Double-blinded chemoprevention trial: berry gel shows efficacy relative to placebo

Previous studies from our labs showed that topical application of a bioadhesive gel containing 10% w/w freeze dried black raspberries (BRB gel; applied 0.5 gm q.i.d.x 6wk) to lesions of oral epithelial dysplasia (OED) elicited positive effects including histologic and clinical regression, reduction in loss of heterozygosity (LOH) indices and COX-2 reduction.  These pilot studies, however, did not include a placebo gel (Pgel).

Objective: We are currently conducting a longer duration (3 months) double-blinded, placebo-controlled, multicenter chemoprevention trial that includes the previous evaluative parameters plus tissue metabolic profiling, and p16 methylation analyses.

Method: Twelve patients have completed the 3 month clinical trial to date (n=8 active, n=4 placebo). Evaluated parameters include: 1) clinical lesional area [normalized image size pixels to internal scale (ruler in photo)], 2) histopathology (2 board-certified oral pathologists).  All evaluations were conducted by an investigator(s) who was/were blinded to the patients’ gel group.

Result: BRB gel significantly reduced lesional size in 6 of 7 evaluable lesions (9.7% to 100%), with complete regression observed in 2 lesions (p=0.03, two-tailed, Wilcoxon signed-rank test). Conversely, Pgel treated lesions increased in area (n=4, increases ranged from 6.6% to 81.8%). Histologic comparisons of pre versus post tissues showed a significant post-treatment reduction in histologic grades in the BRB gel treated lesions (p=0.03, two-tailed, Wilcoxon signed-rank test); whereas no significant differences were detected in the Pgel treated tissues’ histopathology. Comparisons of post-treatment lesional areas of BRB gel relative to Pgel showed a significant difference (n=7 BRB gel, n=4 Pgel, p=0.02, two-tailed, Mann Whitney U).  Studies to assess effects on LOH indices, p16 methylation and metabolic profiling are ongoing.

Conclusion: These preliminary data validate the essential contribution of BRB constituents in OED chemoprevention and support our pilot trial data.

Supported by T32DE14320, R01CA129609, RC2CA148099, R21CA135478.