Endogenous Glucose Production in Patients With Glycogen Storage Disease Type Ia

Glycogen Storage Disease Type IA Clinical Trial

— ENGLUPRO GSDIa  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04311307
• Other study ID #: NL73191.042.20
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 19, 2021
• Est. completion date: February 7, 2022

Study information

• Verified date: February 2022
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 7, 2022
• Est. primary completion date: February 7, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glycogen Storage Disease
• Glycogen Storage Disease Type I
• Glycogen Storage Disease Type IA
• Metabolic Diseases

Intervention

Biological:
• [6,6-2H2]glucose
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.

Locations

Country	Name	City	State
Netherlands	University of Groningen, UMC Groningen	Groningen

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	Ultragenyx Pharmaceutical Inc

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	[6,6-2H2]glucose concentration in GSDIa patients	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	[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
Secondary	[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
Secondary	[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
Secondary	[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
Secondary	[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
Secondary	[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