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

NCT03133169 | Completed

• 1 other identifier: GlnThalassemia
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Thalassemia in Children; Pulmonary Hypertension; Hemolysis

Keywords

Thalassemia; Glutamine/glutamate ratio; Pulmonary hypertension

Outcome Measures

Primary Outcomes (2)

• Erythrocyte glutamine level

  marker for oxidative stress

  2 months

• Tricuspid regurge velocity

  Measures the risk of pulmonary hypertension

  2 months

Secondary Outcomes (4)

• Plasma glutamine level

  2 months

• Liver function tests

  2 months

• Renal function tests

  2 months

• Ferritin level

  2 months

Study Arms (4)

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; Diagnostic Test: Tricuspid regurge velocity

No chelation

group 2: cases without chelation Diagnostic Test: blood sample Diagnostic Test: Tricuspid regurge velocity

Diagnostic Test: blood sample; Diagnostic Test: Tricuspid regurge velocity

splenectomy

group 3: cases with splenectomy Diagnostic Test: blood sample Diagnostic Test: Tricuspid regurge velocity

Diagnostic Test: blood sample; Diagnostic Test: Tricuspid regurge velocity

no splenectomy

group 4: cases without splenectomy Diagnostic Test: blood sample Diagnostic Test: Tricuspid regurge velocity

Diagnostic Test: blood sample; Diagnostic Test: Tricuspid regurge velocity

Interventions

blood sample DIAGNOSTIC_TEST

blood sample for measuring liver and kidney function, CBC, ferritin level and erythrocyte glutamine level

No chelation; no splenectomy; on chelation; splenectomy

Tricuspid regurge velocity DIAGNOSTIC_TEST

Tricuspid regurge velocity will be measured by doppler echocardiography denoting the pulmonary hypertension risk in children

No chelation; no splenectomy; on chelation; splenectomy

Eligibility Criteria

• Age: 10 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Assiut University

Asyut, Egypt

Location

Related Publications (18)

• 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.

  PMID: 14985486 BACKGROUND

• 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.

  PMID: 16339702 BACKGROUND

• 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.

  PMID: 20712794 BACKGROUND

• 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.

  PMID: 17010049 BACKGROUND

• 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.

  PMID: 19074078 BACKGROUND

• Kuypers FA. Membrane lipid alterations in hemoglobinopathies. Hematology Am Soc Hematol Educ Program. 2007:68-73. doi: 10.1182/asheducation-2007.1.68.

  PMID: 18024611 BACKGROUND

• 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.

  PMID: 17094096 BACKGROUND

• 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.

  PMID: 20522578 BACKGROUND

• 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.

  PMID: 21357375 BACKGROUND

• 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.

  PMID: 17724699 BACKGROUND

• 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.

  PMID: 17379852 BACKGROUND

• 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.

  PMID: 21264896 BACKGROUND

• 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.

  PMID: 21193426 BACKGROUND

• 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.

  PMID: 22175008 BACKGROUND

• 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.

  PMID: 8177911 BACKGROUND

• 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.

  PMID: 17848621 BACKGROUND

• 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.

  PMID: 16042803 BACKGROUND

• 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.

  PMID: 24267302 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma sample

MeSH Terms

Conditions

Hypertension, Pulmonary; Hemolysis; Thalassemia

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Resident

Study Record Dates

• First Submitted: April 15, 2017
• First Posted: April 28, 2017
• Study Start: June 1, 2017
• Primary Completion: August 25, 2019
• Study Completion: August 26, 2019
• Last Updated: August 28, 2019

Record last verified: 2019-08

Locations

EG (1)