Low-Dose Sublingual Curcumin Improves Red Blood Cell Sickling Kinetics in Sickle Cell Disease: Interim Results from a Pilot Study
Lanetta Bronte, Gershwin Blyden, Patrick Hines, Marta Ferranti, Richard Prince, Joel Friedman, Shavon L Jackson-Michel, Aliya Zaidi, Maria CunninghamAbstract
Background
Vaso-occlusive crisis (VOC) and chronic pain are common complications among individuals with sickle cell disease (SCD). VOC results from endothelial cell integration, hypoxia, inflammation, and accelerated sickling. The study investigates the safety, tolerability, and relative efficacy of VAS-101, a curcumin-based formulation evaluated via sublingual administration, on red blood cell functional biomarkers, anti-inflammatory effects, and patient-reported pain. Objective: To assess the interim clinical, laboratory and patient-reported outcomes (ePRO) from the administration of low-dose VAS-101 in the sublingual cohort.
Methods
The study employs an open-label pilot trial to evaluate the comparative topical and sublingual administration of VAS-101. The sublingual cohort was performed during the April 2025 to September 2025 timeframe. The study population consisted of participants with HbSS. A total of seven participants signed informed consent and were screened, of whom five met eligibility criteria and completed the study. Participants received VASCEPTOR® (VAS-101) administered sublingually at 0.05 mL per application, twice per visit separated by 15 minutes (total 0.1 mL per visit), twice weekly for four weeks (weekly dose 0.2 mL). Clinical and laboratory data - generated for the sublingual cohort - are reported herein. Pain intensity was measured on an electronic 0-10 rating scale. Exploratory psychosocial outcomes were also assessed using the ASCQ-Me Emotional Impact, ASCQ-Me Social Functioning, and PROMIS Fatigue parameters. Functional Fluidics assays included complete blood count (CBC), flow adhesion to P-selectin (FA-WB-Psel) and VCAM-1 (FA-WB-VCAM) compared with the clinically established thresholds for VOC, mechanical fragility indices (MFI), and dynamic sickling assay™ (DSA) kinetics. To detect and monitor systemic inflammation in the recruited subjects, an inflammatory panel was assessed at Rules Based Medicine.
Results
The interim analysis of five sublingual participants demonstrated favorable safety and tolerability. Directional improvements were observed across several patient-reported outcomes. Mean pain scores decreased from 7.0 at baseline to 6.6 by Day 15 (Table 1), with several participants demonstrating clinically meaningful reductions from baseline. Measures of fatigue and energy also improved, with out-of-energy scores decreasing from 3.6 at baseline to 2.2 by Day 22 and fatigue limits improving from 2.8 to 2.0 (Graph a). Psychosocial ePRO measures showed stability or improvement across most participants, including reductions in worry, loneliness, and depressive symptoms. Assessment of red blood cell (RBC) functional biomarkers demonstrated improvements as measured by the DSA. From baseline to Day 29, the Area Under the Curve (AUC10) decreased from 419±140 to 394±118 %*min. Morphological Point of Sickling at 50% (mPoS@50%) increased from 4.9±1.0 to 5.5±1.2 minutes, indicating a delay in sickling. Additionally, the rate of sickling decreased from 47±23 to 38±17 %/min. Collectively, these changes reflect improved sickling kinetics over the treatment period. FA-WB-VCAM and FA-WB-Psel adhesion indices (fAI) were below previously established critical thresholds (FA-WB-VCAM:400 cells/mm2, FA-WB-Psel:50 cells/mm2) predictive of future self-reported vaso-occlusive crises, VOCs in four (4) subjects at baseline and, as expected, no improvements in adhesion were seen at Day 29. Only a single participant exhibited a baseline FA-WB-VCAM fAI exceeding the clinical threshold (>502 cells/mm²). Subsequent analysis of this subject revealed a quantitative reduction to 322 cells/mm² by Day 29. Red blood cell mechanical fragility indices (MFI) were within normal range at baseline and remained stable over the course of the study. Baseline concentrations of standard inflammatory markers were and remained below the lower limit of detection for the initial three participants; consequently, further analytical testing was suspended. .
Conclusions
VAS-101 demonstrated safety and tolerability in the sublingual cohort. Improvements in integrated ePRO and RBC functional biomarkers were noted suggesting potential mechanistic and patient-centered benefits of VAS-101 in individuals with SCD. The resulting biomarkers shift at low dose supports advancement towards dose optimization. Future studies evaluating higher dose and frequency may yield greater improvements in pain, ePRO measures, and laboratory biomarkers. Pre-selecting a cohort that exhibits a higher adhesive burden, indicative of more inflammation may show further improvements in RBC health normalization.