Classical GalactosaemiaNCT02218632
Glycosylation in Patients With Galactosaemia
A study testing lactose-free diet and Temporary oral galactose supplements in people with Classical Galactosaemia, run by Children's University Hospital, Ireland at 1 site in Ireland.
Trial summary
Galactosaemia is an inherited condition caused by a lack of an enzyme (catalyst) which normally breaks down galactose (the sugar found in milk products). This affects 1:19,000 births annually in Ireland (the highest incidence worldwide) and is screened for by the National Newborn Screening Programme. Read more about this study
- Who is it for?
- Ages 5 to 40 years
- Conditions the study is for
- Classical Galactosaemia
- What is being tested?
- lactose-free diet and Temporary oral galactose supplements
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteIreland
- Study dates
- Jul 2012to Aug 2014
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Classical galactosaemia
- Q188R Genotype
- On lactose-free diet
- No complications, condition well controlled
- Male/femal adults and children aged between 5-12 yrs.
- Informed consent /assent
- Patient attend the Galactosaemia Clinic, NCIMD Dublin
Who cannot join
- Complications, such as cataracts
- Galactosaemia varaint, no Q188R-Genotype
- Poor compliance
- Intercurrent illness
- Individual may not complete follow up
- Children below 5 years of age
- Unable to provide informed consent
- Patient not under the care of Galactosaemia Clinic, NCIMD Dublin
Trial locations and contacts
1 site in 1 country.
Ireland1 site
National Centre for Inherited Metabolic Disorders, Children's University Hospital, Temple Street
Dublin, 1
About this study
Official title: Galactosaemia, a Modifiable Multi-system Glycosylation Disorder?
Galactosaemia is an inherited condition caused by a lack of an enzyme (catalyst) which normally breaks down galactose (the sugar found in milk products). This affects 1:19,000 births annually in Ireland (the highest incidence worldwide) and is screened for by the National Newborn Screening Programme. When an affected infant is diagnosed, galactose is immediately restricted from the diet. This prevents often fatal liver disease and other immediate complications. However, despite early treatment the majority of affected patients go on to develop long-term complications such as intellectual impairment, neurological complications, speech difficulties and infertility in females. The underlying mechanisms for these complications are unclear. The investigators have shown in detailed biochemical and gene analysis studies that major abnormalities affecting the function of complex molecules in the body, particularly glycoproteins, (consisting of sugar chains attached to proteins) persist in treated individuals which may lead to disturbances of the body's intrinsic cellular machinery and relate to the complications seen.
In this research the investigators expand on from their earlier studies to see if they can identify biomarkers and parts of the galactose/glycosylation pathways which could be modified or changed with new treatments to improve outcomes for this condition (i.e., IgG N glycans).
In more detail, the investigators test the use of the most abundant glycoprotein in human plasma (IgG) as an improved clinical test for monitoring the galactose control needed in patients and also to see if some patients (including children aged 5-12 yrs) might have a better predicted outcome with moderate increases of galactose in the diet. The investigators believe that these studies greatly improve the understanding of Galactosaemia with a view to improving current treatment options and future outcomes.
Read the detailed description
Classical Galactosaemia is an inherited disorder of galactose metabolism caused by profound deficiency of galactose-1-phosphate uridyltransferase (GALT: EC 2.7.712). This results in a systemic accumulation of toxic galactose intermediates and a decrease in the level of UDP-galactose, a required sugar for glycosylation. Galactosaemia has a relatively high incidence in Ireland, (1:19,000 births) presenting a particular public health problem. The neonatal life-threatening phenotype (liver disease, coagulopathy and sepsis) is rescued by restriction of dietary galactose. However, outcomes of treatment are disappointing beyond the neonatal period (even after successful newborn screening, early treatment and long term compliance). The majority of Irish patients harbour the severe Q188R Galt mutation.
56.5% of Irish patients ≥ 6yrs have IQs ≤ 79; and 91.2% of Irish female patients ≥ 13yrs have Premature Ovarian Insufficiency (POI). Unfortunately, the basic pathophysiology of this condition remains enigmatic with limited treatment approaches.
In their earlier work, the investigators reported very considerable variation in patient outcomes, even among siblings. The investigators have proposed that these differences are determined by variation in galactose accessory pathways (beyond the GALT deficiency). This may result in variable galactose tolerance in patients with linked variation in glycosylation pathways which could allow for enhanced UDP-galactose bioavailability essential for glycosylation. In their previous and current work the investigators have identified ongoing dysregulation of glycoprotein formation and expression of genes involved in glycan biosynthesis and cell signalling pathways in treated Galactosaemia patients.
The present proposal, which builds on published previous work, enables the investigators to establish that Galactosaemia is a modifiable, multi-systemic glycosylation defect. The overall objectives of the work are to progress the development of biochemical markers (IgG N-glycan analysis) as prognostic indices for potentially modifiable relevant pathways. The investigators consider how the phenotype could be relaxed in some patients with Classical Galactosaemia, initially by studies of modification of exogenous galactose requirements to identify if the ongoing glycan processing defects identified may be improved reflecting accessory pathways of galactose disposal.
Study Aim: Expand previous and published work using IgG N-glycan analysis to examine the glycosylation status of treated adult Galactosaemia patients in a larger study and develop this test as a reliable diagnostic tool. The investigators also carry out a pilot study to examine the effects of diet relaxation in paediatric patients (5-12 yrs) aiming to determine optimum galactose intake levels for this cohort with the hope of preventing long-term complications later in life. The investigators propose that this research offers new insights into the ongoing pathophysiology of this rare disorder with the possibility of developing new treatment targets, which over time could be cost-effective by preventing major disability.
- Conditions
- Classical Galactosaemia
- Being tested
- lactose-free diet, Temporary oral galactose supplements
- Keywords
- Galactosaemia, Dysglycosylation, Diet
- Medical subject headings
- Galactosemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lactose-free dietOther
Also called On established lactose-free diet
standard diet
Temporary oral galactose supplementsDietary supplement
Also called In addition to lactose-free diet
galactose supplements in the range of physiological galactose production
| Study group | Role | What they receive |
|---|---|---|
| lactose-free diet | Active comparator | lactose-free diet (standard therapy) vs. lactose-free diet plus temporary oral galactose supplements Receives: Other: lactose-free diet |
| lactose free diet | Active comparator | lactose-free diet (standard therapy) Receives: Dietary Supplement: Temporary oral galactose supplements |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with Classical Galactosaemia on a lactose-free diet in Ireland with disease specific complications
clinical monitoring and biochemical assessment to determine the number of patients with classical galactsaemia in Ireland with disease specific complications
Measured: 2 years
Secondary outcomes (1)
Number of participants with Classical Galactosaemia with variations in their glycosylation status in the Irish cohort
Glycosylation analysis: IgG N-glycan analysis (serum test)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2014 (estimated)
- Study startJul 2012
- Primary completionAug 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Classical GalactosaemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's University Hospital, Ireland
- Sponsor type
- University, hospital or other
- Collaborators
- Health Research Board, Ireland, Medical Research Charities Group Ireland, University College Dublin
- Responsible party
- Sponsor
- Investigators
- Eileen Treacy, MD, Prof, Principal investigator, University Children's Hospital Dublin Irleland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02218632
- Sponsor's protocol ID
- 12020
- Other IDs
- grant PAC number 12.64
- Status last verified
- Aug 2014
- First submitted
- 7 Aug 2014
- Last updated
- 18 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Coss KP, Hawkes CP, Adamczyk B, Stockmann H, Crushell E, Saldova R, Knerr I, Rubio-Gozalbo ME, Monavari AA, Rudd PM, Treacy EP. N-glycan abnormalities in children with galactosemia. J Proteome Res. 2014 Feb 7;13(2):385-94. doi: 10.1021/pr4008305. Epub 2013 Dec 20.
PubMed 24359113Knerr I, Coss KP, Doran PP, Hughes J, Wareham N, Burling K, Treacy EP. Leptin levels in children and adults with classic galactosaemia. JIMD Rep. 2013;9:125-131. doi: 10.1007/8904_2012_191. Epub 2012 Nov 7.
PubMed 23430559
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Galactosaemia, a Modifiable Multi-system Glycosylation Disorder?
- ClinicalTrials.gov ID
- NCT02218632
- Acronym / sponsor ID
- 12020
- Conditions
- Classical Galactosaemia
- Keywords
- Galactosaemia, Dysglycosylation, Diet
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Children's University Hospital, IrelandUniversity, hospital or other
- Collaborators
- Health Research Board, Ireland, Medical Research Charities Group Ireland, University College Dublin
- Study start
- Jul 2012
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 18 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Galactosaemia is an inherited condition caused by a lack of an enzyme (catalyst) which normally breaks down galactose (the sugar found in milk products). This affects 1:19,000 births annually in Ireland (the highest incidence worldwide) and is screened for by the National Newborn Screening Programme. When an affected infant is diagnosed, galactose is immediately restricted from the diet. This prevents often fatal liver disease and other immediate complications. However, despite early treatment the majority of affected patients go on to develop long-term complications such as intellectual impairment, neurological complications, speech difficulties and infertility in females. The underlying mechanisms for these complications are unclear. The investigators have shown in detailed biochemical and gene analysis studies that major abnormalities affecting the function of complex molecules in the body, particularly glycoproteins, (consisting of sugar chains attached to proteins) persist in treated individuals which may lead to disturbances of the body's intrinsic cellular machinery and relate to the complications seen.
In this research the investigators expand on from their earlier studies to see if they can identify biomarkers and parts of the galactose/glycosylation pathways which could be modified or changed with new treatments to improve outcomes for this condition (i.e., IgG N glycans).
In more detail, the investigators test the use of the most abundant glycoprotein in human plasma (IgG) as an improved clinical test for monitoring the galactose control needed in patients and also to see if some patients (including children aged 5-12 yrs) might have a better predicted outcome with moderate increases of galactose in the diet. The investigators believe that these studies greatly improve the understanding of Galactosaemia with a view to improving current treatment options and future outcomes.
Detailed description
Classical Galactosaemia is an inherited disorder of galactose metabolism caused by profound deficiency of galactose-1-phosphate uridyltransferase (GALT: EC 2.7.712). This results in a systemic accumulation of toxic galactose intermediates and a decrease in the level of UDP-galactose, a required sugar for glycosylation. Galactosaemia has a relatively high incidence in Ireland, (1:19,000 births) presenting a particular public health problem. The neonatal life-threatening phenotype (liver disease, coagulopathy and sepsis) is rescued by restriction of dietary galactose. However, outcomes of treatment are disappointing beyond the neonatal period (even after successful newborn screening, early treatment and long term compliance). The majority of Irish patients harbour the severe Q188R Galt mutation.
56.5% of Irish patients ≥ 6yrs have IQs ≤ 79; and 91.2% of Irish female patients ≥ 13yrs have Premature Ovarian Insufficiency (POI). Unfortunately, the basic pathophysiology of this condition remains enigmatic with limited treatment approaches.
In their earlier work, the investigators reported very considerable variation in patient outcomes, even among siblings. The investigators have proposed that these differences are determined by variation in galactose accessory pathways (beyond the GALT deficiency). This may result in variable galactose tolerance in patients with linked variation in glycosylation pathways which could allow for enhanced UDP-galactose bioavailability essential for glycosylation. In their previous and current work the investigators have identified ongoing dysregulation of glycoprotein formation and expression of genes involved in glycan biosynthesis and cell signalling pathways in treated Galactosaemia patients.
The present proposal, which builds on published previous work, enables the investigators to establish that Galactosaemia is a modifiable, multi-systemic glycosylation defect. The overall objectives of the work are to progress the development of biochemical markers (IgG N-glycan analysis) as prognostic indices for potentially modifiable relevant pathways. The investigators consider how the phenotype could be relaxed in some patients with Classical Galactosaemia, initially by studies of modification of exogenous galactose requirements to identify if the ongoing glycan processing defects identified may be improved reflecting accessory pathways of galactose disposal.
Study Aim: Expand previous and published work using IgG N-glycan analysis to examine the glycosylation status of treated adult Galactosaemia patients in a larger study and develop this test as a reliable diagnostic tool. The investigators also carry out a pilot study to examine the effects of diet relaxation in paediatric patients (5-12 yrs) aiming to determine optimum galactose intake levels for this cohort with the hope of preventing long-term complications later in life. The investigators propose that this research offers new insights into the ongoing pathophysiology of this rare disorder with the possibility of developing new treatment targets, which over time could be cost-effective by preventing major disability.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| lactose-free diet | Active comparator | Other: lactose-free dietlactose-free diet (standard therapy) vs. lactose-free diet plus temporary oral galactose supplements |
| lactose free diet | Active comparator | Dietary Supplement: Temporary oral galactose supplementslactose-free diet (standard therapy) |
Who may qualify
- Ages
- 5 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Classical galactosaemia
- Q188R Genotype
- On lactose-free diet
- No complications, condition well controlled
- Male/femal adults and children aged between 5-12 yrs.
Key exclusion criteria (8 listed)
- Complications, such as cataracts
- Galactosaemia varaint, no Q188R-Genotype
- Poor compliance
- Intercurrent illness
- Individual may not complete follow up
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lactose-free dietAlso: On established lactose-free dietstandard diet | Other | lactose-free diet |
| Temporary oral galactose supplementsAlso: In addition to lactose-free dietgalactose supplements in the range of physiological galactose production | Dietary supplement | lactose free diet |
Primary outcome
Number of patients with Classical Galactosaemia on a lactose-free diet in Ireland with disease specific complications
Time frame: 2 years
clinical monitoring and biochemical assessment to determine the number of patients with classical galactsaemia in Ireland with disease specific complications
1 secondary outcome
Number of participants with Classical Galactosaemia with variations in their glycosylation status in the Irish cohort
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2014.
- Results publication: PubMed 24359113Coss KP, Hawkes CP, Adamczyk B, Stockmann H, Crushell E, Saldova R, Knerr I, Rubio-Gozalbo ME, Monavari AA, Rudd PM, Treacy EP. N-glycan abnormalities in children with galactosemia. J Proteome Res. 2014 Feb 7;13(2):385-94. doi: 10.1021/pr4008305. Epub 2013 Dec 20.
- Results publication: PubMed 23430559Knerr I, Coss KP, Doran PP, Hughes J, Wareham N, Burling K, Treacy EP. Leptin levels in children and adults with classic galactosaemia. JIMD Rep. 2013;9:125-131. doi: 10.1007/8904_2012_191. Epub 2012 Nov 7.
Related trials for Classical Galactosaemia
RecruitingObservational study
Gonadic Function and Pubertal Development in Female Patients With Classic Galactosemia
Galactosemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eileen Treacy, MD, Prof principal investigator
University Children's Hospital Dublin Irleland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing lactose-free diet and Temporary oral galactose supplements in people with Classical Galactosaemia, run by Children's University Hospital, Ireland at 1 site in Ireland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with Classical Galactosaemia on a lactose-free diet in Ireland with disease specific complications (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02218632, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2014.