ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

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]

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

Glycogenic hepatopathy

Glycogen storage disease

Condition category

Condition code

Metabolic and Endocrine

Diabetes

Metabolic and Endocrine

Metabolic disorders

Oral and Gastrointestinal

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]

Diagnosis / Prognosis

Intervention code [2]

Early detection / Screening

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Presence of heterozygosity for glycogen storage disease per gene panel testing on a blood sample.

Timepoint [1]

At enrolment

Secondary outcome [1]

HbA1c

Timepoint [1]

At enrolment into study

Secondary outcome [2]

Serum lactate

Timepoint [2]

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

Sex

Both males and females

Can healthy volunteers participate?

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

14/08/2017

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]

4101 - South Brisbane

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Mater Foundation

Address [1]

Mater Hospital, Raymond Terrace, South Brisbane, Qld, Australia 4101

Country [1]

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]

Hospital

Name [1]

Mater Hospital

Address [1]

Mater Hospital, Raymond Terrace, South Brisbane, Qld, Australia 4101

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Mater Misericordiae Ltd Human Research Ethics Committee (EC00332)

Ethics committee address [1]

Human Research Ethics Committee, Mater Research Level 2 Aubigny Place, Raymond Terrace, South Brisbane 4101

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

06/02/2017

Approval date [1]

13/07/2017

Ethics approval number [1]

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

Dr Stephanie Teasdale

Address

Queensland Diabetes and Endocrine Centre, Level 2 Annerley Road Campus, Mater Hospital, Annerley Road, South Brisbane, Qld 4101

Country

Australia

Phone

+61 7 31638111

Fax

stephanie.teasdale@mater.org.au

Contact person for public queries

Name

Stephanie Teasdale

Address

Queensland Diabetes and Endocrine Centre, Annerley Road Campus, Mater Hospital, Annerley Road, South Brisbane, Qld 4101

Country

Australia

Phone

+61 7 31638111

Fax

stephanie.teasdale@mater.org.au

Contact person for scientific queries

Name

Stephanie Teasdale

Address

Queensland Diabetes and Endocrine Centre, Level 2 Annerley Road Campus, Mater Hospital, Annerley Road, South Brisbane, Qld 4101

Country

Australia

Phone

+61 7 31638111

Fax

stephanie.teasdale@mater.org.au

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically