Lactation
Conditions
Keywords
Lactation, Breastfeeding, Premature infants, Prolactin, Primary lactation insufficiency
Brief summary
The purpose of the study is to assess the safety and determine the effects of the hormone prolactin on lactation (breast milk production).
Detailed description
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.
Interventions
60 mcg/kg every 12 hours
BIOLOGICALRecombinant human prolactin
60 mcg/kg given every 12 hours or every 24 hours
BIOLOGICALNormal Saline
twice per day
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Breast Milk Volume Baseline to 7 Days | 7 days |
Secondary
| Measure | Time frame |
|---|---|
| Breast Milk Prolactin Levels | 7 days |
Countries
United States
Participant flow
Recruitment details
2004-2008 Academic Hospital, clinical research center
Participants by arm
| Arm | Count |
|---|---|
| Placebo Twice Per Day Placebo group
Normal Saline : twice per day | 4 |
| Recombinant Human Prolactin Twice Per Day Recombinant human prolactin every 12 hours
Recombinant Human Prolactin : 60 mcg/kg every 12 hours | 3 |
| Recombinant Human Prolactin Once Per Day Recombinant human prolactin alternating with placebo every 12 hours
Recombinant human prolactin : 60 mcg/kg given every 12 hours or every 24 hours | 3 |
| Total | 10 |
Baseline characteristics
| Characteristic | Recombinant Human Prolactin Twice Per Day | Recombinant Human Prolactin Once Per Day | Placebo Twice Per Day | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 4 Participants | 10 Participants |
| Age, Continuous | 30 years STANDARD_DEVIATION 5 | 32 years STANDARD_DEVIATION 6 | 30 years STANDARD_DEVIATION 5 | 32 years STANDARD_DEVIATION 5 |
| Region of Enrollment United States | 3 participants | 3 participants | 4 participants | 10 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 4 | 1 / 4 | 2 / 3 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 3 |
Outcome results
Primary
Change in Breast Milk Volume Baseline to 7 Days
Time frame: 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Twice Per Day | Change in Breast Milk Volume Baseline to 7 Days | -12 % change from baseline | Standard Error 27 |
| Recombinant Human Prolactin Twice Per Day | Change in Breast Milk Volume Baseline to 7 Days | 429 % change from baseline | Standard Error 338 |
| Recombinant Human Prolactin Alternating With Placebo | Change in Breast Milk Volume Baseline to 7 Days | 44 % change from baseline | Standard Error 28 |
Secondary
Breast Milk Prolactin Levels
Time frame: 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Twice Per Day | Breast Milk Prolactin Levels | 60 mcg/L | Standard Error 13 |
| Recombinant Human Prolactin Twice Per Day | Breast Milk Prolactin Levels | 118 mcg/L | Standard Error 25 |
| Recombinant Human Prolactin Alternating With Placebo | Breast Milk Prolactin Levels | 118 mcg/L | Standard Error 25 |