Endogenous Glucose Production in Patients With Glycogen Storage Disease Type Ia

NCT04311307 | Completed Phase 1

• 1 other identifier: NL73191.042.20
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Glycogen Storage Disease Type IA

Outcome Measures

Primary Outcomes (1)

• [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 Outcomes (6)

• [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 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

• [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

Study Arms (2)

Patients

EXPERIMENTAL

GSDIa patients

Biological: [6,6-2H2]glucose

Controls

ACTIVE COMPARATOR

Healthy volunteers

Biological: [6,6-2H2]glucose

Interventions

[6,6-2H2]glucose BIOLOGICAL

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.

Controls; Patients

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Ultragenyx Pharmaceutical Inc: collaborator

Study Sites (1)

University of Groningen, UMC Groningen

Groningen, Netherlands

Location

Related Publications (1)

• Rossi A, Venema A, Haarsma P, Feldbrugge L, Burghard R, Rodriguez-Buritica D, Parenti G, Oosterveer MH, Derks TGJ. A Prospective Study on Continuous Glucose Monitoring in Glycogen Storage Disease Type Ia: Toward Glycemic Targets. J Clin Endocrinol Metab. 2022 Aug 18;107(9):e3612-e3623. doi: 10.1210/clinem/dgac411.

  PMID: 35786777 DERIVED

MeSH Terms

Conditions

Hepatorenal form of glycogen storage disease

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 25, 2020
• First Posted: March 17, 2020
• Study Start: January 19, 2021
• Primary Completion: February 7, 2022
• Study Completion: February 7, 2022
• Last Updated: February 11, 2022

Record last verified: 2022-02

Locations

NL (1)