Endogenous Glucose Production in Patients With Glycogen Storage Disease Type Ia (ENGLUPRO GSDIa)
Primary Purpose
Glycogen Storage Disease Type IA
Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
[6,6-2H2]glucose
Sponsored by
About this trial
This is an interventional basic science trial for Glycogen Storage Disease Type IA
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
Sites / Locations
- University of Groningen, UMC Groningen
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Patients
Controls
Arm Description
GSDIa patients
Healthy volunteers
Outcomes
Primary Outcome Measures
[6,6-2H2]glucose concentration in GSDIa patients
Endogenous glucose production (EGP) in GSDIa will be assessed through minimal model calculation
Secondary Outcome Measures
[6,6-2H2]glucose concentration in GSDIa patients and matched healthy participants
[6,6-2H2]glucose concentration in severe and attenuated GSDIa patients
[6,6-2H2]glucose concentration in the pre-prandial state versus the fed state in GSDIa patients
[6,6-2H2]glucose concentration in the pre-prandial state versus the fed state in healthy participants
[6,6-2H2]glucose concentration in the controlled hospital setting versus the home setting in GSDIa patients
[6,6-2H2]glucose concentration in the controlled hospital setting versus the home setting in healthy participants
Full Information
NCT ID
NCT04311307
First Posted
February 25, 2020
Last Updated
February 10, 2022
Sponsor
University Medical Center Groningen
Collaborators
Ultragenyx Pharmaceutical Inc
1. Study Identification
Unique Protocol Identification Number
NCT04311307
Brief Title
Endogenous Glucose Production in Patients With Glycogen Storage Disease Type Ia
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
January 19, 2021 (Actual)
Primary Completion Date
February 7, 2022 (Actual)
Study Completion Date
February 7, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen
Collaborators
Ultragenyx Pharmaceutical Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glycogen Storage Disease Type IA
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Patients
Arm Type
Experimental
Arm Description
GSDIa patients
Arm Title
Controls
Arm Type
Active Comparator
Arm Description
Healthy volunteers
Intervention Type
Biological
Intervention Name(s)
[6,6-2H2]glucose
Intervention Description
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.
Primary Outcome Measure Information:
Title
[6,6-2H2]glucose concentration in GSDIa patients
Description
Endogenous glucose production (EGP) in GSDIa will be assessed through minimal model calculation
Time Frame
every 10 minutes within the first hour as well as 75, 90 and 120 minutes after the oral load
Secondary Outcome Measure Information:
Title
[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
Title
[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
Title
[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
Title
[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
Title
[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
Title
[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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Facility Information:
Facility Name
University of Groningen, UMC Groningen
City
Groningen
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
35786777
Citation
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.
Results Reference
derived
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Endogenous Glucose Production in Patients With Glycogen Storage Disease Type Ia
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