Erythrocyte Glutamine Level Relation to Pulmonary Hypertension Risk in Beta Thalassemia Major Children

Pulmonary Hypertension Clinical Trial

Official title:

Erythrocyte Glutamine Level Relation to Pulmonary Hypertension Risk in Beta Thalassemia Major Children in Assiut University Children Hospital

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03133169
• Other study ID #: GlnThalassemia
• Status: Completed
• Start date: June 1, 2017
• Est. completion date: August 26, 2019

Study information

• Verified date: August 2019
• Source: Assiut University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The study will investigate the relation between erythrocyte glutamine/glutamate ratio and pulmonary hypertension risk in Egyptian thalassemic children in Assiut University Children Hospital

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: August 26, 2019
• Est. primary completion date: August 25, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 18 Years

Eligibility

Inclusion Criteria:

• Established diagnosis of Thalassemia.

• PH risk documented by doppler echocardiography, defined as tricuspid regurge velocity (TRV) equal to or greater than 2.5 m/s

Exclusion Criteria:

• Acute crisis or hospitalization within 1 month of enrollment

• Hepatic dysfunction (SGPT greater than 3X normal)

• Renal dysfunction (Creatinine greater than 2X normal)

• Patients on sildenafil (Viagra), calcium channel blockers or other drugs for the control of PH.

Related Conditions & MeSH terms

• beta-Thalassemia
• Hemolysis
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension
• Thalassemia
• Thalassemia in Children

Intervention

Diagnostic Test:
• blood sample
blood sample for measuring liver and kidney function, CBC, ferritin level and erythrocyte glutamine level
• Tricuspid regurge velocity
Tricuspid regurge velocity will be measured by doppler echocardiography denoting the pulmonary hypertension risk in children

Locations

Country	Name	City	State
Egypt	Assiut University	Assiut

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

Country where clinical trial is conducted

Egypt, 

References & Publications (18)

Anthi A, Machado RF, Jison ML, Taveira-Dasilva AM, Rubin LJ, Hunter L, Hunter CJ, Coles W, Nichols J, Avila NA, Sachdev V, Chen CC, Gladwin MT. Hemodynamic and functional assessment of patients with sickle cell disease and pulmonary hypertension. Am J Respir Crit Care Med. 2007 Jun 15;175(12):1272-9. Epub 2007 Mar 22. — View Citation

De Castro LM, Jonassaint JC, Graham FL, Ashley-Koch A, Telen MJ. Pulmonary hypertension associated with sickle cell disease: clinical and laboratory endpoints and disease outcomes. Am J Hematol. 2008 Jan;83(1):19-25. — View Citation

Fung EB, Harmatz P, Milet M, Ballas SK, De Castro L, Hagar W, Owen W, Olivieri N, Smith-Whitley K, Darbari D, Wang W, Vichinsky E; Multi-Center Study of Iron Overload Research Group. Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: A report from the multi-center study of iron overload. Am J Hematol. 2007 Apr;82(4):255-65. — View Citation

Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, Brown B, Coles WA, Nichols JS, Ernst I, Hunter LA, Blackwelder WC, Schechter AN, Rodgers GP, Castro O, Ognibene FP. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004 Feb 26;350(9):886-95. — View Citation

Hebbel RP. Reconstructing sickle cell disease: a data-based analysis of the "hyperhemolysis paradigm" for pulmonary hypertension from the perspective of evidence-based medicine. Am J Hematol. 2011 Feb;86(2):123-54. doi: 10.1002/ajh.21952. Review. — View Citation

Janda S, Shahidi N, Gin K, Swiston J. Diagnostic accuracy of echocardiography for pulmonary hypertension: a systematic review and meta-analysis. Heart. 2011 Apr;97(8):612-22. doi: 10.1136/hrt.2010.212084. Epub 2011 Feb 25. Review. Erratum in: Heart. 2011 Jul;97(13):1112. — View Citation

Kuypers FA. Membrane lipid alterations in hemoglobinopathies. Hematology Am Soc Hematol Educ Program. 2007:68-73. Review. — View Citation

Machado RF, Farber HW. Pulmonary hypertension associated with chronic hemolytic anemia and other blood disorders. Clin Chest Med. 2013 Dec;34(4):739-52. doi: 10.1016/j.ccm.2013.08.006. Epub 2013 Oct 17. Review. — View Citation

Machado RF, Gladwin MT. Pulmonary hypertension in hemolytic disorders: pulmonary vascular disease: the global perspective. Chest. 2010 Jun;137(6 Suppl):30S-38S. doi: 10.1378/chest.09-3057. — View Citation

Mok E, Hankard R. Glutamine supplementation in sick children: is it beneficial? J Nutr Metab. 2011;2011:617597. doi: 10.1155/2011/617597. Epub 2011 Nov 14. — View Citation

Morris CR, Kuypers FA, Kato GJ, Lavrisha L, Larkin S, Singer T, Vichinsky EP. Hemolysis-associated pulmonary hypertension in thalassemia. Ann N Y Acad Sci. 2005;1054:481-5. — View Citation

Morris CR, Suh JH, Hagar W, Larkin S, Bland DA, Steinberg MH, Vichinsky EP, Shigenaga M, Ames B, Kuypers FA, Klings ES. Erythrocyte glutamine depletion, altered redox environment, and pulmonary hypertension in sickle cell disease. Blood. 2008 Jan 1;111(1):402-10. Epub 2007 Sep 11. — View Citation

Morris CR, Vichinsky EP. Pulmonary hypertension in thalassemia. Ann N Y Acad Sci. 2010 Aug;1202:205-13. doi: 10.1111/j.1749-6632.2010.05580.x. — View Citation

Morris CR. Mechanisms of vasculopathy in sickle cell disease and thalassemia. Hematology Am Soc Hematol Educ Program. 2008:177-85. doi: 10.1182/asheducation-2008.1.177. Review. — View Citation

Morris CR. Vascular risk assessment in patients with sickle cell disease. Haematologica. 2011 Jan;96(1):1-5. doi: 10.3324/haematol.2010.035097. — View Citation

Niihara Y, Matsui NM, Shen YM, Akiyama DA, Johnson CS, Sunga MA, Magpayo J, Embury SH, Kalra VK, Cho SH, Tanaka KR. L-glutamine therapy reduces endothelial adhesion of sickle red blood cells to human umbilical vein endothelial cells. BMC Blood Disord. 2005 Jul 25;5:4. — View Citation

Walter PB, Fung EB, Killilea DW, Jiang Q, Hudes M, Madden J, Porter J, Evans P, Vichinsky E, Harmatz P. Oxidative stress and inflammation in iron-overloaded patients with beta-thalassaemia or sickle cell disease. Br J Haematol. 2006 Oct;135(2):254-63. — View Citation

Xu H, Pearl RG. Effect of l-glutamine on pulmonary hypertension in the perfused rabbit lung. Pharmacology. 1994 Apr;48(4):260-4. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Erythrocyte glutamine level	marker for oxidative stress	2 months
Primary	Tricuspid regurge velocity	Measures the risk of pulmonary hypertension	2 months
Secondary	Plasma glutamine level	Assess the glutamine level at each visit	2 months
Secondary	Liver function tests	Evaluates the state of liver	2 months
Secondary	Renal function tests	Evaluates the state of kidney	2 months
Secondary	Ferritin level	measuring the iron overload	2 months