Abstract 4212: A pilot clinical trial to study the effects of Angelica gigas dietary supplement (CognI.Q) on human immune cells (NCT03630328)

Korean Angelica gigas Nakai (AGN)-containing products are marketed as dietary supplements for memory improvement, pain relief and women’s health especially for menopausal symptom management. Decursin (D) and its isomer decursinol angelate (DA) are the major marker compounds in the ethanol extract of AGN root. In rodent models, we and others have shown that D/DA are rapidly converted to decursinol (DOH) after gavage or i.p. injection. Our multi-omic analyses of the TRAMP neuroendocrine carcinomas suggest immune enhancement by AGN. We have published a 20-subject single dose-PK study (NCT02114957) in men and women volunteers in Amarillo, TX (age 21-58 years) with AGN dietary supplement CognI.Q (purchased from Quality of Life Laboratories). For dosage, each person swallowed 4 vegicaps (800 mg AGN) at time 0, the recommended daily dose by manufacturer. The human AUC0-48h for DOH (27579 h.nmol/L) is much higher than for DA (335 h.nmol/L) and D (37 h.nmol/L), supporting extensive conversion from D/DA to DOH (Zhang, J. et al, PLOS One, 2015). Significantly, as secondary endpoint parameters, the neutrophil counts in these human subjects were increased by 71% at 24h post-dose vs. pre-dose. The natural killer cell (NK) mRNA signature in their peripheral blood mononuclear cells (PBMC) was increased by 60~90%. Neutrophils (myeloid lineage) fight against bacterial infection whereas NK cells (lymphoid lineage) not only kill virus-infected cells but also recognize and kill cancer cells, serving as a crucial innate immune surveillance against malignancy in our body. Therefore, we hypothesize that daily intake of AGN dietary supplement (CognI.Q) increases the number and/or activities of neutrophils and NK cells, and in turn may boost human innate immune function against bacterial and viral infections as well as cancer risk. As an initial effort to test our hypothesis, the goal of this pilot clinical trial is to delineate the CognI.Q supplement-specific innate immune enhancement activity in healthy men. We will use a double-blinded, placebo-controlled and crossover trial design so that each man will serve as his own comparison for the immune cell responses to CognI.Q and placebo. Supplement period of 3 weeks will be interspersed with a 2 week washout period. We expect to detect an increase in both neutrophil and NK cell counts compared to placebo. Positive data from our proposed trial will be the first of its kind to support enhancement in healthy US residents of these innate immune cells by an AGN dietary supplement. Detailed study design and interim study analysis will be discussed at the meeting. Citation Format: Deepkamal N. Karelia, Jeremy S. Haley, Todd D. Schell, Diane Hershock, Junjia Zhu, Cheng Jiang, Junxuan Lu, Jinhui Zhang. A pilot clinical trial to study the effects of Angelica gigas dietary supplement (CognI.Q) on human immune cells (NCT03630328) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4212.