Sickle Cell DiseaseNCT00305175
Long Term Effects of Hydroxyurea Therapy in Children With Sickle Cell Disease
An observational study of Sickle Cell Disease, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 30 years
- Conditions the study is for
- Sickle Cell Disease
- How many people
- 260 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Mar 2006to 23 Apr 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
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.
Who may be able to join
- 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
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
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.
Read the 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.
- Conditions
- Sickle Cell Disease
- Keywords
- Hydroxyurea, Sickle Cell Anemia
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
DNA damage from hydroxyurea therapy-variable-diversity-joining (VDJ) recombination events defined as the number of events per microgram of genomic DNA;
Measured: Every 3 years
DNA damage from hydroxyurea therapy-percentage of HJB in immature (CD71+) erythrocytes
Measured: Every 3 years
Secondary outcomes (5)
Brain function as measured by MRI/MRA and TCD
optional test
Measured: Every 3 years
Splenic function as measured by Spleen Scan
optional test
Measured: Every 3 years
Kidney function as measured by BUN/creatinine and Urinalysis, glomerular filtration rate (GFR)
optional test
Measured: 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)
collected if performed for clinical purposes
Measured: Every 3 years
Growth as measured by height and weight
Measured: Every visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2006 (estimated)
- Study start3 Mar 2006
- Primary completion23 Apr 2015
- Study completion23 Apr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 260 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital Medical Center, Cincinnati
- Responsible party
- Sponsor
- Investigators
- Jeremie Estepp, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00305175
- Sponsor's protocol ID
- HUSTLE
- Status last verified
- Jul 2020
- First submitted
- 17 Mar 2006
- Last updated
- 28 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Power-Hays A, McElhinney KE, Williams TN, Mochamah G, Olupot-Olupot P, Paasi G, Reid ME, Rankine-Mullings AE, Opoka RO, John CC, McGann PT, Quinn CT, Punt NC, Smart LR, Stuber SE, Latham TS, Vinks AA, Ware RE. Hydroxyurea pharmacokinetics in children with sickle cell anemia across different global populations. Blood Adv. 2026 Jan 27;10(2):418-427. doi: 10.1182/bloodadvances.2025017254.
PubMed 41026975Aygun 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.
PubMed 23255310Flanagan 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.
PubMed 22360576Walker 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.
PubMed 21921042Flanagan 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.
PubMed 20230905
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long Term Effects of Hydroxyurea Therapy in Children With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT00305175
- Acronym / sponsor ID
- HUSTLE
- Conditions
- Sickle Cell Disease
- Keywords
- Hydroxyurea, Sickle Cell Anemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 260 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Collaborators
- Children's Hospital Medical Center, Cincinnati
- Study start
- 3 Mar 2006 (actual)
- Primary completion
- 23 Apr 2015 (actual)
- Study completion
- 23 Apr 2015 (actual)
- First posted
- 21 Mar 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- Up to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
DNA damage from hydroxyurea therapy-percentage of HJB in immature (CD71+) erythrocytes
Time frame: Every 3 years
5 secondary outcomes
Brain function as measured by MRI/MRA and TCD
Time frame: Every 3 years
Splenic function as measured by Spleen Scan
Time frame: Every 3 years
Kidney function as measured by BUN/creatinine and Urinalysis, glomerular filtration rate (GFR)
Time frame: 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)
Time frame: Every 3 years
Growth as measured by height and weight
Time frame: Every visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2020.
- Derived from this study: PubMed 41026975Power-Hays A, McElhinney KE, Williams TN, Mochamah G, Olupot-Olupot P, Paasi G, Reid ME, Rankine-Mullings AE, Opoka RO, John CC, McGann PT, Quinn CT, Punt NC, Smart LR, Stuber SE, Latham TS, Vinks AA, Ware RE. Hydroxyurea pharmacokinetics in children with sickle cell anemia across different global populations. Blood Adv. 2026 Jan 27;10(2):418-427. doi: 10.1182/bloodadvances.2025017254.
- Derived from this study: PubMed 23255310Aygun 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.
- Derived from this study: PubMed 22360576Flanagan 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.
- Derived from this study: PubMed 21921042Walker 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.
- Derived from this study: PubMed 20230905Flanagan 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.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeremie Estepp, MD principal investigator
St. Jude Children's Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cell Disease, run by St. Jude Children's Research Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00305175, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2020.