Glycosylation in Patients With Galactosaemia

NCT02218632 | Completed

• 2 other identifiers: 12020grant PAC number 12.64
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Classical Galactosaemia

Keywords

Galactosaemia; Dysglycosylation; Diet

Outcome Measures

Primary Outcomes (1)

• 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

  2 years

Secondary Outcomes (1)

• Number of participants with Classical Galactosaemia with variations in their glycosylation status in the Irish cohort

  2 years

Study Arms (2)

lactose-free diet

ACTIVE COMPARATOR

lactose-free diet (standard therapy) vs. lactose-free diet plus temporary oral galactose supplements

Other: lactose-free diet

lactose free diet

ACTIVE COMPARATOR

lactose-free diet (standard therapy)

Dietary Supplement: Temporary oral galactose supplements

Interventions

lactose-free diet OTHER

standard diet

Also known as: On established lactose-free diet

lactose-free diet

Temporary oral galactose supplements DIETARY_SUPPLEMENT

galactose supplements in the range of physiological galactose production

Also known as: In addition to lactose-free diet

lactose free diet

Eligibility Criteria

• Age: 5 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's University Hospital, Ireland: lead
• Health Research Board, Ireland: collaborator
• Medical Research Charities Group Ireland: collaborator
• University College Dublin: collaborator

Study Sites (1)

National Centre for Inherited Metabolic Disorders, Children's University Hospital, Temple Street

Dublin, 1, Ireland

Location

Related Publications (2)

• 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.

  PMID: 24359113 RESULT

• Knerr 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.

  PMID: 23430559 RESULT

MeSH Terms

Conditions

Galactosemias

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Carbohydrate Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Eileen Treacy, MD, Prof

  University Children's Hospital Dublin Irleland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2014
• First Posted: August 18, 2014
• Study Start: July 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: August 18, 2014

Record last verified: 2014-08

Locations

IE (1)