mark, MDNational Heart, Lung, and Blood Institute (NHLBI)Terminated
-
National Heart, Lung, and Blood Institute (NHLBI)Children's National Research InstituteRecruitingSickle Cell Disease | Thalassemia | HemoglobinopathyUnited States
-
Emory UniversityNational Heart, Lung, and Blood Institute (NHLBI)Completed
-
Emory UniversityNational Heart, Lung, and Blood Institute (NHLBI); Cerus CorporationRecruiting
-
Guohua AnCompleted
-
Damascus UniversityRecruitingCoronary Artery Disease | Cardiovascular Complication | Blood Transfusion ComplicationSyrian Arab Republic
-
University of ZurichCompletedMalignant Pleural MesotheliomaSwitzerland
-
Xiaoyan ZhangCompletedMalignant Solid TumorChina
-
Dana-Farber Cancer InstituteNational Cancer Institute (NCI); Beth Israel Deaconess Medical Center; Brigham...CompletedHematologic MalignancyUnited States
-
Shanghai Public Health Clinical CenterActive, not recruitingRenal Cell Carcinoma | Small Cell Lung Cancer | Hepatocellular Carcinoma | Gastric Cancer | Non-small Cell Lung Cancer | Pancreas CancerChina