Clinical Trials Logo

Clinical Trial Summary

Background: Sickle cell disease (SCD) is an inherited blood disorder. The disease affects the ability of red blood cells to carry oxygen; this in turn can injure organs including the heart, lungs, and kidneys. SCD can lead to serious illness and death. Treatments such as bone marrow transplants and gene therapies can cure SCD, but they are not widely available. Current drug treatments for SCD are not always effective. This natural history study will examine how a study drug (mitapivat) affects red blood cells in people with SCD. Objective: To learn how mitapivat affects red blood cells in people with SCD. Eligibility: People with SCD who are enrolled in the parent study, NIH protocol IRB001565-H. Design: Procedures for this study will be done during visits already scheduled for the parent study. Participants will have additional blood drawn during study visits. The additional amount will be about 3.5 teaspoons. Participants will undergo a test called near infrared spectroscopy (NIRS) up to 9 times. Probes will be placed on their skin. A blood pressure cuff will be placed on their arm. The cuff will be filled with air for up to 5 minutes and then released. Participants may be asked to breathe at a certain rate or to hold their breath during these measurements. NIRS measures oxygen levels, blood flow, and the makeup of skin and muscle. Researchers will draw additional information for this study from participants medical records.


Clinical Trial Description

Study Description: Subjects actively enrolled protocol AG348-C-020 (NIH protocol IRB001565-H), an industry-sponsored phase 2/3 study investigating the efficacy of mitapivat in treating sickle cell disease (SCD), will be invited to participate in this protocol simultaneously to further investigate the mechanistic effects of mitapivat. Subjects will be asked for a blood sample at specified time points before and after starting on mitapivat and to undergo near infrared spectroscopy (NIRS) testing to investigate the mechanisms of action of mitapivat in subjects with SCD. Objectives: To evaluate the mechanisms of action of mitapivat in subjects with SCD. Endpoints: PRIMARY ENDPOINT: The percentage change in the oxygen affinity measure p50 (defined as the partial pressure of oxygen at which Hb is 50% saturated with oxygen) between baseline and the average value at 12, 24 and 52 weeks. This change will be compared between the placebo and mitapivat arms. SECONDARY ENDPOINTS: - The p50 changes will also be assessed at the individual time points of 12, 24, and 52 weeks and compared between arms. - Percentage of sickled cells and time to 50% sickling (t50) under normal and hypoxic ex vivo conditions at regular time intervals on mitapivat and percentage change from baseline to the individual time points at 12, 24, and 52 weeks . This change will be compared between the placebo and mitapivat arms. - Percentage change in intracellular reactive oxidative species (ROS) in red blood cells (RBCs) using a ROS sensitive fluorescent probe and mass spectrometry- based proteomics of RBC lysates between baseline and the individual time points at 12, 24, and 52 weeks. This change will be compared between the placebo and mitapivat arms. The percentage change in phosphatidylserine (PS) externalization using annexin V labeling (marker of red cell survival) by flow cytometry between baseline and the individual time points at 12, 24, and 52 weeks. This change will be compared between the placebo and mitapivat arms. - Percentage change in muscle physiology, tissue oxygenation and blood flow using NIRS methodologies between baseline the individual time points at 12, 24, 52, and 59 weeks. This change will be compared between the placebo and mitapivat arms. - RBC deformability and sickling using osmotic and oxygen gradient ektacytometry. TERTIARY/EXPLORATORY ENDPOINTS: - Evaluate effect of mitapivat on RBC metabolomics and proteomics between baseline and various follow-up periods. This change will be compared between the placebo and mitapivat arms. - Measurement of glycated Hb S level as a surrogate measure for red cell half-life between baseline and various follow-up periods. This change will be compared between the placebo and mitapivat arms. - Evaluate effect of mitapivat on RBC band 3 tyrosine phosphorylation between baseline and various follow-up periods. This change will be compared between the placebo and mitapivat arms. - Correlation between potential exploratory biomarkers and clinical laboratory parameters. - Evaluate change in cerebral hemodynamic measurements through magnetic resonance imaging (MRI) for cerebral blood flow, oxygen extraction fraction, and cerebral metabolic rate of oxygen consumption from baseline, at 12 weeks, 52, and 59 weeks. This change will be compared between the placebo and mitapivat arms. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05675436
Study type Observational
Source National Institutes of Health Clinical Center (CC)
Contact
Status Enrolling by invitation
Phase
Start date May 9, 2024
Completion date October 27, 2027

See also
  Status Clinical Trial Phase
Completed NCT04134299 - To Assess Safety, Tolerability and Physiological Effects on Structure and Function of AXA4010 in Subjects With Sickle Cell Disease N/A
Completed NCT04581356 - Voxelotor Sickle Cell Exercise Study Phase 4
Completed NCT02712346 - The Role of Endothelin-1 in Sickle Cell Disease Phase 1
Completed NCT01976416 - Novel Use Of Hydroxyurea in an African Region With Malaria Phase 3
Withdrawn NCT02162225 - Study of Beet Juice for Patients With Sickle Cell Anemia Phase 2
Completed NCT01137721 - State Of The Art Functional Imaging In Sickle Cell Disease
Withdrawn NCT00937144 - Endothelial Function in Patients With Sickle Cell Anemia Before and After Sildenafil Phase 4
Terminated NCT01350232 - Treatment of Sickle Cell Anemia With Stem Cell Transplant N/A
Completed NCT00512564 - Clinical and Laboratory Assessment of Iron Overload in Sickle Cell Anemia and Sickle Cell Thalassemia N/A
Completed NCT00512226 - Iron Overload Assesment in Sickle Cell Anemia and Sickle Cell Thalassemia N/A
Completed NCT00004143 - Allogeneic Mixed Chimerism Stem Cell Transplant Using Campath for Hemoglobinopathies & Bone Marrow Failure Syndromes Phase 2
Completed NCT00004412 - Phase II Randomized Trial:Arginine Butyrate Plus Standard Local Therapy in Patients With Refractory Sickle Cell Ulcers Phase 2
Withdrawn NCT01925001 - Phase 2 Study of MP4CO to Treat Vaso-occlusive Sickle Crisis Phase 2
Completed NCT01848691 - Carbon Monoxide Monitor for the Measurement of End-Tidal Carbon Monoxide Levels in Children With or Without Hemolysis N/A
Completed NCT01783990 - Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) Follow-up Observational Study II Protocol
Completed NCT01000155 - Efficacy of Vorinostat to Induce Fetal Hemoglobin in Sickle Cell Disease Phase 2
Completed NCT00874172 - Effectiveness of New Analgesic Strategy Compared to the Usal Antalgic Strategy N/A
Completed NCT00236093 - Extension Study of ACTIQ Treatment for Children and Adolescents With Breakthrough Pain Phase 2
Completed NCT00399074 - Sulfadoxine- Pyrimethamine Versus Weekly Chloroquine for Malaria Prevention in Children With Sickle Cell Anemia Phase 3
Completed NCT00004492 - Phase I/II Randomized Study of Hydroxyurea With or Without Clotrimazole in Patients With Sickle Cell Anemia Phase 1/Phase 2