Endogenous Glucose Production in Patients With Glycogen Storage Disease Type Ia

NCT ID: NCT04311307

Last Updated: 2022-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-19
• Study Completion Date: 2022-02-07

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).

Conditions

Glycogen Storage Disease Type IA

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Patients

GSDIa patients

Group Type: EXPERIMENTAL

[6,6-2H2]glucose

Intervention Type: 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

Healthy volunteers

Group Type: ACTIVE_COMPARATOR

[6,6-2H2]glucose

Intervention Type: 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.

Interventions

[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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ultragenyx Pharmaceutical Inc

INDUSTRY

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Terry G.J. Derks, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Groningen, UMC Groningen

Groningen, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 35786777 (View on PubMed)

Other Identifiers

NL73191.042.20

Identifier Type: -

Identifier Source: org_study_id