Recombinant Human Prolactin for Lactation Induction

The study is a randomized, double blind, placebo controlled trial. Subjects will be admitted
to the General Clinical Research Center (GCRC) as outpatients to undergo their baseline
pumping study. One lactation consultant will educate all subjects in the proper technique for
pumping on the first day of the study and will evaluate their technique on day 5 and day 8 of
the study. The lactation consultant will also instruct patients to record the volume of milk
pumped and the time of each pumping episode. Subjects will be encouraged to have direct
contact with their infants prior to pumping. All infant contact, infant latching onto the
breast and mother's stress level will also be recorded throughout the study. Starting at 8 am
on day 1, a hospital grade breast pump will be used to drain both breasts as confirmed by the
absence of milk flow for 2 min during each episode of pumping and by palpation. Pumping will
be performed in this manner every 3 hours around the clock. Subjects will be allowed a 5 hour
window to sleep, however, as long as the total number of pumping episodes equals 8 in 24
hours.

During the first episode of pumping, a baseline prolactin level will be drawn immediately
before the start of a pumping and repeated at 10 min intervals for 60 min, and then every 30
min for a total of 3 hours to document the peak prolactin level. An intravenous line will be
placed to draw blood. Subsequently, subjects will be randomized to receive prolactin or
placebo. On the morning of days 2, 5 and 8, blood will be collected for a prolactin level
before medication injection. Subsequently, prolactin 60 mg/kg or placebo will be injected
subcutaneously by the study nurse 3 hrs after the last pumping episode. On days 2 and 8,
additional blood will be collected every 10 min for the first hour, every 30 min for hour 2
and 3, then at 4, 6 and 8 hours after injection to determine the peak prolactin level during
a pumping session. Subjects will then drain both breasts as confirmed by the absence of milk
flow for 2 min during each episode of pumping and by palpation and milk volume recorded. The
subjects' vital signs will be monitored immediately before and every 15 minutes for 1 hr,
every 30 min for hours 2 and 3, and then at 4, 6 and 8 hours after injection of
prolactin/placebo. Temperature will be measured before the injection, every hour for hours 2
and 3, and then at 4, 6 and 8 hours after injection of placebo/prolactin. If there are no
changes in vital signs, on days 5 and 8 vital signs will be monitored at baseline, only.
Subjects will be taught to do SC injections on their own and will administer their second
dose of SC r-hPRL or placebo 12 hours after the first dose. Subjects will continue every 12
hour SC r-hPRL or placebo administration for the next 7 days. Subjects will be asked to
refrigerate all milk and bring it in to GCRC visits so that the volume that is recorded can
be confirmed and for testing the milk composition and prolactin level before it is given to
the infants. The final prolactin injection will be given on the evening of study day 8. All
side effects in the mother and baby will be recorded daily throughout the study. Subjects
will return for a final outpatient visit on day 16, to determine if any treatment effect
persists. During this visit, milk will be pumped at baseline and volume recorded. In
addition, blood will be drawn at 10 min intervals for 60 min, and then every 30 min for a
total of 3 hours to document the peak prolactin level. Subjects will turn in their pumping
diary the next day.

Inclusion Criteria:

- Healthy women, aged 18-45 years

- Lactation insufficiency postpartum

- Subjects will be women with children in the neonatal Intensive Care Unit (ICU) who are
pumping breast milk for their infant's nutritional support and to maintain their milk
supply.

- Subjects will have given birth at a gestational age of at least 24 weeks, and will
generally be recruited 4-8 weeks postpartum.

Exclusion Criteria:

- Medications known to increase prolactin

- Anatomical breast abnormalities

- Use of medication contraindicated in breastfeeding mothers

- Allergies to mannitol

- Current use of hormonal contraception

- Previous mammoplasty or breast augmentation, unless they have successfully nursed an
infant for 3 months in the past without requiring supplemental formula.