Background: Sickle cell disease (SCD) is an inherited blood disorder. The disease affects the ability of red blood cells to carry oxygen. Research has shown that curcumin, a natural compound found in turmeric, can improve the health of red blood cells in people with SCD. But the body cannot absorb curcumin well when it is taken by mouth. Researchers want to know if a skin gel (VAS-101) can help the body better absorb curcumin. VAS-101 contains curcumin, which comes from turmeric. Objective: To test VAS-101 in people with stable SCD. Eligibility: People aged 18 to 70 years with stable SCD. Design: People who want to join the study will be screened with physical exam with blood tests to see if they are eligible. If they qualify, they can enroll in the study. Participants will have up to 15 clinic visits over about 14 weeks. Some may need to stay overnight in the hospital for up to 2 days to make it easier to collect blood samples after the gel is applied. For 6 weeks, a special gel called VAS-101 will be put on the forearms in the clinic two times a week. Staff will rub the gel into the skin for at least 30 seconds using a soft toothbrush. The area stays uncovered for at least 10 minutes, then is covered with a bandage or sleeve. After 24 hours, the dressing can be removed and the skin can be washed. Some visits will include blood tests and other exams. On three visits, a test called near infrared spectroscopy (NIRS) will be done. For this test, probes are placed on the skin to measure blood flow, oxygen levels, and the makeup of skin and muscle. A blood pressure cuff is used to squeeze the arm for up to 5 minutes. The last clinic visit will happen about 4 weeks after the final gel application....
Study Description: The overall objective of this study is to assess the clinical safety and tolerability of a patented, bioavailability-enhanced, transdermal application of curcuminoids, VAS-101 / Vasceptor(R) (8.5% curcuminoids transdermal gel), in subjects with stable sickle cell disease (SCD). VAS-101 contains Curcugen(R) as the active ingredient, with concentrations of 2mg in VAS-101 0.05 mL, 4mg in VAS-101 0.1 mL, and 12mg in VAS-101 0.3 mL. Subjects enrolled will receive 0.2 mL of VAS-101 topically twice weekly for two weeks, followed by 0.4 mL twice weekly for two weeks, then 0.6mL twice weekly for two weeks. Throughout the course of the study, subjects will be monitored for signs and symptoms of adverse events. The effect of VAS-101 on laboratory biomarkers of inflammatory activity, red cell metabolism and deformability will also be studied at specific timepoints. Objectives: Primary Objective: To assess the clinical safety and tolerability of escalating doses of a patented, bioavailability-enhanced, transdermal application of curcuminoids, VAS-101 / Vasceptor(R) (8.5% curcuminoids transdermal gel), in adult patients with stable SCD. Secondary Objectives: To assess the pharmacokinetics of VAS-101 in SCD and correlate drug exposure to anti-inflammatory and anti-sickling effects at different dose levels. Tertiary/Exploratory Objectives: To explore effects of VAS-101 on neutrophil and platelet function, red cell and monocyte metabolism, and muscle physiology. Endpoints: Primary Endpoints: * To evaluate the safety and tolerability of VAS-101 as assessed by: --The type, incidence, severity, and relationship to study treatment of AEs and serious adverse events (SAEs) from Baseline to Day 66, including: * Number of most common treatment related adverse events * Number of serious adverse events possibly related to treatment * Number of discontinuations due to AEs from Baseline to Day 66 * Mean change in clinical laboratory test results (e.g., serum chemistry, liver function test, hematology, coagulation) from baseline at each dose level (days 0, 14, 28, 42 and 66). Secondary Endpoints: * Percentage of sickled cells, time to 50 percent sickling (t50) and area under sickling curve under hypoxic ex vivo conditions at regular time intervals (days 0, 14, 28, 42 and 66). * Percentage change in oxygen affinity (p50) at regular time intervals (days 0, 14, 28, 42 and 66). * Change in intracellular reactive oxidative species (ROS) in RBCs at regular time intervals (days 0, 14, 28, 42 and 66). * Change in markers of inflammation, adhesion and coagulation activation at regular time intervals (days 0, 14, 28, 42 and 66). Tertiary/Exploratory Endpoints: * Proteomic, metabolomic and lipidomic studies to evaluate the effect of VAS-101 on RBCs and monocytes at regular time intervals (days 0, 14, 28, 42 and 66). * Evaluate effect of VAS-101 on RBC band 3 tyrosine phosphorylation at regular time intervals (days 0, 14, 28, 42 and 66). * Assessment of muscle physiology, tissue oxygenation and blood flow using near infrared spectroscopy (NIRS) methodologies at regular time intervals (days 0, 42 and 66). * Evaluate effect of VAS-101 on neutrophil activation and neutrophil extracellular trap (NET) formation at baseline and regular time intervals (days 0, 14, 28, 42 and 66). * Studies of extracellular vesicles (EVs) at regular time intervals (days 0, 14, 28, 42 and 66).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
25
VAS-101 contains Curcugen (Registered Trademark) as the active ingredient, with concentrations of 2mg in VAS-101 0.05 mL, 4mg in VAS-101 0.1 mL, and 12mg in VAS-101 0.3 mL
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
RECRUITINGTo assess the clinical safety and tolerability of escalating doses of a patented, bioavailability-enhanced, transdermal application of curcuminoids, VAS-101 / Vasceptor (8.5% curcuminoids transdermal gel), in adult patients with stable SCD.
-To evaluate the safety and tolerability of VAS-101 as assessed by:-The type, incidence, severity, and relationship to study treatment of AEs and serious adverse events (SAEs) from Baseline to Day 66, including:-Number of most common treatment related adverse events-Number of serious adverse events possibly related to treatment-Number of discontinuations due to AEs from Baseline to Day 66-Mean change in clinical laboratory test results (e.g., serum chemistry, liver function test, hematology, coagulation) from baseline at each dose level (days 0, 14, 28, 42 \& 66).
Time frame: Baseline to Day 66
To assess the pharmacokinetics of VAS-101 in SCD and correlate drug exposure to anti-inflammatory and anti-sickling effects at different dose levels.
Percentage of sickled cells, time to 50% sickling (t50) and area under sickling curve under hypoxic ex vivo conditions at regular time intervals (days 0, 14, 28, 42 and 66).Percentage change in oxygen affinity (p50) at regular time intervals (days 0, 14, 28, 42 and 66).Change in intracellular reactive oxidative species (ROS) in RBCs at regular time intervals (days 0, 14, 28, 42 and 66). Change in markers of inflammation, adhesion and coagulation activation at regular time intervals (days 0, 14, 28, 42 and 66).
Time frame: days 0, 14, 28, 42 & 66
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