Clinical trial NCT00305175: Long Term Effects of Hydroxyurea Therapy in Children With Sickle Cell Disease
Official title: Long Term Effects of Hydroxyurea Therapy in Children With Sickle Cell Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sickle Cell Disease
Keywords: Hydroxyurea
Sickle Cell Anemia
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: Children's Hospital Medical Center, Cincinnati
First posted: 2006-03-21
Enrollment: 260
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study participants will be patients with sickle cell disease who receive medical care from the Department of Hematology staff of St. Jude Children's Research Hospital. All patients on hydroxyurea therapy or patients who are initiating hydroxyurea therapy will be invited to participate.

Brief summary: The primary objectives of this prospective, observational study are (1) to describe the long-term cellular, molecular, and clinical effects of hydroxyurea therapy in sickle cell disease, and (2) to perform hydroxyurea pharmacokinetics studies.

This study will follow sickle cell patients being treated with hydroxyurea for a long period of time to evaluate the long-term cellular and molecular effects of the drug on the patients' body. This study will consist of two patient groups. One group will be made up of patients who have received hydroxyurea therapy before entering the study. The second group will be made up of patients who have not received hydroxyurea before study entry.

Detailed description: Many years of study have documented the severe effects of sickle cell disease. Some of these effects include hemolysis (the break down of red blood cells), blockages in the blood vessels, and damage to the organs systems of the body. Hydroxyurea, which is given by mouth, is used to effectively prevent blockages in the blood vessels of patients with sickle cell disease. The hydroxyurea dosage varies and the responses of the body to this drug are not well understood.

This study will follow sickle cell patients being treated with hydroxyurea for a long period of time to evaluate the long-term cellular and molecular effects of the drug on the patients' body. This study will consist of two patient groups. One group will be made up of patients who have received hydroxyurea therapy before entering the study (Old Cohort). The second group will be made up of patients who have not received hydroxyurea before study entry (New Cohort).

This is not a therapeutic drug trial. Subjects for this study will receive hydroxyurea therapy for accepted clinical indications, and will be treated per best clinical management using treatment algorithms established at St. Jude Children's Research Hospital and other pediatric sickle cell programs across the United States. Hydroxyurea therapy data (such as dosing and duration of therapy) will not be dictated by this study, but will be collected to correlate with long-term outcomes. Hydroxyurea dose escalation to a stable MTD will occur according to published guidelines.

Eligibility criteria: Inclusion Criteria:

* Patients from birth up to age 30 years
* Diagnosis of sickle cell disease
* Patients who are receiving hydroxyurea therapy or plan to begin hydroxyurea therapy

Primary outcomes:
measure: DNA damage from hydroxyurea therapy-variable-diversity-joining (VDJ) recombination events defined as the number of events per microgram of genomic DNA;
timeFrame: Every 3 years
measure: DNA damage from hydroxyurea therapy-percentage of HJB in immature (CD71+) erythrocytes
timeFrame: Every 3 years
Secondary outcomes:
measure: Brain function as measured by MRI/MRA and TCD
timeFrame: Every 3 years
measure: Splenic function as measured by Spleen Scan
timeFrame: Every 3 years
measure: Kidney function as measured by BUN/creatinine and Urinalysis, glomerular filtration rate (GFR)
timeFrame: Every 3 years
measure: Lung function as measured by forced vital capacity (FVC) (%), forced vital volume in 1 second (FVC1) (%), and tricuspid regurgitation (TR) jet on Echocardiogram (ECHO)
timeFrame: Every 3 years
measure: Growth as measured by height and weight
timeFrame: Every visit
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Jeremie Estepp, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aygun B, Mortier NA, Smeltzer MP, Shulkin BL, Hankins JS, Ware RE. Hydroxyurea treatment decreases glomerular hyperfiltration in children with sickle cell anemia. Am J Hematol. 2013 Feb;88(2):116-9. doi: 10.1002/ajh.23365. Epub 2012 Dec 17.
citation: Flanagan JM, Steward S, Howard TA, Mortier NA, Kimble AC, Aygun B, Hankins JS, Neale GA, Ware RE. Hydroxycarbamide alters erythroid gene expression in children with sickle cell anaemia. Br J Haematol. 2012 Apr;157(2):240-8. doi: 10.1111/j.1365-2141.2012.09061.x. Epub 2012 Feb 24.
citation: Walker AL, Steward S, Howard TA, Mortier N, Smeltzer M, Wang YD, Ware RE. Epigenetic and molecular profiles of erythroid cells after hydroxyurea treatment in sickle cell anemia. Blood. 2011 Nov 17;118(20):5664-70. doi: 10.1182/blood-2011-07-368746. Epub 2011 Sep 14.
citation: Flanagan JM, Howard TA, Mortier N, Avlasevich SL, Smeltzer MP, Wu S, Dertinger SD, Ware RE. Assessment of genotoxicity associated with hydroxyurea therapy in children with sickle cell anemia. Mutat Res. 2010 Apr 30;698(1-2):38-42. doi: 10.1016/j.mrgentox.2010.03.001. Epub 2010 Mar 15.