Long Term Effects of Erythrocyte Lysis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00842621
First received: February 11, 2009
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

In this prospective observational trial, participants with chronic hemolysis will be assessed with echocardiogram for elevated tricuspid jet velocity and other evidence of pulmonary hypertension. Participants will have laboratory studies evaluating: severity of hemolysis, splenic function, inflammation, endothelial dysfunction, and hypercoagulability. There will be 3 main categories of participants enrolled in this study: (1) pediatric participants with severe sickle cell disease (SCD) (HbSS, HbS/β° thalassemia ) who are not receiving treatment (e.g., hydroxyurea or chronic transfusions); (2) pediatric participants with other forms of SCD or severe SCD (HbSS, HbS/β° thalassemia) patients being treated with hydroxyurea or chronic transfusions; and (3) pediatric and adult participants with other non-sickling hematological disorders.


Condition Intervention
Sickle Cell Disease
Hemolytic Anemia
Procedure: Clinical Evaluations
Other: Laboratory Studies

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Long Term Effects of Erythrocyte Lysis

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • 1.To investigate the relationship between tricuspid regurgitation jet velocity (TRV) and intravascular hemolysis, as measured by serum lactate dehydrogenase (LDH), in untreated children with severe sickle cell disease(HbSS or Hb S/β°-thalassemia. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Blood Serum Plasma Urine


Enrollment: 390
Study Start Date: March 2009
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
Pediatric participants with severe sickle cell disease (HbSS or Hb S/β°-thalassemia) who are not receiving treatment, e.g., hydroxyurea or chronic transfusions
Procedure: Clinical Evaluations
All clinical evaluations should be performed greater than 30 days from illness or hospitalization. Participants will have weight, height, body mass index (BMI), heart rate, respiratory rate, blood pressure (systolic and diastolic) and pulse oximetry recorded while at rest on room air by clinical staff. Cardiac examination will be performed by echocardiogram.
Other: Laboratory Studies

Blood for:

Complete Blood Count with Differential, Reticulocyte Count, Micronuclei enumeration, α-globin genotype, G6PD activity, genotype, SNP array,

Serum for:

Soluble VCAM-1, ICAM-1, Soluble CD40L, Arginase, Endothelin-1, Prothrombin Fragment 1+2, IL-6, -8, -10, Soluble E-selectin, NOx, Haptoglobin, Tumor necrosis factor alpha

Plasma for:

Chemistry 18, Cystatin-C, Ferritin, Lactate Dehydrogenase, C-reactive protein, Erythropoietin, NT-proBNP, Haptoglobin, Von Willibrand Factor Antigen, D-dimer, Factor VIII Assay, Quantitative amino acids, Free hemoglobin, Tumor necrosis factor- α, Thrombin-Antithrombin complex, endothelin-1

Urine for:

Urinalysis, Urine spot protein, creatinine, Microalbumin, Urine hemosiderin, Urine hepcidin

2
Pediatric participants with other forms of SCD or severe sickle cell disease patients (HbSS or Hb S/β°-thalassemia) being treated with hydroxyurea or chronic transfusions
Procedure: Clinical Evaluations
All clinical evaluations should be performed greater than 30 days from illness or hospitalization. Participants will have weight, height, body mass index (BMI), heart rate, respiratory rate, blood pressure (systolic and diastolic) and pulse oximetry recorded while at rest on room air by clinical staff. Cardiac examination will be performed by echocardiogram.
Other: Laboratory Studies

Blood for:

Complete Blood Count with Differential, Reticulocyte Count, Micronuclei enumeration, α-globin genotype, G6PD activity, genotype, SNP array,

Serum for:

Soluble VCAM-1, ICAM-1, Soluble CD40L, Arginase, Endothelin-1, Prothrombin Fragment 1+2, IL-6, -8, -10, Soluble E-selectin, NOx, Haptoglobin, Tumor necrosis factor alpha

Plasma for:

Chemistry 18, Cystatin-C, Ferritin, Lactate Dehydrogenase, C-reactive protein, Erythropoietin, NT-proBNP, Haptoglobin, Von Willibrand Factor Antigen, D-dimer, Factor VIII Assay, Quantitative amino acids, Free hemoglobin, Tumor necrosis factor- α, Thrombin-Antithrombin complex, endothelin-1

Urine for:

Urinalysis, Urine spot protein, creatinine, Microalbumin, Urine hemosiderin, Urine hepcidin

3
Pediatric and adult participants with other non-sickling hematological disorders
Procedure: Clinical Evaluations
All clinical evaluations should be performed greater than 30 days from illness or hospitalization. Participants will have weight, height, body mass index (BMI), heart rate, respiratory rate, blood pressure (systolic and diastolic) and pulse oximetry recorded while at rest on room air by clinical staff. Cardiac examination will be performed by echocardiogram.
Other: Laboratory Studies

Blood for:

Complete Blood Count with Differential, Reticulocyte Count, Micronuclei enumeration, α-globin genotype, G6PD activity, genotype, SNP array,

Serum for:

Soluble VCAM-1, ICAM-1, Soluble CD40L, Arginase, Endothelin-1, Prothrombin Fragment 1+2, IL-6, -8, -10, Soluble E-selectin, NOx, Haptoglobin, Tumor necrosis factor alpha

Plasma for:

Chemistry 18, Cystatin-C, Ferritin, Lactate Dehydrogenase, C-reactive protein, Erythropoietin, NT-proBNP, Haptoglobin, Von Willibrand Factor Antigen, D-dimer, Factor VIII Assay, Quantitative amino acids, Free hemoglobin, Tumor necrosis factor- α, Thrombin-Antithrombin complex, endothelin-1

Urine for:

Urinalysis, Urine spot protein, creatinine, Microalbumin, Urine hemosiderin, Urine hepcidin


Detailed Description:
  1. The study will investigate the relationship between tricuspid regurgitation jet velocity (TRV) and intravascular hemolysis, as measured by serum lactate dehydrogenase (LDH), in untreated children with severe sickle cell disease (HbSS or Hb S/β°-thalassemia)
  2. The Study will estimate the prevalence of elevated TRV (≥ 2.5 m/s) in untreated children with severe sickle cell disease (HbSS or Hb S/β°-thalassemia), as measured by echocardiography.

Secondary objectives for this study include the following:

  1. To estimate the prevalence of elevated TRV in children with severe sickle cell disease (HbSS or Hb S/β°-thalassemia) receiving hydroxyurea or chronic transfusion therapy.
  2. To estimate the prevalence of elevated TRV in children with other forms of hemolytic anemia, including other sickling disorders (such as HbSC or HbS/β+-thalassemia) and non-sickling hemolytic anemia (such as hereditary spherocytosis).
  3. To estimate the prevalence of elevated TRV in adults with non-sickling hemolytic anemia, with or without splenic function.
  4. To investigate the association between TRV and splenic function
  5. To investigate the associations between TRV and laboratory parameters of inflammation and hypercoagulability, such as white blood cell count, platelet count, serum N-terminal pro-brain natriuretic peptide (NT-proBNP),endothelial dysfunction, and other markers of hemolysis (bilirubin, plasma free hemoglobin, haptoglobin, etc.)
  6. To evaluate genetic determinants of elevated TRV in children and adults with hemolytic anemia.
  7. To investigate changes in TRV and hemolysis over time using serial measurements 2 ± 0.5 years after initial enrollment testing.
  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Children aged 5 years of age up to 19th birthday with sickle cell disease or other forms of hemolytic anemia; Adults over the age of 18 with non-sickling hemolytic anemia.

Criteria

Inclusion Criteria:

  1. Established Diagnosis of Hemolysis

    • Sickle Cell Disease (e.g., HbSS, HbS/β-thalassemia, HbSC)
    • Other conditions with hemolysis (e.g., RBC membranopathies, enzymopathies, unstable hemoglobinopathies, PNH)
  2. Age

    • SCD participants: 5 years of age up to 19th birthday
    • All other participants: 5 years of age and up (no age limit)

Exclusion Criteria:

  1. Previous cardiac surgery
  2. Known left ventricle dysfunction (i.e. shortening fraction < 28%)
  3. Known right sided congenital heart defect such as atrial septal defect or pulmonary valve stenosis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00842621

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38115
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Jane Hankins, MD, MS St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00842621     History of Changes
Other Study ID Numbers: ELYSIS
Study First Received: February 11, 2009
Last Updated: July 22, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Sickle Cell Disease, Hemolytic Anemia
Hemolysis

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic
Anemia, Hemolytic, Congenital
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on September 16, 2014