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Trial registered on ANZCTR


Registration number
ACTRN12617001111369
Ethics application status
Approved
Date submitted
21/07/2017
Date registered
28/07/2017
Date last updated
28/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
An investigation into heterozygosity for glycogen storage disease as a possible cause of glycogenic hepatopathy in type 1 diabetes
Scientific title
An investigation into heterozygosity for glycogen storage disease as a possible cause of glycogenic hepatopathy in type 1 diabetes
Secondary ID [1] 292490 0
None
Universal Trial Number (UTN)
U1111-1199-6662
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 304123 0
Glycogenic hepatopathy 304124 0
Glycogen storage disease 304125 0
Condition category
Condition code
Metabolic and Endocrine 303453 303453 0 0
Diabetes
Metabolic and Endocrine 303454 303454 0 0
Metabolic disorders
Oral and Gastrointestinal 303455 303455 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Blood sample taken at enrolment for gene panel for glycogen storage diseases, to determine whether there is an association between glycogen storage disease and glycogenic hepatopathy in a population with type 1 diabetes. Trial follow up will only be to inform patients the result of gene testing. Patients will receive ongoing clinical follow up for their glycogenic hepatopathy and type 1 diabetes irrespective of results of gene studies.
Intervention code [1] 298670 0
Diagnosis / Prognosis
Intervention code [2] 298700 0
Early detection / Screening
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302826 0
Presence of heterozygosity for glycogen storage disease per gene panel testing on a blood sample.
Timepoint [1] 302826 0
At enrolment
Secondary outcome [1] 337171 0
HbA1c
Timepoint [1] 337171 0
At enrolment into study
Secondary outcome [2] 337172 0
Serum lactate
Timepoint [2] 337172 0
At enrolment into study

Eligibility
Key inclusion criteria
Inclusion criteria:
• Type 1 diabetes
• Glycogenic hepatopathy either:
• Identified on liver biopsy (pathologic overloading of hepatocytes with glycogen) or
• Suspected clinically based on hepatomegaly on hepatic imaging, plus transaminases elevated greater than two times the upper limit of normal, plus elevated serum lactate persistent for more than 1 week

Minimum age
8 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Another known cause of chronic liver disease
• Elevated transaminases attributable to another cause
• Do not consent to participate, or parent does not consent to participate in the case of a legal minor.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
This is a pilot study recruiting approximately 10 patients from the Mater and LCCH. Pathogenic variants for GSDs are well defined. If all the forms of GSD are combined, GSD frequency is estimated to occur in the general population at a frequency of less than 1:10000. This corresponds to a carrier frequency of less than 1:50. A likely pathogenic mutation predicts 95-99.9% chance that the mutation is causative. Thus there is a 20% chance that a pathogenic mutation would occur by chance in one of our ten patients. Thus far the literature on type 1 diabetes and carrier status for GSD presenting with glycogenic hepatopathy consists of a single case. 10 cases will add substantially to current knowledge, and will aid in guiding further research.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 16684 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 297058 0
Charities/Societies/Foundations
Name [1] 297058 0
Mater Foundation
Address [1] 297058 0
Mater Hospital, Raymond Terrace, South Brisbane, Qld, Australia 4101
Country [1] 297058 0
Australia
Primary sponsor type
Individual
Name
Dr Stephanie Teasdale
Address
Queensland Diabetes and Endocrine Centre, Level 2 Annerley Road Campus, Annerley Road, Mater Hospital, South Brisbane, Qld 4101
Country
Australia
Secondary sponsor category [1] 296063 0
Hospital
Name [1] 296063 0
Mater Hospital
Address [1] 296063 0
Mater Hospital, Raymond Terrace, South Brisbane, Qld, Australia 4101
Country [1] 296063 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298242 0
Mater Misericordiae Ltd Human Research Ethics Committee (EC00332)
Ethics committee address [1] 298242 0
Human Research Ethics Committee, Mater Research Level 2 Aubigny Place, Raymond Terrace, South Brisbane 4101
Ethics committee country [1] 298242 0
Australia
Date submitted for ethics approval [1] 298242 0
06/02/2017
Approval date [1] 298242 0
13/07/2017
Ethics approval number [1] 298242 0

Summary
Brief summary
Glycogenic hepatopathy is an uncommon condition causing painful liver enlargement, impaired liver function and in the long term, may cause irreversible liver fibrosis in young individuals with type 1 diabetes. We wish to study whether there may be an underlying genetic cause which increases the risk for people to develop this condition.
Glycogenic hepatopathy is thought to occur when there are concomitant high blood glucose levels and elevated insulin levels, and may be associated with elevated serum lactate levels. This triad contributes to increased liver glycogen storage ultimately culminating in liver damage.
Excess hepatic glycogen storage is also characterstic of glycogen storage diseases, which are a group of heritable conditions where storage of glucose or release of glucose from storage does not occur normally, and can cause enlargement of the liver similar to glycogenic hepatopathy. People who have glycogen storage diseases typically have a mutation (change) in both copies of the causative gene. However, we are addressing the question of whether having type 1 diabetes with only one copy of the mutation for glycogen storage diseases (heterozygosity) is sufficient to precipitate abnormal glucose storage or release, resulting in the development of glycogenic hepatopathy. In support of our hypothesis, strict blood glucose control reverses glycogenic hepatopathy.
This pilot study will help clarify whether genetic sequencing for mutations which cause glycogen storage disorders can identify young people with type 1 diabetes at risk of glycogenic hepatopathy. This will enable us to alter clinical practice by facilitating genetic counselling of these patients on the particular importance of tight blood glucose control in their case and make diagnosis of this disorder less invasive. Indeed, currently, a definitive diagnosis of glycogenic hepatopathy can only be made by liver biopsy. This may be hazardous particularly in young children, a common time when the disorder first presents. Determining whether there is a genetic mutation associated with glycogenic hepatopathy may enable diagnosis to be made without having to perform a liver biopsy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76450 0
Dr Stephanie Teasdale
Address 76450 0
Queensland Diabetes and Endocrine Centre, Level 2 Annerley Road Campus, Mater Hospital, Annerley Road, South Brisbane, Qld 4101
Country 76450 0
Australia
Phone 76450 0
+61 7 31638111
Fax 76450 0
Email 76450 0
stephanie.teasdale@mater.org.au
Contact person for public queries
Name 76451 0
Dr Stephanie Teasdale
Address 76451 0
Queensland Diabetes and Endocrine Centre, Annerley Road Campus, Mater Hospital, Annerley Road, South Brisbane, Qld 4101
Country 76451 0
Australia
Phone 76451 0
+61 7 31638111
Fax 76451 0
Email 76451 0
stephanie.teasdale@mater.org.au
Contact person for scientific queries
Name 76452 0
Dr Stephanie Teasdale
Address 76452 0
Queensland Diabetes and Endocrine Centre, Level 2 Annerley Road Campus, Mater Hospital, Annerley Road, South Brisbane, Qld 4101
Country 76452 0
Australia
Phone 76452 0
+61 7 31638111
Fax 76452 0
Email 76452 0
stephanie.teasdale@mater.org.au

No data has been provided for results reporting
Summary results
Not applicable