Exhaled Carbon Monoxide and Red Blood Cell Turnover

NCT03288233 | Unknown

• 1 other identifier: CR2_2015-1070
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Hemoglobin A1C (HbA1c) is the cornerstone of blood sugar monitoring. As HbA1c is formed by the covalent reaction of glucose with hemoglobin throughout the lifespan of the red blood cell (RBC), it is used as a surrogate marker for integrated mean blood glucose over time. The HbA1c value therefore is dependent on the average amount of time the RBC spends in the circulation (mean RBC age or MRBC). However, our previous studies measuring red cell lifespan using either an age cohort label (ex vivo labeling with biotin) or a population label (stable isotope) have demonstrated, contrary to established dogma, that the MRBC varies substantially among individuals and is sufficiently variable to affect HA1c interpretation in a significant percentage of individuals with diabetes. Although the stable isotope method is suitable for clinical studies, it has limited potential for application to large population of subjects. A potential alternative to the stable isotope approach that could be applied routinely to the average patient in the clinic is measurement of exhaled carbon monoxide (eCO) concentration, a reflection of RBC heme turnover. In general, the primary advantage of applying exhaled breath analyses to human clinical diagnostics and therapeutic monitoring is that this technique is noninvasive, safe, simple, and provides near-real time measurements. The purpose of this observational study is to optimize the collection of eCO in a normal control population followed by measurement in a cohort of subjects previously assessed by either the SI or biotin methods for comparison.

Conditions

Diabetes Mellitus; Healthy

Keywords

Hemoglobin A1c; HbA1c; End tidal carbon monoxide

Outcome Measures

Primary Outcomes (4)

• Average end expiratory alveolar concentration of Carbon monoxide (ppm) in morning before breakfast

  In this preliminary phase of the study we use a device that has not been used in the United States before (Carbolyzer II, Taiyo, Japan) as a surrogate marker for red blood cell (RBC) removal or turnover in human subjects. Published studies and the company literature for the Carbolyzer mBA-2000 would suggest sufficient capability for the purposes of such measurements. This project will test more rigorously the validity of these specifications for this application. First, the detector will be standardized in more detail with measurement of the CO content of defined mixtures in the range needed for sufficient sensitivity. The device will calibrated prior with known concentrations of a mixture of carbon monoxide in air at three points (0-3-12 ppm). In addition, investigators will evaluate alternative CO detection devices for suitability which do not alter the experience of the participating subject or the accompanying risks and benefits.

  four consecutive weeks

• Average end expiratory alveolar concentration of CO (ppm) in morning 30 min after breakfast

  similar to outcome 1

  four consecutive weeks

• Average end expiratory alveolar concentration of CO (ppm) 30 min after lunch

  similar to outcome 1

  one day sampling

• Average end expiratory alveolar concentration of CO (ppm) 5 hours after lunch

  similar to outcome 1

  one day sampling

Study Arms (1)

Primary Group

Diagnostic Test: Breath carbon monoxide measurement

Interventions

Breath carbon monoxide measurement DIAGNOSTIC_TEST

Participants will be asked to breath in designed breathing circuits or hold their breath for short period of time and then their breath samples will be collected in special bags and the carbon monoxide and carbon dioxide will be measured with electrochemical techniques.

Primary Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy adults with Diabetes aged 18 to 75 years previously measured for red blood cell lifespan

You may qualify if:

• Subjects will be between age 18 and 75 years, non-pregnant, with a goal of equal gender and race (Caucasian vs. African-American) distribution

You may not qualify if:

• 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
• lung transplantation, irradiation, recent surgery, recent intensive care admission, asthma, COPD, cystic fibrosis, smoking, recent hematoma, uncontrolled hypo- or hyperthyroidism or an underlying illness known to be associated with either body wasting or changes in serum proteins (e.g. certain malignancies including multiple myeloma or tuberculosis).

Sponsors & Collaborators

• University of Cincinnati: lead
• VA Office of Research and Development: collaborator

Study Sites (1)

University of Cincinnati

Cincinnati, Ohio, 45220, United States

RECRUITING

Related Publications (3)

• Khera PK, Smith EP, Lindsell CJ, Rogge MC, Haggerty S, Wagner DA, Palascak MB, Mehta S, Hibbert JM, Joiner CH, Franco RS, Cohen RM. Use of an oral stable isotope label to confirm variation in red blood cell mean age that influences HbA1c interpretation. Am J Hematol. 2015 Jan;90(1):50-55. doi: 10.1002/ajh.23866.

  PMID: 25293624 BACKGROUND

• Coburn RF. The measurement of endogenous carbon monoxide production. J Appl Physiol (1985). 2012 Jun;112(11):1949-55. doi: 10.1152/japplphysiol.00174.2012. Epub 2012 Mar 22.

  PMID: 22442030 BACKGROUND

• Strocchi A, Schwartz S, Ellefson M, Engel RR, Medina A, Levitt MD. A simple carbon monoxide breath test to estimate erythrocyte turnover. J Lab Clin Med. 1992 Sep;120(3):392-9.

  PMID: 1517686 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Robert Cohen, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shahriar Arbabi, MD

CONTACT

513-558-3088; shahriar.arbabi@uc.edu

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 8, 2017
• First Posted: September 20, 2017
• Study Start: April 1, 2015
• Primary Completion: May 1, 2018
• Study Completion: August 1, 2018
• Last Updated: September 20, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)