Risk Clinical Stratification of Sickle Cell Disease in Nigeria, Assessment of Efficacy/Safety of Hydroxyurea Treatment

March 7, 2023 updated by: Bamidele Tayo, Loyola University

Risk Stratification for Clinical Severity of Sickle Cell Disease in Nigeria and Assessment of Efficacy and Safety During Treatment With Hydroxyurea

The vast majority of births with sickle cell disease (SCD) occur in Africa and 90% are thought to die before the age of five. Hydroxyurea (HU) is the only drug approved by the FDA for the treatment of sickle cell anemia. Although HU is used to treat small numbers of patients in Africa, cost, fear of toxicity, and lack of awareness and availability limit its use. The leukopenia that may be seen with HU raises the possibility of increased susceptibility to infection. Risk stratification - i.e., identification of patients most likely to benefit- could focus therapy and provide confidence that the risk:benefit ratio is favorable. Several clinical measures of future risk are well defined and findings on modifier genes in the US, primarily related to fetal hemoglobin (HbF), have further improved risk prediction. Whether the genetic variants predict severity in Africa is not known. The investigators have established a SCD cohort in Ibadan, Nigeria. In the first phase of this research the investigators will implement clinical risk examinations and assess the relationship between clinical characteristics (including levels of HbF) and known genetic markers. As a proxy for a birth cohort, the investigators will compare the frequency of the genetic markers in adult patients (i.e., "survivors") to children. In the second phase the investigators will randomize 40 high risk adult patients to fixed low dose HU or no HU treatment in a crossover design and monitor hematologic and physiologic parameters to document hematologic effects and safety. This work will lay the basis for a large-scale trial to document safety and efficacy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

53

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Nigeria
    • Oyo State
      • Ibadan, Oyo State, Nigeria
        • University of Ibadan College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age >= 18 years
  • HemoglobinSS (HbSS) or beta-zero (B0) thalassemia genotype
  • Hemoglobin concentration >4.5 g/dL at steady state and time of enrollment
  • Absolute neutrophil count >1,500/mircoliter
  • Platelet count >95,000/microliter
  • Serum creatinine <1.2 mg/dL
  • Alanine transaminase less than two times the upper limit of normal

Exclusion Criteria:

  • HIVpositive
  • Hepatitis B and/or C positive

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: hydroxyurea
500mg of hydroxyurea/day during 6 months
Drug: hydroxyurea
Other Names:
  • Hydroxycarbamide
No Intervention: No treatment
No hydroxyurea treatment during 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cytopenia
Time Frame: every 2 weeks during a period of 6 months
Neutrophil count <500/microliter, platelet count <50,000 or a reticulocyte count<95,000 with Hemoglobin of 9.0 g/dL
every 2 weeks during a period of 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Development of infection evaluated by a physician at the point of care
Time Frame: every 2 weeks for period of 6 months
Infections such as malaria or tuberculosis, which may be newly acquired or recrudescent.
every 2 weeks for period of 6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
laboratory values of Hemoglobin F%, hemoglobin concentration, reticulocyte count, mean corpuscular volume and white blood cell count.
Time Frame: baseline, 3 months and 6 months.
baseline, 3 months and 6 months.
Clinical complications such as acute pain episode, acute chest syndrome and need for blood transfusion.
Time Frame: every 2 weeks for a period of 6 months.
Evaluated by a nurse or physician at point of care.
every 2 weeks for a period of 6 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Loyola University

Collaborators

University of Illinois at Chicago
University of Ibadan

Investigators

  • Principal Investigator: Bamidele O Tayo, PhD, Loyola University Chicago
  • Principal Investigator: Victor R Gordeuk, MD, University of Illinois at Chicago
  • Principal Investigator: Titilola S Akingbola, MBBS, FWACP, University of Ibadan College of Medicine, Nigeria
  • Principal Investigator: Richard S Cooper, MD, Loyola University Chicago
  • Principal Investigator: Lewis Hsu, MD, University of Illinois at Chicago

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2014

Primary Completion (Actual)

September 1, 2017

Study Completion (Actual)

December 1, 2022

Study Registration Dates

First Submitted

March 24, 2014

First Submitted That Met QC Criteria

May 28, 2014

First Posted (Estimate)

May 29, 2014

Study Record Updates

Last Update Posted (Estimate)

March 9, 2023

Last Update Submitted That Met QC Criteria

March 7, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 205449

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: PR00007593
    Information comments: De-identified and anonymized IPD can be requested at http://doi.org/10.25934/PR00007593

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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