"Incidence and Consequences of Disorders of Glycosylation in Patients With Conotruncal and Septal Heart Defects" ((CARDIoG))

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ClinicalTrials.gov Identifier: NCT02503267

Recruitment Status : Unknown

Verified March 2017 by Hospital Universitari Vall d'Hebron Research Institute.
Recruitment status was: Recruiting

First Posted : July 20, 2015

Last Update Posted : March 27, 2017

Sponsor:

Collaborator:

Universidad de Murcia

Information provided by (Responsible Party):

Hospital Universitari Vall d'Hebron Research Institute

Study Description

Brief Summary:

The objective of the study is to investigate congenital disorders of glycosylation in congenital heart diseases without a clear molecular or genetic basis.

Condition or disease	Intervention/treatment
Congenital Heart Diseases Conotruncal Defects Congenital Disorder of Glycosylation Antithrombin III Deficiency	Other: none intervention

Detailed Description:

Congenital disorders of glycosylation (CDG) are a family of inherited disorders caused by defects in the synthesis of glycans, glycoproteins or other glycoconjugates. Congenital disorders of glycosylation (CDG) are a family of inherited disorders caused by defects in the synthesis of glycans, glycoproteins or other glycoconjugates. Glycosylation of proteins is crucial for a proper organ morphogenesis and for an appropriate coagulation system functioning. The neurological system is commonly affected in this type of disorders but cases of CDG with normal neurological development have been recently described. The group of Experimental Hematology and Clinic Oncology of the University of Murcia (Spain) recently described a rare disorder of glycosylation (ALG12-CDG) as the cause of antithrombin deficiency in a patient of 19 years with a history of repaired ventricular septal defect.

On the other hand, population studies have shown an increased incidence of thromboembolic events in patients with congenital heart disease when compared to the general population. The identified genetic defects involved in the development of congenital heart diseases have variable or incomplete penetrance and in most cases the molecular basis is completely unknown.

The investigators postulate that a CDG might be behind the development of some forms of congenital heart disease and contribute to the greater prevalence of thromboembolic events in this patient population.

Study Design

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Study Type :	Observational
Estimated Enrollment :	300 participants
Observational Model:	Case-Only
Time Perspective:	Cross-Sectional
Official Title:	"Incidence and Consequences of Disorders of Glycosylation in Patients With Conotruncal and Septal Heart Defects" (CARDIoG)
Study Start Date :	July 2015
Estimated Primary Completion Date :	June 2017
Estimated Study Completion Date :	June 2017

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: PMM2-congenital disorder of glycosylation DOLK-congenital disorder of glycosylation Hereditary antithrombin deficiency ALG6-congenital disorder of glycosylation ALG1-congenital disorder of glycosylation COG5-congenital disorder of glycosylation ALG12-congenital disorder of glycosylation

MedlinePlus related topics: Heart Diseases

Genetic and Rare Diseases Information Center resources: Congenital Disorders of Glycosylation Hereditary Antithrombin Deficiency

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
patients with congenital heart disease patients with congenital heart disease	Other: none intervention

Outcome Measures

Primary Outcome Measures :

Disorders of glycosylation [ Time Frame: 1 year ]

Secondary Outcome Measures :

Incidence of antithrombin deficiency [ Time Frame: 1 year ]

Other Outcome Measures:

Genetical alteractions of disorders of glycosylation [ Time Frame: 1 year ]
Association between disorders of glycosylation and thromboembolic events [ Time Frame: 1 year ]

Biospecimen Retention: Samples With DNA

Through the blood sample we will:

Identify Antitrombin III deficiency
Evaluate the glycosylation degree of different glycoproteins
Do a genetic analysis

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 90 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

250-300 adult patients who are most likely to have a congenital disorder of glycosylation of proteins, such as ventricular and atrial septal defects and especially conotruncal defects

Criteria

Inclusion Criteria:

Adult with a congenital heart disease with most probability to present a congenital disorder of glycosylation of proteins

Exclusion Criteria:

Denial of informed consent.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02503267

Contacts

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Contact: Berta Miranda, MD	+34934894038 ext 4038	bmiranda@vhebron.net

Locations

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Spain
Vall d'Hebron Hospital	Recruiting
Barcelona, Spain, 08035
Contact: Berta Miranda, MD +34932743164 bmiranda@vhebron.net
Contact: Laura Dos, MD,PhD +34932743164 ldos@vhebron.net

Sponsors and Collaborators

Hospital Universitari Vall d'Hebron Research Institute

Universidad de Murcia

More Information

Publications:

Footitt EJ, Karimova A, Burch M, Yayeh T, Dupré T, Vuillaumier-Barrot S, Chantret I, Moore SE, Seta N, Grunewald S. Cardiomyopathy in the congenital disorders of glycosylation (CDG): a case of late presentation and literature review. J Inherit Metab Dis. 2009 Dec;32 Suppl 1:S313-9. doi: 10.1007/s10545-009-1262-1. Epub 2009 Sep 7. Review.

Gehrmann J, Sohlbach K, Linnebank M, Böhles HJ, Buderus S, Kehl HG, Vogt J, Harms E, Marquardt T. Cardiomyopathy in congenital disorders of glycosylation. Cardiol Young. 2003 Aug;13(4):345-51. Review.

Romano S, Bajolle F, Valayannopoulos V, Lyonnet S, Colomb V, de Baracé C, Vouhe P, Pouard P, Vuillaumier-Barrot S, Dupré T, de Keyzer Y, Sidi D, Seta N, Bonnet D, de Lonlay P. Conotruncal heart defects in three patients with congenital disorder of glycosylation type Ia (CDG Ia). J Med Genet. 2009 Apr;46(4):287-8. doi: 10.1136/jmg.2008.057620.

Mitra N, Sinha S, Ramya TN, Surolia A. N-linked oligosaccharides as outfitters for glycoprotein folding, form and function. Trends Biochem Sci. 2006 Mar;31(3):156-63. Epub 2006 Feb 10. Review. Erratum in: Trends Biochem Sci. 2006 May;31(5):251.

Lin YS, Liu PH, Wu LS, Chen YM, Chang CJ, Chu PH. Major adverse cardiovascular events in adult congenital heart disease: a population-based follow-up study from Taiwan. BMC Cardiovasc Disord. 2014 Mar 21;14:38. doi: 10.1186/1471-2261-14-38.

de la Morena-Barrio ME, Hernández-Caselles T, Corral J, García-López R, Martínez-Martínez I, Pérez-Dueñas B, Altisent C, Sevivas T, Kristensen SR, Guillén-Navarro E, Miñano A, Vicente V, Jaeken J, Lozano ML. GPI-anchor and GPI-anchored protein expression in PMM2-CDG patients. Orphanet J Rare Dis. 2013 Oct 20;8:170. doi: 10.1186/1750-1172-8-170.

Martínez-Martínez I, Ordóñez A, Navarro-Fernández J, Pérez-Lara A, Gutiérrez-Gallego R, Giraldo R, Martínez C, Llop E, Vicente V, Corral J. Antithrombin Murcia (K241E) causing antithrombin deficiency: a possible role for altered glycosylation. Haematologica. 2010 Aug;95(8):1358-65. doi: 10.3324/haematol.2009.015487. Epub 2010 Apr 30.

Aguila S, Martínez-Martínez I, Dichiara G, Gutiérrez-Gallego R, Navarro-Fernández J, Vicente V, Corral J. Increased N-glycosylation efficiency by generation of an aromatic sequon on N135 of antithrombin. PLoS One. 2014 Dec 8;9(12):e114454. doi: 10.1371/journal.pone.0114454. eCollection 2014. Erratum in: PLoS One. 2015;10(3):e0122177.

Dorn C, Grunert M, Sperling SR. Application of high-throughput sequencing for studying genomic variations in congenital heart disease. Brief Funct Genomics. 2014 Jan;13(1):51-65. doi: 10.1093/bfgp/elt040. Epub 2013 Oct 3. Review.

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Responsible Party:	Hospital Universitari Vall d'Hebron Research Institute
ClinicalTrials.gov Identifier:	NCT02503267
Other Study ID Numbers:	CARDIoG
First Posted:	July 20, 2015 Key Record Dates
Last Update Posted:	March 27, 2017
Last Verified:	March 2017

Keywords provided by Hospital Universitari Vall d'Hebron Research Institute:


antithrombin III deficiency congenital heart diseases

Additional relevant MeSH terms:

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Heart Diseases Heart Septal Defects Antithrombin III Deficiency Congenital Disorders of Glycosylation Cardiovascular Diseases Heart Defects, Congenital Cardiovascular Abnormalities Congenital Abnormalities Carbohydrate Metabolism, Inborn Errors	Metabolism, Inborn Errors Genetic Diseases, Inborn Metabolic Diseases Blood Coagulation Disorders, Inherited Blood Coagulation Disorders Hematologic Diseases Blood Protein Disorders Thrombophilia

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