Plain English Summary
Background and study aims:
Glycogen storage disease type 1 (GSD1) is an inherited disorder caused by a problem with an enzyme called glucose-6-phosphatase, which is responsible for the breakdown of stored sugar (glycogen) in the body's cells into sugar (glucose) that can be used for energy. This causes glycogen to build up in the body's tissues, stopping vital organs from functioning properly and lowering blood sugar levels (hypoglycaemia). In GSD1, increased activity of the enzyme biotinidase is often observed, and this enzyme may serve as a biomarker (natural chemical indicator) for GSD1. Biotinidase is an enzyme allows the body to use and to recycle the B vitamin biotin, which interacts with enzymes that digest carbohydrates, fats and amino acids (protein building blocks). It is possible that a higher demand of biotin in GSD1 may lead to increased biotinidase activity. One reason for this may be increased fat production. The primary aim of this study is to explore the metabolic (breakdown) factors determining biotinidase activity as a biomarker in GSD1. Secondly, early data show that GSD1 patients have increased concentrations of an abnormal type of lipid (fat) called deoxysphingolipids (deoxySL). In another inherited disease primarily affecting deoxysphingolipid production, high deoxysphingolipids levels cause an inherited axonal neuropathy (a disorder that affects the way nerves carry signals). This study will also explore the value of deoxysphingolipids as new biomarkers in GSD1, and examine patients for the presence of related nervous system problems (neuropathy). In addition, the role of biotinidase activity and deoxysphingolipids will also be studied in patients with other disorders of lipid (fat) and carbohydrate metabolism (breakdown).
Who can participate?
Patients aged 16 years and over who have GSD1 or other disorders of lipid and carbohydrate metabolism, and healthy volunteers of the same age.
What does the study involve?
For GSD1 patients, blood samples for scientific analyses are collected repeatedly as part of routine medical care (GSD1 patients) over the course of two years. One measurement of nerve conduction velocity by electroneurography is also performed. This involves stimulating specific nerves using electricity to find out how well the signal travels along them. For patients with other disorders of lipid and carbohydrate metabolism, blood samples are collected at two regular outpatient appointments. For healthy participants, the study includes a single blood draw at the start of the study.
What are the possible benefits and risks of participating?
At this time, there is no direct benefit for study participants. However, this study will broaden our knowledge about metabolic disturbances in glycogen storage disease type 1, and the value and utility of novel biomarkers are explored. This may help to optimize monitoring and treatment of the disease in future. As there is no study specific intervention, there is no specific risk of participating in this study.
Where is the study run from?
University Hospital Zurich (Switzerland)
When is study starting and how long is it expected to run for?
April 2014 to October 2017
Who is funding the study?
University of Zurich, Clinical Research Priority Program (CRPP) radiz - Rare Disease Initiative Zurich (Switzerland)
Who is the main contact?
Dr Michel Hochuli
michel.hochuli@usz.ch
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
KEK-ZH Nr. 2013-0632
Study information
Scientific title
The role of biotinidase activity and deoxy-sphingolipids in glycogen storage disease type 1 and other disorders of carbohydrate and lipid metabolism
Acronym
Study hypothesis
The aim of this study is to evaluate the pathophysiological background and clinical utility of two biomarkers (biotinidase activity and deoxy-Sphingolipids) in glycogen storage disease type 1.
Ethics approval
Ethics Committee Zurich, 07/05/2014, ref: 2013-0632
Study design
Mono-centric epidemiological observational cohort study
Primary study design
Observational
Secondary study design
Cohort study
Trial setting
Hospitals
Trial type
Other
Patient information sheet
No participant information sheet available
Condition
Glycogen storage disease type 1
Intervention
GSD1 patients: The total duration of observation after enrolment is two years. Usual medical and dietary treatment is continued during the study (no study specific treatment intervention). Blood samples for analysis of study specific laboratory tests (biotinidase activity, plasma fatty acid profiles, sphingolipid profiles, metabolite profiles) are collected at each regular consultation during the study period (usually every 4-6 months). A single measurement of nerve conduction (electroneurography) is performed any time during the observation period.
Patients with hypertriglyceridemia, Diabetes mellitus or NAFLD: Blood samples for the study specific laboratory tests are collected on the occasion of two regular outpatient consultations during 12 months.
Healthy controls: A single blood sample is collected at time of enrolment.
Intervention type
Other
Phase
Drug names
Primary outcome measure
1. Biotinidase activity in plasma is measured using a standardized colorimetric assay at the time of each regular consultation during the study period (usually every 4-6 months) for patients and at the time of enrollment for healthy controls
2. Concentration of deoxy-Sphingolipids in plasma is measured using GC-MS at the time of each regular consultation during the study period (usually every 4-6 months) for patients and at the time of enrollment for healthy controls
Secondary outcome measures
Motor and sensory nerve conduction velocity is measured using electroneurography (ENG), one single any time during the observation period (only GSD1 patients).
Overall trial start date
01/04/2014
Overall trial end date
31/10/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Patients:
1. Over 16 years of age)
2. Signed informed consent
3. Diagnosis of Glycogen storage disease type 1, hypertriglyceridemia, diabetes mellitus or non-alcoholic fatty liver disease (NAFLD)
Healthy controls:
1. Male or female aged 18 years and over
2. Healthy, no chronic disease, no intercurrent disease at time of examination/blood draw, normal weight (BMI 19-25 kg/m2), no excessive alcohol consumption
3. Signed informed consent
Participant type
Mixed
Age group
Adult
Gender
Both
Target number of participants
At least 10 GSD1 patients. 30 healthy controls
Participant exclusion criteria
Patients:
1. Contraindications on ethical grounds
2. Hepatocellular carcinoma (GSD1)
3. Women who are pregnant or breast feeding
Health Controls:
Any relevant chronic or intercurrent disease at the time of examination.
Recruitment start date
01/04/2014
Recruitment end date
01/10/2017
Locations
Countries of recruitment
Switzerland
Trial participating centre
University Hospital Zurich
Department of Endocrinology, Diabetes and Clinical Nutrition
Raemistrasse 100
Zurich
CH-8091
Switzerland
Funders
Funder type
University/education
Funder name
University of Zurich, Clinical Research Priority Program (CRPP) radiz - Rare Disease Initiative Zurich
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal, with intent to publish around one year after your overall trial end date.
Intention to publish date
31/10/2017
Participant level data
Not expected to be available
Basic results (scientific)
Publication list
2018 results in https://www.ncbi.nlm.nih.gov/pubmed/30037504