Bisphenol A Controlled Exposure Study
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - Bisphenol A (BPA) is a chemical that is used primarily to make plastics, resins, and
      thermal paper. Most people are exposed daily to low levels of BPA that leaches into food and
      water from plastic products, including water and baby bottles. However, not all of the risks
      of BPA are known. Researchers want to learn more about how BPA acts in the body, and how the
      body gets rid of BPA.

      Objectives:

      - To study controlled exposure to BPA and its effects on the body.

      Eligibility:

      - Healthy, non-obese volunteers between 25 and 45 years of age.

      Design:

        -  Participants will have six visits over about 2 to 4 weeks for this study.

        -  At the first visit, participants will be screened with a physical exam and blood and
           urine tests. They will complete a questionnaire about exposure to BPA-containing
           products. They will also receive a list of medications that should not be taken during
           the study period.

        -  The second visit will last about 13 hours. Participants will fast for 8 hours before the
           visit. They will then have a single dose of d-BPA (a modified form of BPA that is easier
           to study in the body). Regular blood samples will be taken over the 13-hour visit. All
           urine will also be collected. Participants will receive breakfast and lunch during the
           visit.

        -  Participants will have four follow-up visits. They will collect and store all of their
           urine between each follow-up visit. Blood samples will be collected at the follow-up
           visits....
    

Detailed description: 
      Bisphenol A (BPA) is utilized primarily in the manufacture of polycarbonate plastic and epoxy
      resins, which are widely used in the fabrication of baby bottles and food can linings.
      Consequently, human exposures to BPA are widespread. However, there is still uncertainty
      about the extent and nature of these exposures. This pharmacokinetic (PK) study is aimed at
      refining our understanding of the metabolism and excretion of BPA following two different
      routes of administration. This investigation is also intended to help resolve current
      controversies in BPA risk assessment. We will administer 100 microgram/kg body weight (bw) of
      deuterated BPA (d-BPA) orally and/or dermally (as an ethanol solution or a
      carboxymethylcellulose suspension), in up to 50 participants, with comparable numbers of men
      to women, and collect blood and urine for measurements of d-BPA and d-BPA conjugates at
      selected time points over a six day period post-dosing. The use of d-BPA will allow the
      detection of the administered BPA to be distinguished from background BPA. The primary
      endpoint of the study is detection of measurable d-BPA and d-BPA conjugates in blood and
      urine after administration of a single dose of 100 microgram/kg bw d-BPA applied orally
      and/or dermally (as an ethanol solution or a carboxymethylcellulose suspension). Participants
      will be given an option to complete either one or both phases of the study, the exposure
      visits separated by a period of at least 4 weeks. Dose selection was based on balancing the
      need for detectable levels of BPA in blood and urine to meet the objective and the need to
      minimize human subject risk. Data from the first 3 participants in the study, who received
      oral d-BPA, confirmed dosing during the oral pilot phase was sufficient in capturing
      measurable d-BPA in blood and urine and will continue at 100 microgram/kg bw of d-BPA for
      oral dosing. Dermal exposure will consist of a pilot phase for this route of administration
      comprising 4 participants to assess whether 100 microgram/kg bw of d-BPA applied to the skin
      is sufficient to obtain measurable d-BPA in blood and/or urine in order to establish PK
      parameters and to evaluate whether the time points are appropriate and necessary. If needed,
      the dermal pilot phase will be repeated using an ethanol solution rather than a
      carboxymethylcellulose suspension. The design includes sufficient sampling of blood and urine
      to define relevant PK parameters, including the rate of BPA absorption, plasma elimination
      rate, area under the curve (AUC) and apparent clearance, half-life, the urinary excretion
      rate, and the fractional metabolic clearance of the glucuronide and sulfate conjugates.
    

Intervention name(s): deuterated-Bisphenol A (d-BPA)
Intervention type(s): Other
Intervention description(s): The primary endpoints are key pharmacokinetic measurements of d-BPA and d-BPA conjugates in blood and urine over 6 days after a single dose of oral and/or ethanol solution dermal application and/or a carboxymethylcellulose suspension dermal application of a dose of 100 micro g/kg bw of d-BPA.
Intervention MeSH terms: Bisphenol A
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Biologic Sample Collection; Metabolism; Healthy Volunteer; HV