Cyclic Variation in Micronutrient Concentrations and Plasma Volume
Condition: Plasma Volume; Micronutrients; Menstrual Cycle
Study type: Observational

Summary: 
      The overall goal of this study is to examine the influence of the menstrual cycle on
      micronutrient concentrations and plasma volume in healthy, reproductive-age women with
      regular cycles. The investigators aim to quantify changes in micronutrient biomarker
      concentrations (zinc, copper, iron, and vitamin A) and plasma volume across the menstrual
      cycle in healthy women.
    

Detailed description: 
      This is a longitudinal prospective study wherein all subjects will be examined at three time
      points within a single menstrual cycle: the early follicular phase (~day 2), periovulation
      (~day 12), and the luteal phase (~day 21)-based on an approximate 28-day cycle length. The
      actual days of visits will be adjusted for the length of the woman's menstrual cycle. At
      least 35 non-pregnant women ages 18 to 44 years will be recruited as a convenience sample of
      eligible women in the State College area and surrounding towns within Centre County,
      Pennsylvania, USA. If a woman responds to the recruitment, she will be asked a set of
      pre-screening questions to determine eligibility. If a woman is thought to be eligible, she
      will complete a verbal consent for the screening (and the actual screening will occur at the
      first visit). Then she will be invited to the Clinical Research Center (CRC), a service unit
      in Penn State's Clinical and Translational Science Institute, for full screening and
      participation. Before scheduling the visit, the woman will be asked for the expected date of
      the first day of her next menstrual period. The woman will then be tentatively scheduled for
      her first visit at the CRC approximately 1 day after this date (avoiding weekend days).

      As part of the preparation for study visits, the woman will be asked to fast the night before
      her visit. Women will also be asked to avoid alcohol intake for 12 hours preceding their
      scheduled visits to the CRC, and to drink plenty of water. On the morning of the visit, the
      woman will arrive at the CRC, go through complete screening (including height, weight, blood
      pressure, and pregnancy test). If eligible for the main study, the woman will then go through
      the consent process for the main study. If the woman gives consent to participate, the
      investigators will then proceed with study measurements (including a questionnaire and body
      composition measurement).

      Following these measurements, the study nurse or doctor will insert an IV into the vein of
      one arm and an initial baseline blood draw will be taken (~15-20 ml, in several tubes). This
      blood will be used for biomarker assessment (hemoglobin, hematocrit, vitamins, minerals, etc)
      and as a blank sample before the dye injection. Next, indocyanine green (ICG) will be used to
      measure plasma volume. A solution will be prepared using 25 mg of ICG lyophilized powder
      dissolved in 10 ml of sterile water. The investigators will draw enough solution to inject
      0.25 mg/kg body weight into a syringe. The syringe will be weighed to measure the exact
      amount. Then the solution will be injected via the IV and flushed with saline. After 2
      minutes, five ~3 ml blood samples will be drawn at intervals of 45 seconds over the next 3
      minutes. Expected total volume of blood drawn at the visit will be <35 mL.

      At the end of this first visit the participant will be given a home-based fertility monitor
      to take home to track her cycle. She will be instructed on how to use the monitor at home but
      the research team will maintain contact with her on a regular basis to ensure that she is
      using the monitor correctly. She will conduct a daily urine test with the monitor, which uses
      urine hormone concentrations to track the stage of the menstrual cycle for the participants
      by displaying low, high, or peak fertility. The second and third visits will be scheduled
      using an algorithm that takes into consideration the woman's menstrual cycle length and
      results from a home-based urine fertility monitor.

      At the third visit, the participant will return the monitor to the CRC and the urine test
      results, which are stored in the monitor, will be retrieved. At the end of the third visit
      her study participation is complete but the investigators will keep in contact with her to
      record the first date of her next cycle (to calculate actual cycle length).
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Eligible women in the State College area and surrounding towns within Centre County,
        Pennsylvania, United States.
      
Biospecimen description: 
      Plasma, serum and urine samples
    
Keywords: Plasma volume, micronutrient, estrogen, progesterone