Crossover Study of an Oral Treatment for Sickle Cell Disease

ABSTRACT Sickle cell disease SCD affects approximately people in the United States and millions worldwide Symptoms appear shortly after birth and in less developed countries the majority of children with SCD die before the age of five In the U S SCD patients suffer chronic pain and fatigue severe acute painful crises requiring hospitalization and opiates strokes and multi organ damage and have an average mortality in their s The only FDA approved drug for adults with SCD is the anticancer drug hydroxyurea New treatments are desperately needed for both children and adults with SCD SCD is a botanical drug that has shown direct in vitro and in vivo anti sickling activity Our goal is to develop SCD as a safe and effective oral treatment that prevents the inexorable progression of sickle cell disease in children and adults In sub Saharan Africa and India where many millions suffer with sickle cell disease of the population depends on Traditional Medicine botanicals for primary health care Therefore SCD as a botanical drug is the solution for the millions with sickle cell disease worldwide We recently completed a day repeat oral dose dose escalation study of SCD in adults with sickle cell disease The Phase b results showed that SCD was safe and well tolerated and established the dose and schedule to be used in a Phase study At the two highest doses there was a profound effect on reducing fatigue and pain the two most common symptoms of SCD Building on the results of our Phase b study we propose a double blind placebo controlled x crossover study in patients with homozygous S S sickle cell disease to establish the clinically relevant endpoints to be used in a Phase and Phase study A crossover study where each subject is his or her own control doubles the effective sample size so the crossover study has the equivalent power of a patient parallel design The proposed crossover study has sufficient power to show a statistically significant and clinically relevant improvement in fatigue based our Phase b results and may show a statistically significant and clinically relevant improvement in pain The crossover study will also measure the effect of SCD on sleep red blood cell RBC hemolysis markers inflammatory cytokines and circulating sickled cells in venous whole blood Project Narrative About Americans have Sickle Cell Disease Those affected often have high medical costs a poor quality of life and early death Treatment options are few There is a substantial unmet medical need for new safe and effective disease modifying drugs like the one in this grant to treat this disease