Vincent Mboizi, Catherine Nabaggala, Deogratias Munube, John M Ssenkusu, Phillip Kasirye, Samson Kamya, Michael G Kawooya, Amelia Boehme, Frank Minja, Ezekiel Mupere, Robert Opoka, Caterina Rosano, Richard Idro, Nancy S Green
{"title":"羟基脲治疗乌干达儿童镰状细胞性贫血的神经和认知保护（BRAIN SAFE II）：单臂开放标签试验方案。","authors":"Vincent Mboizi, Catherine Nabaggala, Deogratias Munube, John M Ssenkusu, Phillip Kasirye, Samson Kamya, Michael G Kawooya, Amelia Boehme, Frank Minja, Ezekiel Mupere, Robert Opoka, Caterina Rosano, Richard Idro, Nancy S Green","doi":"10.1016/j.conctc.2024.101404","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Children with sickle cell anemia (SCA) in Sub-Saharan Africa are at high risk of sickle cerebrovascular injury (SCVI). Hydroxyurea, a commonly used disease-modifying therapy, may reduce SCVI resulting in potential impact on reducing stroke and cognitive dysfunction. We aim to test the impact of daily hydroxyurea therapy on these outcomes in Ugandan children with SCA. We hypothesized that hydroxyurea therapy over 36 months will prevent, stabilize or improve these complications of SCA.</p><p><strong>Methods: </strong>The BRAIN SAFE II study is an open label, single arm trial of daily hydroxyurea in 270 children with SCA (HbSS) in Uganda, ages 3-9 years. Following baseline assessments, participants began hydroxyurea therapy and are followed according to local guidelines. Standard hydroxyurea dose is escalated to maximum tolerated dose (MTD). SCVI is assessed by cerebral arterial velocity using Doppler ultrasound, with cognitive function determined by formal neurocognitive testing (primary outcomes). Structural SCVI is assessed by magnetic resonance imaging (MRI) and angiography (MRA) in a sub-sample of 90 participants ages >5 years. At trial midpoint (18 months) and completion (36 months), outcomes of age-specific assessments will be compared to baseline, as well as biomarkers of anemia, inflammation and malnutrition (secondary outcomes) to determine their relationships to primary outcomes.</p><p><strong>Conclusion: </strong>This trial will examine the impact of hydroxyurea on preventing or ameliorating SCA SCVI in children, assessed by reducing incident stroke, stroke risk and neurocognitive dysfunction. Trial results will provide critical insight into the role of hydroxyurea therapy on critical manifestations of SCVI in children with SCA.</p><p><strong>Trial registration: </strong>https://clinicaltrials.gov/ct2/show/NCT04750707 (registered 11 February 2021).</p><p><strong>Protocol version: </strong>BRAIN SAFE II Protocol Version 3.0, Mar 02, 2022.</p>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"42 ","pages":"101404"},"PeriodicalIF":1.4000,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664125/pdf/","citationCount":"0","resultStr":"{\"title\":\"Hydroxyurea therapy for neurological and cognitive protection in pediatric sickle cell anemia in Uganda (BRAIN SAFE II): Protocol for a single-arm open label trial.\",\"authors\":\"Vincent Mboizi, Catherine Nabaggala, Deogratias Munube, John M Ssenkusu, Phillip Kasirye, Samson Kamya, Michael G Kawooya, Amelia Boehme, Frank Minja, Ezekiel Mupere, Robert Opoka, Caterina Rosano, Richard Idro, Nancy S Green\",\"doi\":\"10.1016/j.conctc.2024.101404\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Children with sickle cell anemia (SCA) in Sub-Saharan Africa are at high risk of sickle cerebrovascular injury (SCVI). Hydroxyurea, a commonly used disease-modifying therapy, may reduce SCVI resulting in potential impact on reducing stroke and cognitive dysfunction. We aim to test the impact of daily hydroxyurea therapy on these outcomes in Ugandan children with SCA. We hypothesized that hydroxyurea therapy over 36 months will prevent, stabilize or improve these complications of SCA.</p><p><strong>Methods: </strong>The BRAIN SAFE II study is an open label, single arm trial of daily hydroxyurea in 270 children with SCA (HbSS) in Uganda, ages 3-9 years. Following baseline assessments, participants began hydroxyurea therapy and are followed according to local guidelines. Standard hydroxyurea dose is escalated to maximum tolerated dose (MTD). SCVI is assessed by cerebral arterial velocity using Doppler ultrasound, with cognitive function determined by formal neurocognitive testing (primary outcomes). Structural SCVI is assessed by magnetic resonance imaging (MRI) and angiography (MRA) in a sub-sample of 90 participants ages >5 years. At trial midpoint (18 months) and completion (36 months), outcomes of age-specific assessments will be compared to baseline, as well as biomarkers of anemia, inflammation and malnutrition (secondary outcomes) to determine their relationships to primary outcomes.</p><p><strong>Conclusion: </strong>This trial will examine the impact of hydroxyurea on preventing or ameliorating SCA SCVI in children, assessed by reducing incident stroke, stroke risk and neurocognitive dysfunction. Trial results will provide critical insight into the role of hydroxyurea therapy on critical manifestations of SCVI in children with SCA.</p><p><strong>Trial registration: </strong>https://clinicaltrials.gov/ct2/show/NCT04750707 (registered 11 February 2021).</p><p><strong>Protocol version: </strong>BRAIN SAFE II Protocol Version 3.0, Mar 02, 2022.</p>\",\"PeriodicalId\":37937,\"journal\":{\"name\":\"Contemporary Clinical Trials Communications\",\"volume\":\"42 \",\"pages\":\"101404\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2024-11-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664125/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Contemporary Clinical Trials Communications\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.conctc.2024.101404\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q4\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Contemporary Clinical Trials Communications","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.conctc.2024.101404","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Hydroxyurea therapy for neurological and cognitive protection in pediatric sickle cell anemia in Uganda (BRAIN SAFE II): Protocol for a single-arm open label trial.
Background: Children with sickle cell anemia (SCA) in Sub-Saharan Africa are at high risk of sickle cerebrovascular injury (SCVI). Hydroxyurea, a commonly used disease-modifying therapy, may reduce SCVI resulting in potential impact on reducing stroke and cognitive dysfunction. We aim to test the impact of daily hydroxyurea therapy on these outcomes in Ugandan children with SCA. We hypothesized that hydroxyurea therapy over 36 months will prevent, stabilize or improve these complications of SCA.
Methods: The BRAIN SAFE II study is an open label, single arm trial of daily hydroxyurea in 270 children with SCA (HbSS) in Uganda, ages 3-9 years. Following baseline assessments, participants began hydroxyurea therapy and are followed according to local guidelines. Standard hydroxyurea dose is escalated to maximum tolerated dose (MTD). SCVI is assessed by cerebral arterial velocity using Doppler ultrasound, with cognitive function determined by formal neurocognitive testing (primary outcomes). Structural SCVI is assessed by magnetic resonance imaging (MRI) and angiography (MRA) in a sub-sample of 90 participants ages >5 years. At trial midpoint (18 months) and completion (36 months), outcomes of age-specific assessments will be compared to baseline, as well as biomarkers of anemia, inflammation and malnutrition (secondary outcomes) to determine their relationships to primary outcomes.
Conclusion: This trial will examine the impact of hydroxyurea on preventing or ameliorating SCA SCVI in children, assessed by reducing incident stroke, stroke risk and neurocognitive dysfunction. Trial results will provide critical insight into the role of hydroxyurea therapy on critical manifestations of SCVI in children with SCA.
Trial registration: https://clinicaltrials.gov/ct2/show/NCT04750707 (registered 11 February 2021).
Protocol version: BRAIN SAFE II Protocol Version 3.0, Mar 02, 2022.
期刊介绍：
Contemporary Clinical Trials Communications is an international peer reviewed open access journal that publishes articles pertaining to all aspects of clinical trials, including, but not limited to, design, conduct, analysis, regulation and ethics. Manuscripts submitted should appeal to a readership drawn from a wide range of disciplines including medicine, life science, pharmaceutical science, biostatistics, epidemiology, computer science, management science, behavioral science, and bioethics. Contemporary Clinical Trials Communications is unique in that it is outside the confines of disease specifications, and it strives to increase the transparency of medical research and reduce publication bias by publishing scientifically valid original research findings irrespective of their perceived importance, significance or impact. Both randomized and non-randomized trials are within the scope of the Journal. Some common topics include trial design rationale and methods, operational methodologies and challenges, and positive and negative trial results. In addition to original research, the Journal also welcomes other types of communications including, but are not limited to, methodology reviews, perspectives and discussions. Through timely dissemination of advances in clinical trials, the goal of Contemporary Clinical Trials Communications is to serve as a platform to enhance the communication and collaboration within the global clinical trials community that ultimately advances this field of research for the benefit of patients.
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