N2-(1-carboxyethyl)-2'Deoxyguanosine (CEdG) a Potential Biomarker for Diabetes

November 1, 2019 updated by: City of Hope Medical Center

Evaluation of the Internal Consistency of Measurement and Potential of a DNA-adduct as a Biomarker of Glycemic Control

The purpose of this study is to see if the CEdG assay can produce internally consistent results and initiate its validation as a biomarker for diabetes in humans.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Primary Objective is to replicate and validate the CEdG assay to be used in human subjects. A fully automated assay for urinary CEdG has been developed. the investigators will validate the observations made in diabetic animal models in human subjects with and without type 2 diabetes mellitus (T2DM). Specifically, the investigators will investigate and establish the inter- and intra-assay coefficients of variability in human subjects.

Secondary Objective is to determine the correlation between CEdG levels and hemoglobulin A1c (HbA1c) in human subjects with T2DM and the response to diabetic treatment and to define the relationship of CEdG with diabetic complications. The investigators will examine the relationship of CEdG with glycemic control, based on HbA1c, which is the current gold standard, in both patients with type 1 and type 2 diabetes. The investigators also compare the changes in CEdG and Hb1Ac levels in response to diabetic treatment in diabetic patients. The relationship of CEdG with diabetic complications will also be investigated in diabetic patients.

Statistical considerations for the primary objective:

Sample Size: Because there are many more variables in human subjects, the investigators calculated the sample size based on a much more conservative assumption than what the investigators observed from diabetic animal models. The investigators are planning a study of a continuous response variable from independent control and experimental subjects with 1 control per experimental subject. Based on the animal data, the investigators expect the results within each subject group to be normally distributed with a standard deviation of 0.3. If the true difference in the mean between the diabetic and non-diabetic groups is 0.5, the investigators will need to study 9 diabetic and 9 non-diabetic subjects to be able to reject the null hypothesis that the population means of the experimental and control groups are equal with probability (power) 0.9. The Type I error probability associated with this test of this null hypothesis is 0.05. To account for a possible attrition rate of 30%, the investigators will accrue 12 diabetic and 12 non-diabetic subjects to the study.

Statistical Analysis: The effect of diabetic status on urinary CEdG levels will be compared using a Student's t-test. Differences in continuous variables between the groups of subjects will be tested with either one-way ANOVA or Student's t-test when appropriate. Differences in proportions will be evaluated by a chi-square test. The continuous variables, that fail the Normality test, will be logarithmically transformed before analysis. To examine the influence of confounding variables, a stepwise regression analysis will be used. A p value less than 0.05 will be considered statistically significant.

According to the NIH guidelines for validation of analytical methods for biomarkers used in drug development, for small molecules, bioanalytical assays where the analytical run is accepted as valid when at least 67% (4/6) of the quality controls fall within 15% of their nominal value. The consistency of 6 repeated runs will be evaluated by Grubbs test for repeatability within each subject. The overall consistency of CEdG measures can be quantified by the proportion of subjects with 1+ identified outliers among the 6 repeated runs. To obtain a baseline estimate of the consistency of the CEdG assay, the investigators will take the number of those six measurements that fall within 15% of the mean as our outcome measure. Definitive validation of a biomarker will require definitive quantitative or relative quantitative assay approaches.

Statistical considerations for the secondary objective:

The investigators will regress study participants' values of y-var (HbA1c) against x-var (CEdG). Prior data indicate that the standard deviation of x-var is 0.15 and the standard deviation of the regression errors will be 0.15. If the true slope of the line obtained by regressing y-var against x-var is 0.3, the investigators will need to study 89 subjects to be able to reject the null hypothesis that this slope equals zero with probability (power) 0.8. The Type I error probability associated with this test of this null hypothesis is 0.05. Therefore, 100 subjects will be recruited for the study to account for potential attrition of subjects.

Patient demographic and clinic characteristics will be tabulated using statistics of mean, standard deviation, median, range, number and percentage when appropriate. CEdG data will be analyzed as a continuous or transformed variable for the measured expression level. The univariate correlation between the CEdG expression and each quantitative clinical measure will be evaluated using Pearson correlation and its 95% confidence interval. The time trend in longitudinal data and its possible interaction with other risk factors will be explored using boxplots, fitted curves, generalized linear models, and generalized estimating equations as appropriate. Estimated correlations between CEdG data and clinical endpoints, and its possible time trends during the 12 month period will provide valuable information for choosing the primary endpoint and sample size in a future larger scale correlation study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
26

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 18 years of age or older
  • Registered patient of City of Hope
  • Documentation of a diagnosis of diabetes identified by the problem list in the patient's electronic health record

Exclusion Criteria:

  • Current pregnancy
  • An active diagnosis of cancer, as CEdG levels may potentially be affected by malignant processes

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: DIAGNOSTIC
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
NO_INTERVENTION: Diabetes, Non-diabetes
Other: N2-(1-carboxyethyl)-2'deoxyguanosine (CEdG)

Glucose and its adducts, such as HbA1c, decompose non-enzymatically to yield α-oxo-aldehydes are up to 20,000 x more reactive than the parent molecule. Amounts of an α-oxo-aldehyde, methylglyoxal (MG), are elevated up to 6-fold in patients with Type 1 dm. Quantitation of MG, but MG does form stable, irreversible adducts termed "advanced glycation endproducts" (AGEs) that can be measured. MG also reacts with DNA to yield primarily one stable DNA-AGE, CEdG, and suggests that measuring CEdG might allow for a direct method for assessing glycemic status and α-oxo-aldehyde burden.

Investigators have shown that CEdG levels are significantly elevated in urine and tissue of Type 1 & 2 dm animal models. DNA-AGE may correlate with the development of diabetes complications and identify patients at higher risk. Therefore, the investigators hypothesize that CEdG, a DNA-AGE, can be used as a marker of diabetes control and complications.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Percentage of quality controls that fall within 15% of the nominal value for a analytical run of the CEdG assay.
Time Frame: One time urine collection
One time urine collection

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Correlation of Hemoglobin A1c and CEdG levels
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
City of Hope Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: John Termini, PhD, City of Hope Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2014

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 11, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 11, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 31, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 13, 2014

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 19, 2014

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 5, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 1, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 13188

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.

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