Long Term Effects of Hydroxyurea Therapy in Children With Sickle Cell Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by St. Jude Children's Research Hospital
Sponsor:
Collaborator:
Children's Hospital Medical Center, Cincinnati
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00305175
First received: March 17, 2006
Last updated: April 15, 2014
Last verified: April 2014
  Purpose

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.


Condition
Sickle Cell Disease

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Long Term Effects of Hydroxyurea Therapy in Children With Sickle Cell Disease

Resource links provided by NLM:


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

Primary Outcome Measures:
  • DNA damage from hydroxyurea therapy-variable-diversity-joining (VDJ) recombination events defined as the number of events per microgram of genomic DNA; [ Time Frame: Every 3 years ] [ Designated as safety issue: Yes ]
  • DNA damage from hydroxyurea therapy-percentage of HJB in immature (CD71+) erythrocytes [ Time Frame: Every 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Brain function as measured by MRI/MRA and TCD [ Time Frame: Every 3 years ] [ Designated as safety issue: No ]
    optional test

  • Splenic function as measured by Spleen Scan [ Time Frame: Every 3 years ] [ Designated as safety issue: No ]
    optional test

  • Kidney function as measured by BUN/creatinine and Urinalysis, glomerular filtration rate (GFR) [ Time Frame: Every 3 years ] [ Designated as safety issue: No ]
    optional test

  • Lung function as measured by forced vital capacity (FVC) (%), forced vital volume in 1 second (FVC1) (%), and tricuspid regurgitation (TR) jet on Echocardiogram (ECHO) [ Time Frame: Every 3 years ] [ Designated as safety issue: No ]
    collected if performed for clinical purposes

  • Growth as measured by height and weight [ Time Frame: Every visit ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Whole Blood


Estimated Enrollment: 300
Study Start Date: March 2006
Estimated Study Completion Date: January 2026
Estimated Primary Completion Date: January 2026 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
Patients who have received hydroxyurea therapy before entering the study.
2
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

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  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: NCT00305175

Contacts
Contact: Kerri Nottage, MD 1-866-278-5833 info@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Kerri Nottage, MD    866-278-5833    info@stjude.org   
Sponsors and Collaborators
St. Jude Children's Research Hospital
Children's Hospital Medical Center, Cincinnati
Investigators
Principal Investigator: Kerri Nottage, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided by St. Jude Children's Research Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00305175     History of Changes
Other Study ID Numbers: HUSTLE
Study First Received: March 17, 2006
Last Updated: April 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Hydroxyurea
Sickle Cell Anemia

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Hydroxyurea
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antisickling Agents
Hematologic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014