Endogenous Glucose Production in Patients With Glycogen Storage Disease Type Ia (ENGLUPRO GSDIa)

February 10, 2022 updated by: Terry G.J. Derks, MD, PhD, University Medical Center Groningen

Endogenous Glucose Production in Subjects With Glycogen Storage Disease Type Ia Estimated by a Single Oral Dose of Stable Isotopes: an Investigator-initiated Human Pilot Study

Glycogen storage disease type Ia (GSDIa) subjects retain a limited capacity for endogenous glucose production (EGP). To date, the origin of residual EGP in GSDIa patients is unknown. Either increased glycogen debranching or lysosomal glycogen breakdown can account for residual EGP in GSDIa.

Innovative treatments for GSDIa (e.g. AAV8-mediated gene therapy and mRNA therapy) are being developed.Therefore, longitudinal minimally-invasive monitoring of outcomes after therapeutic interventions in GSD Ia subjects becomes warranted.

The primary objective is to test the feasibility of EGP quantification in adult GSDIa subjects by stable isotopes after a single oral [6,6-2H2]glucose dose. Secondary objectives are to compare EGP assessed by a single oral [6,6-2H2]glucose dose (a) in GSDIa patients versus matched healthy participants, (b) among GSDIa patients, (c) in the pre-prandial state versus the fed state, (d) in the controlled hospital setting versus the home setting. Data collected from the continuous glucose monitoring data will also be compared

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

Study design: An investigator-initiated human pilot-study. Study population: Ten adult subjects with GSDIa and ten age and gender-matched healthy subjects.

Interventions: Three experiments will be performed for each subject. During the first in hospital experiment, two oral D-[6,6-2H2]glucose loads will be performed 2 hours before breakfast and at lunchtime, respectively. The third oral D-[6,6-2H2]glucose load will be performed at home (random time). Capillary blood samples will be collected on filter paper at specific time points after each oral D-[6,6-2H2]glucose load. During the experiments, subjects will be monitored by subcutaneous continuous glucose monitoring (CGM).

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2
  • Phase 1

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

      • Groningen, Netherlands
        • University of Groningen, UMC Groningen

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

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • The diagnosis should be confirmed by G6PC mutation analysis
  • Age above 16 years
  • Stable medical condition before the start of the test procedures

Exclusion Criteria:

  • Age < 16 years
  • Intercurrent illness
  • Recent history of hospitalization due to hypoglycemia
  • Pregnancy
  • History suggestive of diabetes or fasting intolerance
  • First grade family member with a confirmed diagnosis associated with fasting intolerance

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: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patients
GSDIa patients
Each subject will be administered two oral [6,6-2H2]glucose loads (pre-prandial, fed) in the hospital setting and one oral [6,6-2H2]glucose load at home setting (random time). Capillary blood samples will be collected on filter paper 10 times at specific time points after each oral [6,6-2H2]glucose load.
Active Comparator: Controls
Healthy volunteers
Each subject will be administered two oral [6,6-2H2]glucose loads (pre-prandial, fed) in the hospital setting and one oral [6,6-2H2]glucose load at home setting (random time). Capillary blood samples will be collected on filter paper 10 times at specific time points after each oral [6,6-2H2]glucose load.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
[6,6-2H2]glucose concentration in GSDIa patients
Time Frame: every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load
Endogenous glucose production (EGP) in GSDIa will be assessed through minimal model calculation
every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load

Secondary Outcome Measures

Outcome Measure
Time Frame
[6,6-2H2]glucose concentration in GSDIa patients and matched healthy participants
Time Frame: every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load
every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load
[6,6-2H2]glucose concentration in severe and attenuated GSDIa patients
Time Frame: every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load
every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load
[6,6-2H2]glucose concentration in the pre-prandial state versus the fed state in GSDIa patients
Time Frame: every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load
every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load
[6,6-2H2]glucose concentration in the pre-prandial state versus the fed state in healthy participants
Time Frame: every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load
every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load
[6,6-2H2]glucose concentration in the controlled hospital setting versus the home setting in GSDIa patients
Time Frame: every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load
every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load
[6,6-2H2]glucose concentration in the controlled hospital setting versus the home setting in healthy participants
Time Frame: every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load
every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load

Collaborators and Investigators

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

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.

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 19, 2021

Primary Completion (Actual)

February 7, 2022

Study Completion (Actual)

February 7, 2022

Study Registration Dates

First Submitted

February 25, 2020

First Submitted That Met QC Criteria

March 12, 2020

First Posted (Actual)

March 17, 2020

Study Record Updates

Last Update Posted (Actual)

February 11, 2022

Last Update Submitted That Met QC Criteria

February 10, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

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.

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