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

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

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

Study Overview

• Status: Completed
• Conditions: Hemolysis; Pulmonary Hypertension; Thalassemia in Children
• Intervention / Treatment: Diagnostic test: blood sample; Diagnostic test: Tricuspid regurge velocity

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt
    • Assiut University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Upper Egypt thalassemic children aged 10-18 years old attending Assiut University Children Hospital.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
on chelation; patients with B-thalassemia major samples of which will be examined for renal and liver function, Erythrocyte Glutamine level, ferritin level and complete blood picture. Also Echo will be done for measuring the Tricuspid regurge velocity. group 1: cases on chelation: deferasirox 500mg oral tablet with initial dose 20 mg/kg guided by ferritin level Diagnostic Test: blood sample Diagnostic Test: Tricuspid regurge velocity	Diagnostic test: blood sample; blood sample for measuring liver and kidney function, CBC, ferritin level and erythrocyte glutamine level; Diagnostic test: Tricuspid regurge velocity; Tricuspid regurge velocity will be measured by doppler echocardiography denoting the pulmonary hypertension risk in children
No chelation; group 2: cases without chelation Diagnostic Test: blood sample Diagnostic Test: Tricuspid regurge velocity	Diagnostic test: blood sample; blood sample for measuring liver and kidney function, CBC, ferritin level and erythrocyte glutamine level; Diagnostic test: Tricuspid regurge velocity; Tricuspid regurge velocity will be measured by doppler echocardiography denoting the pulmonary hypertension risk in children
splenectomy; group 3: cases with splenectomy Diagnostic Test: blood sample Diagnostic Test: Tricuspid regurge velocity	Diagnostic test: blood sample; blood sample for measuring liver and kidney function, CBC, ferritin level and erythrocyte glutamine level; Diagnostic test: Tricuspid regurge velocity; Tricuspid regurge velocity will be measured by doppler echocardiography denoting the pulmonary hypertension risk in children
no splenectomy; group 4: cases without splenectomy Diagnostic Test: blood sample Diagnostic Test: Tricuspid regurge velocity	Diagnostic test: blood sample; blood sample for measuring liver and kidney function, CBC, ferritin level and erythrocyte glutamine level; Diagnostic test: Tricuspid regurge velocity; Tricuspid regurge velocity will be measured by doppler echocardiography denoting the pulmonary hypertension risk in children

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Erythrocyte glutamine level	marker for oxidative stress	2 months
Tricuspid regurge velocity	Measures the risk of pulmonary hypertension	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma glutamine level	Assess the glutamine level at each visit	2 months
Liver function tests	Evaluates the state of liver	2 months
Renal function tests	Evaluates the state of kidney	2 months
Ferritin level	measuring the iron overload	2 months

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Fahim M Fahim, PhD, Children Hospital, Assiut University; Principal Investigator: Fatma S AbdElshafi, bachelor's, Children Hospital, Assiut University; Principal Investigator: Eman F. Mohamed, PhD, Children Hospital, Assiut University

Publications and helpful links

General Publications

• 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. doi: 10.1056/NEJMoa035477.
• 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. doi: 10.1002/ajh.21058.
• 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.
• 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. doi: 10.1111/j.1365-2141.2006.06277.x.
• 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. doi: 10.1182/blood-2007-04-081703. Epub 2007 Sep 11.
• 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. doi: 10.1196/annals.1345.058.
• 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.
• 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.
• Kuypers FA. Membrane lipid alterations in hemoglobinopathies. Hematology Am Soc Hematol Educ Program. 2007:68-73. doi: 10.1182/asheducation-2007.1.68.
• 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. doi: 10.1002/ajh.20809.
• 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.
• 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. Erratum In: Heart. 2011 Jul;97(13):1112.
• 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. doi: 10.1164/rccm.200610-1498OC. Epub 2007 Mar 22.
• Morris CR. Vascular risk assessment in patients with sickle cell disease. Haematologica. 2011 Jan;96(1):1-5. doi: 10.3324/haematol.2010.035097. No abstract available.
• 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.
• Xu H, Pearl RG. Effect of l-glutamine on pulmonary hypertension in the perfused rabbit lung. Pharmacology. 1994 Apr;48(4):260-4. doi: 10.1159/000139188.
• 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. doi: 10.1186/1471-2326-5-4.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): August 25, 2019
• Study Completion (Actual): August 26, 2019

Study Registration Dates

• First Submitted: April 15, 2017
• First Submitted That Met QC Criteria: April 25, 2017
• First Posted (Actual): April 28, 2017

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 26, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Pulmonary hypertension; Thalassemia; Glutamine/glutamate ratio
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Hypertension; Hypertension, Pulmonary; Thalassemia; beta-Thalassemia; Hemolysis
• Other Study ID Numbers: GlnThalassemia

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No