Human Solute Carrier Family 5 Member 2 (SLC5A2) Deficiency and the Glucagon-Incretin Axis

May 27, 2019 updated by: Medical University Innsbruck

Human SLC5A2 Deficiency and the Glucagon-Incretin Axis: A Pilot Study

Sodium-glucose-cotransporter 2 (SGLT2) are a new type of oral antidiabetic drugs. SGLT2 inhibitors increase the urinary glucose excretion and thereby decrease blood glucose levels. Beside their glucose lowering effects SGLT2 inhibitors showed beneficial effects on the cardiovascular health. But several studies in cell culture and mice showed that the physiological inhibition of glucagon after meal consumption is impaired when using SGLT2 inhibitors.

The patients carry a rare genetical disease called Familial renal glucosuria (FRG), a human model of life long SGLT2 inhibition. To elucidate the effects of partial and complete SGLT2 inhibition in humans the investigators perform a mixed-meal tolerance test (MMTT), the gold standard for elucidation of insulin and glucagon dynamics.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The index patient was referred to the Department of Internal Medicine I at the Medical University of Innsbruck for evaluation of unclear glucosuria in combination with normal blood glucose levels. The patient suffered from recurrent urinary tract infections and increased urinary frequency, showed a physiological hemoglobin A1c and no further signs of renal dysfunction. Sequencing of the SLC5A2 coding region confirmed that the patient was compound heterozygous for two SLC5A2 mutations. The patient is a mother of five healthy children which are willing to take part in the test. The children show a 50/50 distribution of the mother's mutations. The MMTT will take place after 48 hours of alcohol, sport abstinence and an overnight fasting period. The patients will be given 6 ml/kg body weight of a standardized liquid meal. Blood samples will be collected 10 minutes before consumption of the meal, at the time point of consumption and 15, 30, 60, 120, 150, 180, 210 and 240 minutes after consumption. At each time point six blood tubes will be taken, except at time point -10 and 240 minutes, there is one sample more collected. The investigators aim to assess glucagon, insulin, c-peptide, gastric inhibitory polypeptide (GIP), Glucagon-like peptide-1 (GLP-1), Glucagon-like peptide-2 (GLP-2) levels.

Glucose tolerance will be assessed by using the 4 hours area under the curve (AUC) for glucose. To evaluate the beta-cell function the 4h-AUC's for insulin, c-peptide and the 4h-AUC insulin:glucose ratio will be calculated and compared. The calculation of the alpha-cell function will be performed with the AUC of glucagon and the AUC glucagon/glucose ratio. GIP, GLP-1 and GLP-2 will be determined using the AUC. The AUC's will be calculated by the trapezoidal method.

Study Type

Observational

Enrollment (Anticipated)

10

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

  • Austria
    • Tyrol
      • Innsbruck, Tyrol, Austria, 6020
        • Recruiting
        • Medical University Innsbruck
        • Contact:

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

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

One compound heterozygous female index patient and four heterozygous children. The control group consists of age, sex and BMI matched participants from nearly the same area to avoid environmental factors.

Description

Inclusion Criteria:

  • At least 18 years
  • Capable of giving consent
  • One or more SLC5A2 mutations leading to FRG
  • Written consent

Exclusion Criteria:

  • Impaired glucose tolerance
  • Diabetes mellitus

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients
Patients carrying one or both mutations.
Other: Mixed-meal-tolerance-test
To assess the dynamics of the glucagon-incretin axis we need to perform the MMTT. Thereby the patients need to consume a body weight adjusted, standardized meal and we draw blood at fixed time points over 4 hours.
Controls
Patients not carrying a mutation Familial renal glucosuria causing mutation in the SLC5A2 gene and without impaired glucose tolerance and type 1 or 2 diabetes mellitus.
Other: Mixed-meal-tolerance-test
To assess the dynamics of the glucagon-incretin axis we need to perform the MMTT. Thereby the patients need to consume a body weight adjusted, standardized meal and we draw blood at fixed time points over 4 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in the glucagon-incretin axis.
Time Frame: 18 months

Glucose tolerance will be assessed by using the 4 hours area under the curve (AUC) for glucose.

Beta-cell function will be assessed by the 4h-AUC's for insulin, c-peptide and the 4h-AUC insulin:glucose ratio will be calculated and compared. The calculation of the alpha-cell function will be performed with the AUC of glucagon and the AUC glucagon/glucose ratio. GIP, GLP-1 and GLP-2 will be determined using the AUC. The AUC's will be calculated by the trapezoidal method
18 months
Changes in the gene expression
Time Frame: 18 months
By collecting blood samples for gene expression analysis before and after the test and comparing it to our healthy controls.
18 months

Collaborators and Investigators

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

Sponsor

Medical University Innsbruck

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

January 24, 2019

Primary Completion (ANTICIPATED)

January 1, 2021

Study Completion (ANTICIPATED)

January 1, 2022

Study Registration Dates

First Submitted

May 23, 2019

First Submitted That Met QC Criteria

May 23, 2019

First Posted (ACTUAL)

May 28, 2019

Study Record Updates

Last Update Posted (ACTUAL)

May 29, 2019

Last Update Submitted That Met QC Criteria

May 27, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20190121-1930

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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 Cardiovascular Diseases

Clinical Trials on Mixed-meal-tolerance-test

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Myanmar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe