- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01801423
Sickle Cell Disease - Stroke Prevention in Nigeria Trial (SPIN)
Primary Prevention of Strokes in Nigerian Children With Sickle Cell Disease Affiliated Titles: Sickle Cell Disease - Stroke Prevention in Nigeria (SPIN) Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Kano, Nigeria, P.MB. 3452
- Aminu Kano Teaching Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria for Screening:
- Patients with hemoglobin SS or S beta zero thalassemia confirmed by hemoglobin electrophoresis;
- Informed consent from a parent or legal guardian and assent of participant ages 5 through 12;
- Successful completion of screening procedures: cerebral blood flow velocity ≥ 200 cm/sec in the terminal portion of the middle cerebral artery;
- Patient must be 5 through 12 years of age (i.e., must have attained their 5th but not their 13th birthday when the consent is signed).
Exclusion Criteria for Screening:
- Prior overt stroke (a focal neurological deficit of acute onset) by history, focal neurological deficit on standardized neurological examination, or concern for moderate or severe neurological deficit (which could be due to stroke) based on a positive "10 questions" screening (an established tool in resource poor countries).(2,3) A "positive" screening is defined as answering yes to any one of the 10 questions. The negative predictive value (child does not have moderate or several neurological impairment) of the "10 questions" is greater than 94% in children (2);
- Other exclusions: significant cytopenias [absolute neutrophil count (ANC) <1500/ul, platelets <150,000/ul, reticulocytes <80,000/ul, unless Hb is > 9 g/dl], renal insufficiency (creatinine > 0.8 mg/dl); other significant organ system dysfunction, or other contraindication to hydroxyurea therapy; and history of seizures or diagnosis of epilepsy;
- Patients for whom hydroxyurea therapy is under consideration prior to study consent/education;
- Patients who have previously been treated with hydroxyurea and are being considered to restart hydroxyurea therapy;
- Other significant organ system dysfunction;
- Any other condition or chronic illness, which in the opinion of the site's Principal Investigator (PI) makes participation ill-advised or unsafe.
- Participants of child bearing age who are pregnant or may become pregnant should not take hydroxyurea. If a participant becomes pregnant during the study, their hydroxyurea treatment will be stopped immediately. The onsite will notify the clinical coordinating center and the principal investigators of the case. The site principal investigator and study principal investigators will determine what therapy the participant should receive during pregnancy that is of standard care.
Inclusion Criteria for Study Therapy:
- Successful completion of screening procedures inclusive of cerebral blood flow velocity greater than or equal to 200 cm/sec measured twice or at least one measurement greater than or equal to 220 cm/sec in the terminal portion of the middle cerebral artery or two TCD measurements above 190 cm/sec within a three month interval;
- Informed consent from a parent or legal guardian for study therapy and assent of the participant completed;
- Participant is able to swallow a capsule as observed by study personnel;
- Acceptance of hydroxyurea therapy for one year. After one year of therapy, the participant will have the option to continue therapy with follow up visits to monitor adherence to therapy.
Exclusion Criteria for Treatment Group:
- Unable to commit to follow up visits for the course of the study.
Inclusion Criteria for participants that are not eligible to receive hydroxyurea therapy, but will be followed for one year (control group):
- Successful completion of screening procedures inclusive of cerebral blood flow velocity less than or equal to 199 cm/sec in the terminal portion of the middle cerebral artery;
- Informed consent from a parent or legal guardian and assent from the participant;
- Acceptance to be followed for one year in the study. Hydroxyurea may be given for other reasons as part of the participant's ongoing care, but it will not be given as part of the study.
Exclusion Criteria for the treatment and control groups:
- Unable to commit to follow up visits for the course of the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Hydroxyurea
Study investigators propose to enroll 60 children with SCA and an elevated TCD measurement between 5 and 12 years of age in this one arm feasibility study of hydroxyurea therapy, with follow-up of at least 12 months per subject.
The study intervention will include HU to begin at ~ 20 mg/kg/day(range 17.5 - 26 mg/kg/day).
No dose escalation will occur.
Given the success of the first year of enrollment and the favorable response of TCD measurement after 3 months on HU therapy, the study investigators have participants as an internal pilot.
The definitive phase III trial will now compare low dose HU therapy to the result of no treatment arm from the STOP Trial.
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Hydroxyurea will be prescribed as an investigational therapy by the treating physician.
Recommended guidelines for titration of hydroxyurea to maximal tolerated dose are below.
The study intervention will include hydroxyurea to begin at ~20 mg/kg/day (range 17.5 - 26 mg/kg/day).
No dose escalation will occur as this dose was shown to have some efficacy in infants with SCA and was associated with rare myelosuppression.(1)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Hydroxyurea Therapy Acceptance and Adherence
Time Frame: 5 years
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The primary outcome measure will be adherence to daily administration of hydroxyurea.
If adherence rate is less than 55%, alternative strategies must be considered for the definitive Phase III Trial.
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5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Hydroxyurea Safety protocol for Children with Sickle Cell Anemia
Time Frame: 12 Months
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Study investigators will evaluate the use of a standard safety protocol, non-dose escalating, for hydroxyurea in children with sickle cell anemia using a protocol similar to the recently completed National Heart Lung and Blood Institute (NHLBI) Baby HUG study, published in Lancet.(1)
Study investigators expect the proportion of serious adverse reactions, as well as hydroxyurea-related morbidity and mortality, to be very small compared to the benefits.
Study investigators will compare the frequency of severe adverse events and hydroxyurea toxicity related events that are associated with hospitalization in those receiving hydroxyurea (n= 60) to those who had normal transcranial Doppler measurements (n= 210) over the course of one year.
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12 Months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Feasibility of a Definitive Phase III Trial for Hydroxyurea Therapy to Prevent Strokes in Sickle Cell Disease
Time Frame: 24 Months
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During the course of the current study, study investigators will prepare a manual of operations and case report forms for the proposed trial.
Investigators will also solidify working relationships with our colleagues and collaborators at Aminu Kano Teaching Hospital in Kano, Nigeria; and develop and organize all committees, collaborators and study procedures necessary for initiation of a successful, definitive, Phase III Trial.
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24 Months
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Michael R. DeBaun, MD, MPH, Vanderbilt University
- Principal Investigator: Muktar Aliyu, MBBS, MPH, DrPH, Vanderbilt University
- Principal Investigator: Lori Jordan, MD, PhD, Vanderbilt University
Publications and helpful links
General Publications
- Wang 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.
- Mung'ala-Odera V, Meehan R, Njuguna P, Mturi N, Alcock K, Carter JA, Newton CR. Validity and reliability of the 'Ten Questions' questionnaire for detecting moderate to severe neurological impairment in children aged 6-9 years in rural Kenya. Neuroepidemiology. 2004 Jan-Apr;23(1-2):67-72. doi: 10.1159/000073977.
- Mung'ala-Odera V, Newton CR. Identifying children with neurological impairment and disability in resource-poor countries. Child Care Health Dev. 2007 May;33(3):249-56. doi: 10.1111/j.1365-2214.2006.00714.x.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Hematologic Diseases
- Genetic Diseases, Inborn
- Anemia
- Anemia, Hemolytic, Congenital
- Anemia, Hemolytic
- Hemoglobinopathies
- Stroke
- Anemia, Sickle Cell
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antineoplastic Agents
- Antisickling Agents
- Hydroxyurea
Other Study ID Numbers
- 1R01NS094041-01 (U.S. NIH Grant/Contract)
- 1R21NS080639-01 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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