Output details

Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: Safety, pharmacokinetics and effect on the insulin-like growth factor axis.

The author made a substantial contribution to the conception and design of the study, to the organisation of the conduct of the

study and to analysis and interpretation of study data. The author helped to draft the output and critique the output for important

intellectual content.

Steward conceived, designed the trial and obtained funding from National Cancer Institute (USA). Steward wrote the protocol and supervised the trial, liaising with collaborating US site. Supervised clinical research fellow and reviewed data throughout. Steward managed regulatory affairs

and critiqued the publication during its development. Brown directed and managed all pharmacokinetic and pharmacodynamics laboratory analyses on clinical samples; novel assay development and validation, data manipulation and interpretation. Brown was joint supervisor of the clinical research fellow and supervisor of the PhD student driving the laboratory component of the project. Brown helped to draft and critiqued the publication during its development.

Steward, clinical academic, led all aspects of trial (unique challenges as involved dietary agents and academic led with no industry sponsorship) over ~5 years. Designed phase I/II trial, wrote protocol, arranged regulatory/ethics approval, obtaining IMP, ran trial and recruited 40 volunteers, liaised with US co-investigators, collected/analysed clinical. Karen Brown directed the associated laboratory component, involving assay validation and comprehensive HPLC-UV and LC-MS/MS analysis of plasma for pharmacokinetic and metabolite profiling (~300 samples plus controls), chemical synthesis of metabolite standards, immunoassay of pharmacodynamic biomarkers (IGF-1, IGFBP-3, M1dG and PGE2) in pre/post dose plasma (~320 samples) and all associated data analysis.