The Safety and Intake Rate of a Natural Compound Arctigenin in Healthy Men
Condition: Healthy
Study type: Interventional

Summary: 
      The purpose of this research study is to determine if consuming arctigenin, a natural
      compound from a Chinese herb called Arctium lappa (commonly called greater burdock), is safe,
      and to measure the intake level of arctigenin in blood. Arctigenin is being studied by
      researchers for potential health benefits such as helping to lower the risk of inflammation
      and cancer. A human study has been done measuring the uptake of arctigenin into blood after
      consumption of the herb extract containing arctigenin, and found no toxicity. Studies in mice
      demonstrated that consumption of arctigenin in pure form at a safe level is highly effective
      in inhibition of prostate cancer growth. Therefore, this study is designed to evaluate the
      safety and uptake rate of pure arctigenin in humans, which may be potentially used in the
      future for prostate cancer prevention.
    

Detailed description: 
      Phytochemicals are bioactive natural compounds extracted from plants. Phytochemicals have
      been considered as a major resource for developing non-toxic agents in prevention and
      treatment of chronic diseases, such as diabetes and cancer. However, most phytochemicals have
      low absorption rates, and the dose levels necessary for their beneficial effects can barely
      be achieved in the body after oral consumption, which limits their effect in humans.
      Therefore it is in urgent need to identify phytochemicals of higher uptake rate (or termed
      bioavailability). Arctigenin is a novel anti-inflammatory lignan mainly existing in the seeds
      of the herb Arctium lappa. This herb particularly its seeds has been widely used in
      traditional Chinese medicine to treat inflammation-related diseases such as cold, sore
      throat, and cough. The anti-cancer activity of arctigenin has recently been identified in
      cultured cancer cells and in animal models of several cancers. In prostate cancer, we found
      that arctigenin is highly effective in inhibition of the growth of cultured prostate cancer
      cells, while without affecting normal cells. The strong anti-tumor activity of arctigenin was
      further confirmed in our animal studies with prostate cancer mouse models. By analysis of
      blood concentrations of arctigenin, we found that the effective dose of arctigenin as
      observed in cultured cancer cells was achievable in mouse blood after consumption of
      arctigenin at a safe level, which suggests that the bioavailability of arctigenin is
      adequately high for its anti-cancer effect in organisms. We therefore propose a phase I
      one-arm dose escalation study to confirm the safety and bioavailability of arctigenin in
      healthy men, and to determine the dosage for future phase II studies in prostate cancer
      prevention. The study will use the traditional 3+3 design, which is the most widely used
      phase I design in oncology. Three dose levels of arctigenin will be tested, and participants
      will receive two capsules of arctigenin per day for 28 days, each capsule containing 250 mg
      of arctigenin. Initially there will be three participants on each dose level. If there is no
      dose-limiting toxicity (DLT) observed in any participant, the dose will be escalated to the
      next level. If DLT is observed in one or two participants, three more participants will be
      added. If DLT is observed in one or two participants out of the six, the dose will be
      escalated to the next level. If DLT is observed in three or more participants of the six, the
      previous dose level will be considered as the maximally tolerated dose (MTD), and three more
      patients will be added to the MTD group for a more accurate evaluation of the safety. The
      estimated MTD is the highest dose level with observed toxicity rate less than 0.33. Blood
      samples will be collected at baseline, during week 2 and on the last day of the study. Urine
      samples will be collected once a week during the intervention. On the last day of the
      intervention (Day 28) we will perform a single dose challenge with arctigenin and collect
      blood at baseline and at 1h, 2h, and 3h after arctigenin consumption in the morning.
      Arctigenin and its glucuronide will be analyzed in blood and urine using high performance
      liquid chromatography (HPLC)
    

Intervention name(s): Arctigenin
Intervention type(s): Dietary Supplement
Intervention description(s): Arctigenin capsule
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Other