Endogenous Glucose Production in Patients With Glycogen Storage Disease Type Ia

Phase 1

Completed

• Conditions: Glycogen Storage Disease Type IA
• Interventions: Biological: [6,6-2H2]glucose

• Registration Number: NCT04311307
• Lead Sponsor: University Medical Center Groningen

Brief Summary

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

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 Timeline

• Study First Submitted: 2020-02-25
• Study First Submitted QC: 2020-03-12
• Study First Posted: 2020-03-17
• Study Start: 2021-01-19
• Status Verified: 2022-02
• Primary Completion: 2022-02-07
• Study Completion: 2022-02-07
• Last Update Submitted: 2022-02-10
• Last Update Posted: 2022-02-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients	[6,6-2H2]glucose	GSDIa patients
Controls	[6,6-2H2]glucose	Healthy volunteers

Primary Outcome Measures

Name	Time	Method
[6,6-2H2]glucose concentration in GSDIa patients	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

Secondary Outcome Measures

Name	Time	Method
[6,6-2H2]glucose concentration in the controlled hospital setting versus the home setting in healthy participants	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 GSDIa patients and matched healthy participants	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	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	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	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	every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load

Trial Locations

Locations (1)

University of Groningen, UMC Groningen; 🇳🇱 Groningen, Netherlands