Long Term Effects of Hydroxyurea Therapy in Children With Sickle Cell Disease
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.
Studieoversikt
Status
Forhold
Detaljert beskrivelse
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.
Studietype
Registrering (Faktiske)
Kontakter og plasseringer
Studiesteder
-
-
Tennessee
-
Memphis, Tennessee, Forente stater, 38105
- St. Jude Children's Research Hospital
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Prøvetakingsmetode
Studiepopulasjon
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
Kohorter og intervensjoner
Gruppe / Kohort |
|---|
|
Patients With Prior Hydroxyurea
Patients who have received hydroxyurea therapy before entering the study.
|
|
Patients Without Prior Hydroxyurea
Patients who have not received hydroxyurea before study entry.
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
DNA damage from hydroxyurea therapy-variable-diversity-joining (VDJ) recombination events defined as the number of events per microgram of genomic DNA;
Tidsramme: Every 3 years
|
Every 3 years
|
|
DNA damage from hydroxyurea therapy-percentage of HJB in immature (CD71+) erythrocytes
Tidsramme: Every 3 years
|
Every 3 years
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Brain function as measured by MRI/MRA and TCD
Tidsramme: Every 3 years
|
optional test
|
Every 3 years
|
|
Splenic function as measured by Spleen Scan
Tidsramme: Every 3 years
|
optional test
|
Every 3 years
|
|
Kidney function as measured by BUN/creatinine and Urinalysis, glomerular filtration rate (GFR)
Tidsramme: Every 3 years
|
optional test
|
Every 3 years
|
|
Lung function as measured by forced vital capacity (FVC) (%), forced vital volume in 1 second (FVC1) (%), and tricuspid regurgitation (TR) jet on Echocardiogram (ECHO)
Tidsramme: Every 3 years
|
collected if performed for clinical purposes
|
Every 3 years
|
|
Growth as measured by height and weight
Tidsramme: Every visit
|
Every visit
|
Samarbeidspartnere og etterforskere
Samarbeidspartnere
Publikasjoner og nyttige lenker
Generelle publikasjoner
- 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.
- 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.
- 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.
- 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.
Hjelpsomme linker
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- HUSTLE
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
Kliniske studier på Sigdcellesykdom
-
Second Affiliated Hospital of Guangzhou Medical...Hunan Zhaotai Yongren Medical Innovation Co. Ltd.RekrutteringAnti-kreft celle immunterapi | T Cell og NK CellKina
-
Peking University People's HospitalUkjentNatural Killer Cell Medited ImmunitetKina
-
Center for International Blood and Marrow Transplant...Cellular Dynamics International, Inc. - A FUJIFILM CompanyAvsluttetiPS Cell Manufacturing and Banking
-
Medtronic - MITGAvsluttetEsophageal squamous cell neoplasia (ESCN)Kina
-
Assistance Publique - Hôpitaux de ParisHar ikke rekruttert ennå
-
Bing HanFullførtPure Red Cell Aplasia, ervervetKina
-
Debiopharm International SARekrutteringPankreas duktal adenokarsinom (PDAC) | Kolorektal kreft (CRC) | Clear Cell Renal Cell Cancer (ccRCC)Frankrike, Australia
-
Calla IVF CenterFullførtImmunmodulerende legemidler | Killer-cell immunoglobulin-lignende reseptorer (KIR) | KIR Alleles (KIR AA)Romania
-
Institute of Hematology & Blood Diseases Hospital...AvsluttetErvervet Pure Red Cell AplasiaKina
-
Peking Union Medical College HospitalUkjent