Application of UCPCR as a Testing Tool for Identification of MODY Patients in the UAE

August 18, 2020 updated by: Imperial College London Diabetes Centre
The study aims to investigate the validity of 2 hour post-prandial UCPCR test in paediatric and adult patients with diabetes duration greater than 2 and 5 years, respectively, for the purposes of distinguishing between patients with type 1 diabetes and MODY in the UAE population.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Urinary C-peptide creatinine ratio (UCPCR) is a non invasive measure of endogenous insulin secretion and has been shown to be effective in identifying Maturity Onset Diabetes of the Young (MODY) from Type 1 Diabetes in adults and paediatric population. Here in the UAE, diabetes prevalence is at 18.9% of the general population and patients are medically treated according to their diabetes type. Currently identification of patients with MODY poses multiple challenges and in some instances results in wrongful diagnosis and treatment of the patients. Most commonly, patients are treated as having type 1 diabetes and given unnecessary insulin injections.

Making correct diabetes diagnosis is pivotal for appropriate disease management. Currently, a set of criteria including age of onset of diabetes (<30 years), BMI<25kg/m2 and absence of islet-cell and GAD auto-antibodies are applied in order to identify potential Maturity Onset Diabetes of the Young (MODY) patients. This has to be followed by genetic testing before final diagnosis is made. Although the set criteria increase the probability of identifying MODY patients, fully discriminating between MODY and type 1 diabetes can still be difficult. As such, some MODY patients (e.g. with mutations in HNF1A or HNF4A genes) are wrongfully treated with insulin when sulphonylureas would be efficient enough for management of their diabetes.

This study will consists of three groups; patients who are autoantibody negative (divided into patients with potential MODY and patients with type 2 diabetes), patients diagnosed with type 1 diabetes and patients who do not have diabetes at the time of recruitment (selected randomly and will include patients with other diagnoses such as IFG and/or IGT). All groups will consist of paediatric patients (≤18 years of age) and adult patients (age of onset of diabetes ≤ 30 years).

The scientific aims of the study are:

  • Validating UCPCR as an in-house test that can potentially be used for clinical purposes.
  • Measuring UCPCR in the study cohort and testing if a cutoff of 0.7nmol/mmol in children and 0.2nmol/mmol in adults will apply to population of interest (ie UAE population).
  • Using operating characteristic curves to identify the optimal UCPCR cut-off for discriminating diabetes subtypes in.
  • Confirming the UCPCR results through genetic analysis of the samples.
  • Validating positive genetic test results by performing mutational analysis on the parents of the patient.
  • Potentially identifying novel MODY mutations in the study population.
  • conducting UCPCR measurements for patients who have been clinically and genetically diagnosed with MODY. This will assist the investigators in confirming the cutoff values for MODY diagnosis.
  • Successfully estimating the background prevalence of MODY in diabetes patients in the Emirates of Abu Dhabi.

Study Type

Observational

Enrollment (Anticipated)

778

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 Arab Emirates
      • Abu Dhabi, United Arab Emirates, 48338
        • Imperial College London Diabetes Centre

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

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients attending Imperial College London Diabetes Centre, UAE.

Description

Inclusion Criteria:

  • patients with age and age of diabetes onset of <18 years
  • patients with age of ≥18 years and age of diabetes onset of ≤30 years

Exclusion Criteria:

- patients with age of ≥18 years and age of diabetes onset of >30 years

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

  • Observational Models: Cohort
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Autoantibody Negative

Patients who are autoantibody negative (could potentially be either MODY or type 2 diabetes patients)

Suspected MODY patients will be candidates for next generation sequencing (NGS)
Genetic: Next generation sequencing (NGS)
Patients will be tested for known MODY genes with specific focus on HNF1A, GCK and HNF4A genes. Furthermore, gene panel testing may be performed for any known diabetes genes.If the results are negative, WES/WGS will be performed in patients suspected of having MODY for identification of novel MODY mutations.
Other Names:
  • NGS panel
  • Whole exome/genome sequencing (WES/WGS)
Diabetes Mellitus, Type 1

Patients diagnosed with type 1 diabetes mellitus

Patients with positive UCPCR and negative autoantibodies results will be suspected with MODY and will be candidates for next generation sequencing (NGS)
Genetic: Next generation sequencing (NGS)
Patients will be tested for known MODY genes with specific focus on HNF1A, GCK and HNF4A genes. Furthermore, gene panel testing may be performed for any known diabetes genes.If the results are negative, WES/WGS will be performed in patients suspected of having MODY for identification of novel MODY mutations.
Other Names:
  • NGS panel
  • Whole exome/genome sequencing (WES/WGS)
Non Diabetic
Individuals not diagnosed with any type of diabetes (but could be diagnosed with IFG and/or IGT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urinary C-peptide Creatinine Ratio (UCPCR)
Time Frame: 2 hours post-prandial
Measuring UCPCR in our study cohort and testing if a cutoff of 0.7nmol/mmol in children and 0.2nmol/mmol in adults will apply to our population of interest (ie UAE population).
2 hours post-prandial

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Receiver operating characteristic (ROC) curve
Time Frame: through study completion, an average of 1 year
Using receiver operating characteristic (ROC) curves to identify the optimal UCPCR cut-off for discriminating diabetes subtypes in our study population.
through study completion, an average of 1 year
Genetic analysis
Time Frame: through study completion, an average of 2 year
Confirming our UCPCR results through genetic analysis of the samples.
through study completion, an average of 2 year
Positive genetic result analysis
Time Frame: through study completion, an average of 2 year
Validating positive genetic test results by performing mutational analysis on the parents of the patient.
through study completion, an average of 2 year
Novel MODY genes and mutations
Time Frame: through study completion, an average of 2 year
Identifying novel MODY genes and/or mutations in the study population through next generation sequencing methodologies
through study completion, an average of 2 year
UCPCR measurements
Time Frame: through study completion, an average of 2 year
Conducting UCPCR measurements for patients who have been clinically and genetically diagnosed with MODY. This will assist us in confirming the cutoff values for MODY diagnosis.
through study completion, an average of 2 year
Prevalence of MODY
Time Frame: through study completion, an average of 2 year
Estimating the background prevalence of MODY in diabetes patients in the Emirates of Abu Dhabi.
through study completion, an average of 2 year

Collaborators and Investigators

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

Sponsor

Imperial College London Diabetes Centre

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 (Actual)

April 1, 2015

Primary Completion (Anticipated)

December 31, 2021

Study Completion (Anticipated)

December 31, 2021

Study Registration Dates

First Submitted

June 26, 2018

First Submitted That Met QC Criteria

July 22, 2018

First Posted (Actual)

July 31, 2018

Study Record Updates

Last Update Posted (Actual)

August 19, 2020

Last Update Submitted That Met QC Criteria

August 18, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IREC018

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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