Hydroxyurea Optimisation in Sickle Cell Disease

NCT07543289 | Not Yet Recruiting

• 1 other identifier: ERC/2024/07/12
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The wide interindividual variability in clinical response to hydroxyurea therapy in the management of sickle cell disease has limited its use. These variabilities have been linked to differences in pharmacodynamics, pharmacokinetics, and pharmacogenetics. This study, therefore, aims to enhance understanding of these factors as they relate to hydroxyurea therapy, with the overall goal of developing a precision medicine algorithm. The study will be a prospective cohort pharmacokinetic study of 100 Nigerian patients with sickle cell disease, including current hydroxyurea users and naive patients. Pharmacodynamic markers will be collected to evaluate response. PopPK and PK-PD models will be developed in Monolix, exposure-response relationships will be analysed in R, and pregnancy, lactation, and paediatrics PBPK models will be developed in Simcyp or PK-SIM to inform dose optimisation. This study aims to build a pharmacometric model by integrating differences in pharmacokinetics, pharmacodynamics, and pharmacogenetics of hydroxyurea, which could aid the optimisation of hydroxyurea for sickle cell patients in Nigeria. The objectives of the study are i. To determine the prevalence of genetic polymorphisms in metabolic enzymes and transporters relevant to the disposition of hydroxyurea in the Nigerian sickle cell disease population, ii. To develop and validate an analytical method for the quantification of hydroxyurea using high-performance liquid chromatography. iii. To evaluate the influence of genetic and other covariates on hydroxyurea disposition in the Nigerian sickle cell disease population using population pharmacokinetic modelling, iv. To investigate the relationship between hydroxyurea exposure and clinical outcomes (foetal haemoglobin, mean corpuscular volume, reduction in vaso-occlusive crises (VOC), and improved blood count) using pharmacokinetic-pharmacodynamic modelling, v. To develop physiologically-based pharmacokinetic (PBPK) models that could predict hydroxyurea concentrations in special populations of sickle cell disease patients in Nigeria i.e. pregnant women, lactating mothers, breastfed infants, and paediatrics. vi. To develop a dosing guideline for hydroxyurea therapy in Nigerian sickle cell patients. Overall, this study will provide scientific knowledge that can enhance clinical decision-making in sickle cell management within the Nigerian population, and the models could serve as a template to optimize hydroxyurea use in this population.

Conditions

Sickle Cell Disease

Keywords

Modelling; Genetic Polymorphism; Pharmacokinetics; Clinical Outcomes; Hydroxyurea; Pharmacogenetics

Outcome Measures

Primary Outcomes (1)

• Increase in foetal haemoglobin

  Hydroxyurea exerts its therapeutic effects primarily through the induction of foetal haemoglobin production, thereby inhibiting the polymerization of sickled haemoglobin and ameliorating the pathophysiological sequelae of sickle cell disease. By inhibiting ribonucleotide reductase, hydroxyurea interferes with DNA synthesis, prompting the differentiation of erythroid progenitors into red cells containing elevated levels of foetal haemoglobin.

  6 months

Secondary Outcomes (1)

• Reduction in frequency of vaso-occlusive crises

  6 months

Interventions

Hydroxyurea (HU) DRUG

All study participants are sickle cell disease patients who are currently on hydroxyurea therapy or who would be willing to commence hydroxyurea therapy.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study population for this research comprises patients diagnosed with sickle cell disease (SCD) of Nigerian descent, recruited from selected clinical centres within Nigeria ( Sickle Cell Foundation, Ibadan and the Obafemi Awolowo University Teaching Hospital Complex). They will be consented SCD adult patients who have been on hydroxyurea at least six months before study commencement or who are willing to commence hydroxyurea therapy. In both instances, they will be SCD patients whose genetic profile for the major metabolising enzymes are known.

You may qualify if:

• Patients with confirmed diagnosis of sickle cell disease (SCD) (e.g., HbSS, HbSC) and of Nigerian descent.
• Patients currently on hydroxyurea therapy or hydroxyurea-naive patients who are willing to commence hydroxyurea therapy.
• Patients whose genotypic profile for the major metabolising enzymes has been previously done e.g. CYP2D6.
• Patients who consent to be part of the study

You may not qualify if:

• Patients with severe comorbidities that may significantly alter pharmacokinetics (e.g., advanced renal or hepatic failure)
• Patients in acute crisis at the time of sampling.
• Patients with documented poor adherence to other medications previously on.
• Pregnant females and lactating mothers.

Sponsors & Collaborators

• Ochuko Orherhe: lead
• Consortium for Advanced Research Training in Africa (CARTA): collaborator
• Obafemi Awolowo University: collaborator
• Obafemi Awolowo University Teaching Hospital: collaborator

Study Sites (1)

Obafemi Awolowo University Teaching Hospital Complex

Ile-Ife, Osun State, 220282, Nigeria

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples will be obtained from whole blood samples collected from study participants. This will be retained for the duration of the study.

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Central Study Contacts

Ochuko M. Orherhe, M.Phil.

CONTACT

+2348051589453; oorherhe@oauife.edu.ng

Babatunde A Adeagbo, PhD

CONTACT

+2348069019643; badeagbo@oauife.edu.ng

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Miss

Study Record Dates

• First Submitted: April 15, 2026
• First Posted: April 21, 2026
• Study Start: May 8, 2026
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

NG (1)