Relative Bioavailability of Two Different Milk Thistle Formulations
Condition: Healthy
Study type: Interventional

Summary: 
      This is a single dose, randomized, cross-over pharmacokinetic study in healthy volunteers
      (n=12) of two dietary supplement formulations. The Product B® IsaGenesis® formulation
      represents a newer reformulation of an existing product known simply as IsaGenesis®. Beyond
      some changes in the relative abundance of some of the constituents of the earlier IsaGenesis®
      formulation, the Product B® IsaGenesis® product has been formulated as a liquid-gel
      formulation (rather than a dried powder extract) which is theorized to enhance the absorption
      and bioavailability of the contained botanical constituents. The purpose of this study is to
      compare the two dietary supplement formulations relative to the absorption of two compounds
      contained within the supplement known as the flavonolignans silybin A and silybin B into the
      bloodstream after oral administration of capsules.
    

Detailed description: 
      The study involves a total of five (5) visits to the University of Florida Shands CRC located
      in the Clinical Translational Research Building in Gainesville, and is expected to last
      approximately 6 weeks.

      Screening / Informed Consent:

      The Screening Visit will be conducted in the CRC and is expected to last approximately 1
      hour.

      After obtaining written Informed Consent, study subjects will be interviewed about their
      medical history and the protocol's Inclusion/Exclusion criteria will be discussed. All
      potential participants must be nonsmokers, not taking prescription or over-the-counter
      medications or botanical/nutritional supplements (inclusive of vitamins). Additionally,
      participants are requested to abstain from alcohol use 24 hours prior to the study health
      screen lab work or any scheduled study visit should they participate fully in the study.

      During this initial visit, interested subjects will have blood samples drawn for health
      screening purposes including baseline serum chemistries, complete blood count, urinalysis,
      and a urine pregnancy test (women) which will precede a subsequently scheduled physical exam
      and possible study participation. Copies of the laboratory results will be made available to
      study subjects at their request. Lastly, a 12-lead electrocardiogram will be obtained.

      Study Visits The following section describes the study procedures for the two major study
      visits at the CRC following Informed Consent and a satisfactory medical screening.

      Following an overnight fast (abstention from eating any food items after 9 pm in the evening
      prior to the scheduled visit), subjects will arrive at the CRC the morning of the active
      Study Days where they will remain for approximately 8 hours on each day. After checking in,
      and under medical supervision, skilled CRC staff will place an indwelling venous catheter in
      each subject's arm to facilitate serial blood sampling. Female subjects will provide a urine
      sample for a pregnancy test. At approximately 8:00 AM subjects will be administered 2
      capsules of either Product B® IsaGenesis® (2 capsules; 1280 mg per capsule) or IsaGenesis® (2
      capsules; 1070 mg per capsule) depending on the randomization sequence assigned by the
      Investigational Pharmacy Services. Capsules will be administered with 240 ml of room
      temperature water which the subjects will be asked to drink in its entirety. Subjects will
      remain in a fasted state for 4 additional hours following administration of either
      formulation to eliminate any potential effect of food on absorption. Standard meals will be
      served to all subjects at least 4 hours post-dosing. The composition and amount of food eaten
      throughout the day will be recorded.

      Blood sample collection and processing will be done by an indwelling venous catheter to
      facilitate serial blood sampling, a total of 9 blood samples (~10 ml each) will be taken over
      an 8-hour period during each of the two primary study days. Specific time points of blood
      collection will be immediately prior to the dose (0 time point), of either Product B®
      IsaGenesis® (2 capsules; 1280 mg per capsule) or IsaGenesis® (2 capsules; 1070 mg per
      capsule) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours.

      This single dose assessment of the Product B® IsaGenesis® (2 capsules; 1280 mg per capsule)
      or IsaGenesis® (2 capsules; 1070 mg per capsule) pharmacokinetics will be conducted with each
      of the two described formulations as a single dose assessment in a randomized crossover
      fashion. Following the completion of the initially product administration and sample
      collection, a minimum 7-day wash-out period will occur prior to scheduling each subject's
      return for the assessment of the alternate product (under identical study conditions and
      collection times).

      Study Exit Visit The investigators will have the subjects return within 7 days of completing
      the second study formulation pharmacokinetics assessment to have "exit" follow-up lab work
      consisting of a basic serum chemistry panel and CBC as well as urinalysis.
    

Intervention name(s): Product B® IsaGenesis®; IsaGenesis®
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): This will be a crossover comparison of a one time dose of the liquid-gel formulation contained in 2 capsules; 1280 mg/capsule.; This will be a crossover comparison of a one time dose of the dried powder extract contained in 2 capsules; 1070 mg /capsule.
Other intervention name(s): milk thistle extract; milk thistle extract
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: dietary supplement; pharmacokinetics; Healthy Volunteers