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

Congenital Heart Diseases Clinical Trial

— (CARDIoG)  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02503267
• Other study ID #: CARDIoG
• Status: Recruiting
• Phase: N/A
• First received: July 13, 2015
• Last updated: March 24, 2017
• Start date: July 2015
• Est. completion date: June 2017

Study information

• Verified date: March 2017
• Source: Hospital Universitari Vall d'Hebron Research Institute
• Contact: Berta Miranda, MD
• Phone: +34934894038
• Email: bmiranda[@]vhebron.net
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Antithrombin III Deficiency
• Congenital Disorder of Glycosylation
• Congenital Disorders of Glycosylation
• Congenital Heart Diseases
• Conotruncal Defects
• Disease
• Heart Defects, Congenital
• Heart Diseases
• Heart Septal Defects

Intervention

Other:
• none intervention

Locations

Country	Name	City	State
Spain	Vall d'Hebron Hospital	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Universitari Vall d'Hebron Research Institute	Universidad de Murcia

Country where clinical trial is conducted

Spain, 

References & Publications (9)

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. Erratum in: PLoS One. 2015;10(3):e0122177. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. Erratum in: Trends Biochem Sci. 2006 May;31(5):251. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Genetical alteractions of disorders of glycosylation		1 year
Other	Association between disorders of glycosylation and thromboembolic events		1 year
Primary	Disorders of glycosylation		1 year
Secondary	Incidence of antithrombin deficiency		1 year