Sickle Cell DiseasePhase 1/2NOHARM MTDNCT07708714
Optimizing Hydroxyurea Therapy in Children With Sickle Cell Anemia In Malaria Endemic Areas: The NOHARM Maximum Tolerated Dose (MTD) Study
A Phase 1/2 study testing hydroxycarbamide in people with Sickle Cell Disease and Sickle Cell Anemia in Children, run by Children's Hospital Medical Center, Cincinnati at 1 site in Uganda.
Trial summary
NOHARM MTD is an extension of a previous study for children with Sickle Cell Anemia (SCA) who were enrolled in the NOHARM study. All children enrolled in NOHARM received hydroxyurea treatment at a fixed daily dose of 20 mg/kg/day. Read more about this study
- Who is it for?
- Ages 11 to 18 years
- Conditions the study is for
- Sickle Cell Disease, Sickle Cell Anemia in Children
- What is being tested?
- hydroxycarbamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 1 siteUganda
- Study dates
- 13 May 2026to 30 Nov 2032
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 11 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Adolescents with confirmed SCA who are currently enrolled in the NOHARM MTD Study of hydroxyurea at the Mulago Hospital Sickle Cell Clinic (MHSCC), will be eligible for the NOHARM MTD LT version 2.0 extension study after completing re-consent. An age-matched untreated (hydroxyurea-naïve) group of adolescents will also be enrolled as a Comparator Cohort. This will comprise 75 children from Kampala and surrounding districts, ages 11 - 18 years of age, with confirmed SCA.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Uganda1 site, 1 recruiting
- Recruiting
Mulago Hospital Sickle Cell Clinic
Kampala
Grace Ndeezi, MD, MMED PhD
About this study
NOHARM MTD is an extension of a previous study for children with Sickle Cell Anemia (SCA) who were enrolled in the NOHARM study. All children enrolled in NOHARM received hydroxyurea treatment at a fixed daily dose of 20 mg/kg/day. This dose was selected as a likely safe dose, but does not escalate hydroxyurea to maximum tolerated dose "MTD" as is commonly done in the US. Without this information, we cannot know whether hydroxyurea treatment at the MTD would be feasible (since it requires closer monitoring to avoid hematological toxicities), safe (since adverse events may be greater with MTD, risk of malaria may be altered by MTD, and risk of infections as a result of neutropenia could also be greater with MTD) or beneficial (MTD is associated with higher hemoglobin and fetal hemoglobin concentration).
Read the detailed description
The purpose of this study is to determine the long-term effects of hydroxyurea treatment on internal organs, the best dosing strategies for children with SCA in Africa, and to identify any genetic factors that affect how a child responds to the study medication. All children in this study will receive the research treatment, hydroxyurea. Hydroxyurea is used to prevent SCA pain episodes and is approved by the European Medicines Agency for adults, adolescents, and children over two-years-old with SCA. During quarterly visits, we will collect information about your child with the study medication, hydroxyurea. This study is being conducted by Dr. Russell Ware at Cincinnati Children's Hospital Medical Center (CCHMC) and his Co-Investigators including Professor Grace Ndeezi and Dr. Phillip Kasirye at the Mulago Hospital Sickle Cell Clinic, and the hydroxyurea medicine is supplied by the manufacturer.
The goal of this clinical trial is to assess the long-term risks and benefits of open-label dose-escalated oral hydroxyurea in a large cohort of Ugandan adolescents with sickle cell anemia (SCA). Additional objectives include investigation of hydroxyurea pharmacokinetics (PK) and pharmacodynamics (PD) in this population, and investigation of the drug's mechanisms of action through advanced genomics and multiomics analysis.
The main questions it aims to answer are:
Aim 1. To determine the safety and efficacy of maximum tolerated dose (MTD) vs. fixed dose (20 mg/kg/day) hydroxyurea treatment in children with SCA in a low-resource, malaria endemic setting. For safety, we will compare adverse events and severe adverse events, including hematologic toxicities. For efficacy, we will assess hemoglobin level, fetal hemoglobin percentage (% HbF), and incidence of vaso-occlusive events such as pain crisis and acute chest syndrome.
Aim 2. To compare the clinical outcomes of MTD vs. fixed dose hydroxyurea treatment in children with SCA in a low-resource, malaria endemic setting. Clinical outcomes assessed will include growth and malaria incidence over a 24-month follow-up period, and differences in renal, splenic, and cerebrovascular function between study entry and 24-month follow-up.
Aim 3. To obtain long-term follow up data to assess laboratory and clinical effects as well as annual visits for organ function (liver, kidneys, spleen, brain) and growth/development.
Aim 4. Quantify the long-term benefits and risks of extended hydroxyurea treatment at MTD. We hypothesize that early and sustained hydroxyurea at MTD can (1) decrease the prevalence of organ damage; (2) improve growth and development; (3) preserve fertility; and (4) maintain a low risk for mutagenic genotoxicity. Protection against organ injury will be assessed in brain (Transcranial Doppler, MRI/MRA, and cerebral oxygenation); heart (echocardiogram); lungs (pulse oximetry, spirometry); kidney (length, glomerular filtration rate, albuminuria, and urine biomarkers); spleen (volume, erythrocyte micronuclei for filtrative function); bones (MRI for avascular necrosis, dual-energy X-ray absorptiometry for bone density); immunological competency (antibody titers to vaccines and malaria exposures); growth and development (standard auxologic measures, Tanner staging, growth hormones); fertility (sex hormones AMH/FSH/LH); and genotoxicity (clonal hematopoiesis, reticulocyte micronuclei).
Aim 5. Define and analyze hydroxyurea pharmacokinetics (PK) and pharmacodynamics (PD) profiles. We hypothesize that PK and PD hydroxyurea profiles will have substantial inter-patient variability. Both the Original Cohort and an untreated Comparator Cohort will undergo formal PK analysis using serial blood samples and a novel point-of-care assay to quantify hydroxyurea levels for calculating PK parameters and optimal dosing. With pharmacometrics analysis, these PK parameters will then be correlated with PD variables, including treatment responses (HbF) and hydroxyurea dose. These PK-PD associations will also be analyzed by age, hydroxyurea dose, and renal function.
Aim 6. Perform genomics analysis for genes influencing hydroxyurea treatment responses and modern multi-omics analysis with proteomics and metabolomics to help elucidate the drug's mechanism of action. We hypothesize that novel genetic variants affect key parameters such as optimal dose and HbF response. In addition to examining known or suspected target genes, we will use a univariate linear mixed model and genome-wide efficient mixed model association to analyze results of unbiased whole exome sequencing and genome-wide array data. We will also perform serial metabolomics and proteomics on samples collected before and during hydroxyurea treatment, to help identify useful biomarkers and signatures of treatment response, and elucidate pathways for hydroxyurea's mechanism of action.
Participants ages 11-16 years old will have information collected for up to 5 years which include:
- Physical Exam and Medical History
- Blood
- Urine Sample
- Near Infrared Spectroscopy
- Transcranial Doppler
- Pharmacokinetics Study
- Echocardiogram
- Spirometry
- Abdominal Ultrasound
- Brain MRI and MRA
- Hip and hand/wrist MRI
- Dual energy X-ray absorptiometry (DEXA)
- Quality of Life
- Physical Exam and Medical History
- Blood Sample
- Hydroxyurea medication
Children will take the maximum tolerated dose of hydroxyurea. A dose determined by pharmacokinetic-guided hydroxyurea initiation and subsequent optimization.
- Being tested
- hydroxycarbamide
- 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.
hydroxycarbamideDrug
Hydroxyurea at optimized dose
| Study group | Role | What they receive |
|---|---|---|
| Hydroxyurea: Original NOHARM Cohort | Experimental | Original Cohort, continue hydroxyurea at optimized dose Receives: Drug: hydroxycarbamide |
| Hydroxyurea: New Comparator Cohort | Experimental | New, untreated cohort, initiate and optimize hydroxyurea dose Receives: Drug: hydroxycarbamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite measure of organ damage
The primary study endpoint will be a composite measure of organ damage to the brain (defined as ≥2 silent cerebral infarcts on brain MRI or ≥170 cm/sec flow velocities by TCD) or the kidneys (confirmed micro- or macro-albuminuria), or bones (femoral head AVN, Mitchell Stage B or higher).
Measured: From enrollment, after 24 months and again after 48 months of study treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2026
- Study start13 May 2026
- Primary completion30 Nov 2030 (estimated)
- Study completion30 Nov 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (26)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Makerere University, Indiana University, Indian Institute of Science, Mulago Hospital, Uganda
- Responsible party
- Sponsor
- Investigators
- Russell E. Ware, MD, PhD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07708714
- Sponsor's protocol ID
- NOHARM MTD
- Other IDs
- IRB # 2016-8762
- Acronym
- NOHARM MTD
- Status last verified
- Jul 2026
- First submitted
- 13 Jul 2026
- Last updated
- 16 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: NO HARM MTD is a multi-institutional collaboration. It will be necessary to share all study details to determine the results of the study.
Publications
Gupta R, Adekile AD. MRI follow-up and natural history of avascular necrosis of the femoral head in Kuwaiti children with sickle cell disease. J Pediatr Hematol Oncol. 2004 Jun;26(6):351-3. doi: 10.1097/00043426-200406000-00004.
PubMed 15167347Akinyoola AL, Adediran IA, Asaleye CM. Avascular necrosis of the femoral head in sickle cell disease in Nigeria: a retrospective study. Niger Postgrad Med J. 2007 Sep;14(3):217-20.
PubMed 17767206Ndour EHM, Mnika K, Tall FG, Seck M, Ly ID, Nembaware V, Mazandu GK, Sagna Bassene HAT, Dione R, Ndongo AA, Diop JPD, Barry NOK, Djite M, Ndiaye Diallo R, Gueye PM, Diop S, Diagne I, Cisse A, Wonkam A, Lopez Sall P. Biomarkers of sickle cell nephropathy in Senegal. PLoS One. 2022 Nov 21;17(11):e0273745. doi: 10.1371/journal.pone.0273745. eCollection 2022.
PubMed 36409722Ocheke IE, Mohamed S, Okpe ES, Bode-Thomas F, McCullouch MI. Microalbuminuria risks and glomerular filtration in children with sickle cell anaemia in Nigeria. Ital J Pediatr. 2019 Nov 12;45(1):143. doi: 10.1186/s13052-019-0720-0.
PubMed 31718702Mawanda M, Ssenkusu JM, Odiit A, Kiguli S, Muyingo A, Ndugwa C. Micro-albuminuria in Ugandan children with sickle cell anaemia: a cross-sectional study. Ann Trop Paediatr. 2011;31(2):115-21. doi: 10.1179/1465328111Y.0000000013.
PubMed 21575315Jacob M, Saunders DE, Sangeda RZ, Ahmed M, Tutuba H, Kussaga F, Musa B, Mmbando B, Slee AE, Kawadler JM, Makani J, Kirkham FJ. Cerebral Infarcts and Vasculopathy in Tanzanian Children With Sickle Cell Anemia. Pediatr Neurol. 2020 Jun;107:64-70. doi: 10.1016/j.pediatrneurol.2019.12.008. Epub 2019 Dec 27.
PubMed 32111561Munube D, Katabira E, Ndeezi G, Joloba M, Lhatoo S, Sajatovic M, Tumwine JK. Prevalence of stroke in children admitted with sickle cell anaemia to Mulago Hospital. BMC Neurol. 2016 Sep 17;16:175. doi: 10.1186/s12883-016-0704-2.
PubMed 27639979Estepp JH, Smeltzer MP, Wang WC, Hoehn ME, Hankins JS, Aygun B. Protection from sickle cell retinopathy is associated with elevated HbF levels and hydroxycarbamide use in children. Br J Haematol. 2013 May;161(3):402-5. doi: 10.1111/bjh.12238. Epub 2013 Feb 6.
PubMed 23384083Singh SA, Koumbourlis AC, Aygun B. Resolution of chronic hypoxemia in pediatric sickle cell patients after treatment with hydroxyurea. Pediatr Blood Cancer. 2008 Jun;50(6):1258-60. doi: 10.1002/pbc.21480.
PubMed 18293380Nottage KA, Ware RE, Winter B, Smeltzer M, Wang WC, Hankins JS, Dertinger SD, Shulkin B, Aygun B. Predictors of splenic function preservation in children with sickle cell anemia treated with hydroxyurea. Eur J Haematol. 2014 Nov;93(5):377-83. doi: 10.1111/ejh.12361. Epub 2014 Jun 2.
PubMed 24796940Aygun 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 23255310Ware RE, Davis BR, Schultz WH, Brown RC, Aygun B, Sarnaik S, Odame I, Fuh B, George A, Owen W, Luchtman-Jones L, Rogers ZR, Hilliard L, Gauger C, Piccone C, Lee MT, Kwiatkowski JL, Jackson S, Miller ST, Roberts C, Heeney MM, Kalfa TA, Nelson S, Imran H, Nottage K, Alvarez O, Rhodes M, Thompson AA, Rothman JA, Helton KJ, Roberts D, Coleman J, Bonner MJ, Kutlar A, Patel N, Wood J, Piller L, Wei P, Luden J, Mortier NA, Stuber SE, Luban NLC, Cohen AR, Pressel S, Adams RJ. Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial. Lancet. 2016 Feb 13;387(10019):661-670. doi: 10.1016/S0140-6736(15)01041-7. Epub 2015 Dec 6.
PubMed 26670617Nottage KA, Ware RE, Aygun B, Smeltzer M, Kang G, Moen J, Wang WC, Hankins JS, Helton KJ. Hydroxycarbamide treatment and brain MRI/MRA findings in children with sickle cell anaemia. Br J Haematol. 2016 Oct;175(2):331-338. doi: 10.1111/bjh.14235. Epub 2016 Sep 8.
PubMed 27604981Wang WC, Ware RE, Miller ST, Iyer RV, Casella JF, Minniti CP, Rana S, Thornburg CD, Rogers ZR, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik SA, Howard TH, Wynn LW, Kutlar A, Armstrong FD, Files BA, Goldsmith JC, Waclawiw MA, Huang X, Thompson BW; BABY HUG investigators. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011 May 14;377(9778):1663-72. doi: 10.1016/S0140-6736(11)60355-3.
PubMed 21571150Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med. 1995 May 18;332(20):1317-22. doi: 10.1056/NEJM199505183322001.
PubMed 7715639
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimizing Hydroxyurea Therapy in Children With Sickle Cell Anemia In Malaria Endemic Areas: The NOHARM Maximum Tolerated Dose (MTD) Study
- ClinicalTrials.gov ID
- NCT07708714
- Acronym / sponsor ID
- NOHARM MTD / NOHARM MTD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Makerere University, Indiana University, Indian Institute of Science, Mulago Hospital, Uganda
- Study start
- 13 May 2026 (actual)
- Primary completion
- 30 Nov 2030 (estimated)
- Study completion
- 30 Nov 2032 (estimated)
- First posted
- 16 Jul 2026 (actual)
- 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.
NOHARM MTD is an extension of a previous study for children with Sickle Cell Anemia (SCA) who were enrolled in the NOHARM study. All children enrolled in NOHARM received hydroxyurea treatment at a fixed daily dose of 20 mg/kg/day. This dose was selected as a likely safe dose, but does not escalate hydroxyurea to maximum tolerated dose "MTD" as is commonly done in the US. Without this information, we cannot know whether hydroxyurea treatment at the MTD would be feasible (since it requires closer monitoring to avoid hematological toxicities), safe (since adverse events may be greater with MTD, risk of malaria may be altered by MTD, and risk of infections as a result of neutropenia could also be greater with MTD) or beneficial (MTD is associated with higher hemoglobin and fetal hemoglobin concentration).
Detailed description
The purpose of this study is to determine the long-term effects of hydroxyurea treatment on internal organs, the best dosing strategies for children with SCA in Africa, and to identify any genetic factors that affect how a child responds to the study medication. All children in this study will receive the research treatment, hydroxyurea. Hydroxyurea is used to prevent SCA pain episodes and is approved by the European Medicines Agency for adults, adolescents, and children over two-years-old with SCA. During quarterly visits, we will collect information about your child with the study medication, hydroxyurea. This study is being conducted by Dr. Russell Ware at Cincinnati Children's Hospital Medical Center (CCHMC) and his Co-Investigators including Professor Grace Ndeezi and Dr. Phillip Kasirye at the Mulago Hospital Sickle Cell Clinic, and the hydroxyurea medicine is supplied by the manufacturer.
The goal of this clinical trial is to assess the long-term risks and benefits of open-label dose-escalated oral hydroxyurea in a large cohort of Ugandan adolescents with sickle cell anemia (SCA). Additional objectives include investigation of hydroxyurea pharmacokinetics (PK) and pharmacodynamics (PD) in this population, and investigation of the drug's mechanisms of action through advanced genomics and multiomics analysis.
The main questions it aims to answer are:
Aim 1. To determine the safety and efficacy of maximum tolerated dose (MTD) vs. fixed dose (20 mg/kg/day) hydroxyurea treatment in children with SCA in a low-resource, malaria endemic setting. For safety, we will compare adverse events and severe adverse events, including hematologic toxicities. For efficacy, we will assess hemoglobin level, fetal hemoglobin percentage (% HbF), and incidence of vaso-occlusive events such as pain crisis and acute chest syndrome.
Aim 2. To compare the clinical outcomes of MTD vs. fixed dose hydroxyurea treatment in children with SCA in a low-resource, malaria endemic setting. Clinical outcomes assessed will include growth and malaria incidence over a 24-month follow-up period, and differences in renal, splenic, and cerebrovascular function between study entry and 24-month follow-up.
Aim 3. To obtain long-term follow up data to assess laboratory and clinical effects as well as annual visits for organ function (liver, kidneys, spleen, brain) and growth/development.
Aim 4. Quantify the long-term benefits and risks of extended hydroxyurea treatment at MTD. We hypothesize that early and sustained hydroxyurea at MTD can (1) decrease the prevalence of organ damage; (2) improve growth and development; (3) preserve fertility; and (4) maintain a low risk for mutagenic genotoxicity. Protection against organ injury will be assessed in brain (Transcranial Doppler, MRI/MRA, and cerebral oxygenation); heart (echocardiogram); lungs (pulse oximetry, spirometry); kidney (length, glomerular filtration rate, albuminuria, and urine biomarkers); spleen (volume, erythrocyte micronuclei for filtrative function); bones (MRI for avascular necrosis, dual-energy X-ray absorptiometry for bone density); immunological competency (antibody titers to vaccines and malaria exposures); growth and development (standard auxologic measures, Tanner staging, growth hormones); fertility (sex hormones AMH/FSH/LH); and genotoxicity (clonal hematopoiesis, reticulocyte micronuclei).
Aim 5. Define and analyze hydroxyurea pharmacokinetics (PK) and pharmacodynamics (PD) profiles. We hypothesize that PK and PD hydroxyurea profiles will have substantial inter-patient variability. Both the Original Cohort and an untreated Comparator Cohort will undergo formal PK analysis using serial blood samples and a novel point-of-care assay to quantify hydroxyurea levels for calculating PK parameters and optimal dosing. With pharmacometrics analysis, these PK parameters will then be correlated with PD variables, including treatment responses (HbF) and hydroxyurea dose. These PK-PD associations will also be analyzed by age, hydroxyurea dose, and renal function.
Aim 6. Perform genomics analysis for genes influencing hydroxyurea treatment responses and modern multi-omics analysis with proteomics and metabolomics to help elucidate the drug's mechanism of action. We hypothesize that novel genetic variants affect key parameters such as optimal dose and HbF response. In addition to examining known or suspected target genes, we will use a univariate linear mixed model and genome-wide efficient mixed model association to analyze results of unbiased whole exome sequencing and genome-wide array data. We will also perform serial metabolomics and proteomics on samples collected before and during hydroxyurea treatment, to help identify useful biomarkers and signatures of treatment response, and elucidate pathways for hydroxyurea's mechanism of action.
Participants ages 11-16 years old will have information collected for up to 5 years which include:
- Physical Exam and Medical History
- Blood
- Urine Sample
- Near Infrared Spectroscopy
- Transcranial Doppler
- Pharmacokinetics Study
- Echocardiogram
- Spirometry
- Abdominal Ultrasound
- Brain MRI and MRA
- Hip and hand/wrist MRI
- Dual energy X-ray absorptiometry (DEXA)
- Quality of Life
- Physical Exam and Medical History
- Blood Sample
- Hydroxyurea medication
Children will take the maximum tolerated dose of hydroxyurea. A dose determined by pharmacokinetic-guided hydroxyurea initiation and subsequent optimization.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydroxyurea: Original NOHARM Cohort | Experimental | Drug: hydroxycarbamideOriginal Cohort, continue hydroxyurea at optimized dose |
| Hydroxyurea: New Comparator Cohort | Experimental | Drug: hydroxycarbamideNew, untreated cohort, initiate and optimize hydroxyurea dose |
Who may qualify
- Ages
- 11 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hydroxycarbamideHydroxyurea at optimized dose | Drug | Hydroxyurea: New Comparator Cohort, Hydroxyurea: Original NOHARM Cohort |
Primary outcome
Composite measure of organ damage
Time frame: From enrollment, after 24 months and again after 48 months of study treatment.
The primary study endpoint will be a composite measure of organ damage to the brain (defined as ≥2 silent cerebral infarcts on brain MRI or ≥170 cm/sec flow velocities by TCD) or the kidneys (confirmed micro- or macro-albuminuria), or bones (femoral head AVN, Mitchell Stage B or higher).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2026.
- Background: PubMed 15167347Gupta R, Adekile AD. MRI follow-up and natural history of avascular necrosis of the femoral head in Kuwaiti children with sickle cell disease. J Pediatr Hematol Oncol. 2004 Jun;26(6):351-3. doi: 10.1097/00043426-200406000-00004.
- Background: PubMed 17767206Akinyoola AL, Adediran IA, Asaleye CM. Avascular necrosis of the femoral head in sickle cell disease in Nigeria: a retrospective study. Niger Postgrad Med J. 2007 Sep;14(3):217-20.
- Background: PubMed 36409722Ndour EHM, Mnika K, Tall FG, Seck M, Ly ID, Nembaware V, Mazandu GK, Sagna Bassene HAT, Dione R, Ndongo AA, Diop JPD, Barry NOK, Djite M, Ndiaye Diallo R, Gueye PM, Diop S, Diagne I, Cisse A, Wonkam A, Lopez Sall P. Biomarkers of sickle cell nephropathy in Senegal. PLoS One. 2022 Nov 21;17(11):e0273745. doi: 10.1371/journal.pone.0273745. eCollection 2022.
- Background: PubMed 31718702Ocheke IE, Mohamed S, Okpe ES, Bode-Thomas F, McCullouch MI. Microalbuminuria risks and glomerular filtration in children with sickle cell anaemia in Nigeria. Ital J Pediatr. 2019 Nov 12;45(1):143. doi: 10.1186/s13052-019-0720-0.
- Background: PubMed 21575315Mawanda M, Ssenkusu JM, Odiit A, Kiguli S, Muyingo A, Ndugwa C. Micro-albuminuria in Ugandan children with sickle cell anaemia: a cross-sectional study. Ann Trop Paediatr. 2011;31(2):115-21. doi: 10.1179/1465328111Y.0000000013.
- Background: PubMed 32111561Jacob M, Saunders DE, Sangeda RZ, Ahmed M, Tutuba H, Kussaga F, Musa B, Mmbando B, Slee AE, Kawadler JM, Makani J, Kirkham FJ. Cerebral Infarcts and Vasculopathy in Tanzanian Children With Sickle Cell Anemia. Pediatr Neurol. 2020 Jun;107:64-70. doi: 10.1016/j.pediatrneurol.2019.12.008. Epub 2019 Dec 27.
- Background: PubMed 27639979Munube D, Katabira E, Ndeezi G, Joloba M, Lhatoo S, Sajatovic M, Tumwine JK. Prevalence of stroke in children admitted with sickle cell anaemia to Mulago Hospital. BMC Neurol. 2016 Sep 17;16:175. doi: 10.1186/s12883-016-0704-2.
- Background: PubMed 23384083Estepp JH, Smeltzer MP, Wang WC, Hoehn ME, Hankins JS, Aygun B. Protection from sickle cell retinopathy is associated with elevated HbF levels and hydroxycarbamide use in children. Br J Haematol. 2013 May;161(3):402-5. doi: 10.1111/bjh.12238. Epub 2013 Feb 6.
- Background: PubMed 18293380Singh SA, Koumbourlis AC, Aygun B. Resolution of chronic hypoxemia in pediatric sickle cell patients after treatment with hydroxyurea. Pediatr Blood Cancer. 2008 Jun;50(6):1258-60. doi: 10.1002/pbc.21480.
- Background: PubMed 24796940Nottage KA, Ware RE, Winter B, Smeltzer M, Wang WC, Hankins JS, Dertinger SD, Shulkin B, Aygun B. Predictors of splenic function preservation in children with sickle cell anemia treated with hydroxyurea. Eur J Haematol. 2014 Nov;93(5):377-83. doi: 10.1111/ejh.12361. Epub 2014 Jun 2.
- Background: 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.
- Background: PubMed 26670617Ware RE, Davis BR, Schultz WH, Brown RC, Aygun B, Sarnaik S, Odame I, Fuh B, George A, Owen W, Luchtman-Jones L, Rogers ZR, Hilliard L, Gauger C, Piccone C, Lee MT, Kwiatkowski JL, Jackson S, Miller ST, Roberts C, Heeney MM, Kalfa TA, Nelson S, Imran H, Nottage K, Alvarez O, Rhodes M, Thompson AA, Rothman JA, Helton KJ, Roberts D, Coleman J, Bonner MJ, Kutlar A, Patel N, Wood J, Piller L, Wei P, Luden J, Mortier NA, Stuber SE, Luban NLC, Cohen AR, Pressel S, Adams RJ. Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial. Lancet. 2016 Feb 13;387(10019):661-670. doi: 10.1016/S0140-6736(15)01041-7. Epub 2015 Dec 6.
- Individual participant dataSharing planned: Yes. NO HARM MTD is a multi-institutional collaboration. It will be necessary to share all study details to determine the results of the study.
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Sickle Cell Disorders, Sickle Cell Disease
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Investigating the Mechanistic Effects of Mitapivat in Subjects With Sickle Cell Disease
Sickle Cell Anemia, Sickle Cell Thalassemia
Enrolling by invitationPhase 4
A Study to Provide Access to Mitapivat for Participants Who Previously Participated in an Agios-Sponsored Mitapivat Study
Pyruvate Kinase Deficiency, Anemia, Hemolytic
Active, not recruitingPhase 2
A Dose-Finding Study of Tebapivat to Assess Efficacy, and Safety in Participants With Sickle Cell Disease (SCD)
Sickle Cell Disease
RecruitingPhase 3
A Study to Investigate the Effect of Mitapivat on Transfusion Burden in Subjects With Sickle Cell Disease (SCD)
Sickle Cell Disease
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.
Russell E. Ware, MD, PhD principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing hydroxycarbamide in people with Sickle Cell Disease and Sickle Cell Anemia in Children, run by Children's Hospital Medical Center, Cincinnati at 1 site in Uganda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: looking for participants now, as of the sponsor's last update on 16 Jul 2026. 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 Uganda. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Teresa Latham, DrPH, PhD (5138037922, teresa.latham@cchmc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite measure of organ damage (time frame: From enrollment, after 24 months and again after 48 months of study treatment.). 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 NCT07708714, which also lists 26 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 16 Jul 2026.