Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT01942577 |
| Other study ID # |
Pro00045553 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
N/A
|
| First received |
September 11, 2013 |
| Last updated |
November 2, 2016 |
| Start date |
September 2013 |
| Est. completion date |
September 2016 |
Study information
| Verified date |
December 2015 |
| Source |
Duke University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Institutional Review Board |
| Study type |
Interventional
|
Clinical Trial Summary
The skin and intestinal tracts of humans are covered with microbes, and the gene products of
these microbes are collectively known as the human microbiome. Many studies in recent years
have linked the microbiome to many aspects of human health and disease. Premature infants
are vulnerable to invasive infections, some of which may originate from the microbes that
colonize the skin and in the intestinal tract. Therefore, determining the patterns of early
life colonization and the sources of colonization in these infants may be critical to
determining infectious risks. This prospective study is proposed to identify the sources of
microbes that colonize extremely low birth weight (ELBW; <1000 g birth weight) infants
immediately following birth through the first month of life. The study team plans to
non-invasively survey the skin and stool of ELBW preterm infants in combination with
sampling of their mothers' skin and stool and the intensive care nursery (ICN) environment.
As controls, the study team will perform a similar survey of full term mother-infant pairs.
Samples will be analyzed using high throughput sequencing techniques to determine microbial
content.
Topical barrier sprays or emollients are commonly used early in life in the ELBW infant to
reduce insensible water loss and enhance the integrity of the skin barrier. The effect of
these treatments on the development of the skin microbiome remains unknown. As part of this
study, the study team also proposes the application of two different skin barrier therapies
to small areas on infant's legs to determine the effects of the different treatments on skin
colonization. While all parts of the study are described in this summary and the detailed
description, the remainder of the record focuses on this interventional portion of the study
(Group 2).
The goals of this study are outlined as follows:
1. To elucidate the relationship between microbes in the health care environment and
colonization patterns of the intestinal tracts in preterm and term infants.
2. To understand the relationship between mode of delivery, the health care environment,
and the colonization of the skin in preterm and term infants.
3. To determine the effects of topical skin barrier therapies on the colonization patterns
of the skin in preterm infants.
4. To ascertain the relationship between the composition of the microbes colonizing
preterm and term infants and the development of mucosal and systemic immunity to those
microbes.
Description:
The long term goals of this project are to understand what constitutes protective and
beneficial gut and skin microbial communities and determine approaches to foster and
preserve these communities. By defining the gut and skin-associated microbiological
communities and how these communities are affected by the environment and medical
interventions including barrier therapies, the study team will make essential first-steps
towards achieving these long term goals.
Design & Procedures Study Groups: Potential subjects will be identified among Duke
Hospital-admitted women with expectant preterm (≤30 weeks gestation) or term delivery. A
total of 45 infants will be enrolled into one of three groups.
Preterm microbiome Group 1 (n=10, ELBW preterm infants) will be part of an intensive survey
of infant colonization with bacteria and fungi in addition to the intensive care
environment. This will be a strictly observational group.
Skin microbiome Group 2 (n=30, ELBW preterm infants) will be prospectively evaluated for the
development of the skin microbiome in the context of a topical skin therapy typically used
in the study nursery. Each infant will serve as his/her own control with a
well-circumscribed, small area of the anterior thigh left untreated as the control area.
Full term microbiome Group 3 (n=5, full term infants) will be surveyed for skin and
intestinal colonization and serve as a control group. This will be a strictly observational
group.
Preterm and Full Term One-time Group 4 (n=100 preterm infants born at < 2000 grams and 100
full term). This will strictly be an observational group.
Comprehensive Microbiome Survey of Preterm Infants: Biological and environmental samples
will be collected from enrolled mother and infant subjects (Study Group 1) from the time of
delivery through the first two weeks of life. For stool samples, a minimum of 1 gram will be
collected. For blood samples, 4 ml will be collected. Infant stool samples will be collected
from diapers. Maternal stool and vaginal samples will be collected at the time of caesarian
section using a sterile nylon swab of the distal rectum and vagina. Skin samples will be
collected by gentling rubbing the target area with a sterile nylon swab moistened with
sterile saline. Breast milk samples will be scavenged from left over material after the
feeding of each infant. Since breast milk undergoes a single thaw from frozen storage per
feeding, excess milk may not be stored for subsequent feedings and would be put to waste. A
portion of stool, blood, and breast milk samples will be placed into sterile, nucleic
acid-free tubes. An additional portion of stool, blood, and breast milk samples will be
placed into sterile, nucleic acid-free tubes containing the preservative RNA later. All
stool, breast milk, and blood samples will be frozen at -20°C within 1 hour of collection.
Remaining samples will be placed at 4°C within 18 hr of collection. Samples will be
transferred to -80°C storage within 24 hours of collection. A label carrying a unique sample
number will be placed on each sample as it is collected. A binder with sample labels and a
log of sample numbers, time of collection, sample type key, and special notes regarding
collection, will be placed at the bedside.
It is standard of care for ELBW infants in the Duke Intensive Care Nursery that non-sterile
gloves are worn by all providers and family members for contact with the infant for the
first two weeks of life. Providers and relatives will be asked to place used gloves in a
zip-lock bag at the bedside after contact with the infant. The gloves will be grouped into
zip-lock bags by provider type (medical provider, nurse, or ancillary staff) or relative.
The bags will be collected each shift or day. Glove samples will not be labeled or linked
with individual providers or relatives.
When available, scavenged serum will be used for assessment of antibody specificity in
relationship to colonization patterns of each infant. In some cases, stool samples will be
analyzed for the presence, quantity and specificity of mucosal immunoglobulins. A video
recorder will be positioned above the incubator on a tripod attached to the incubator
vertical rail to capture changes in the infant's environment, including medical or nursing
interventions. The camera will be positioned to capture the infant and the inside incubator
surroundings, while avoiding the faces of those interacting with the infants to preserve
anonymity. When hands or instruments are placed inside the incubator, they will be recorded.
Video will be downloaded onto an external hard drive every 24 hours, and then onto a secure
computer server for analyses. Video recording will be continuous for two weeks except for
the period of time it takes to change the memory card. The video will be coded for the start
and stop times of all clinical care events in order to explore the influence of
environmental changes on the diversity of the infant's microbiome using Mangold Interact
software. Inter-rater reliability will be checked by having video coders score a 30-minute
period of each video, then computing Cohen's kappa.
Microbiome Survey of Full Term Infants: The study team will perform a more limited survey of
five full term infants as a control group (Study Group 3). Samples will be collected from
mothers and infants. Samples will be collected daily while the mother and infant are in the
hospital, which is generally expected to be approximately three days. At hospital discharge,
the parents will be sent home supplies in a prepaid return mailing envelope to be used to
collect skin and stool samples when the infant reaches two weeks of life.
Skin Microbiome Substudy Plan: A controlled study of a commonly used skin treatments (No
Sting protective spray and no treatment) will be performed in 30 ELBW infants (Study Group
2) to determine if No Sting promotes different skin microbial colonization. The current
standard of skin care for ELBW infants in the Duke ICN is application of No Sting to all
external exposed, non-mucosal areas shortly after birth and again at one week of age.
A quarter 1.5 x 3 inch silicon patch with two holes will be applied to each of the infant's
thighs. One hole in each patch will be left untreated (control) while the other is treated
with No Sting. The patches will be used to define the treatment and no treatment areas. The
remainder of the infant's skin will be treated with No Sting therapy at birth and seven days
of life, as per the current standard of care. Daily sampling of each of the sites (No Sting,
and untreated) will be performed by gentle application of a nylon swab for the first two
weeks of life, and then twice weekly until one month of age. Samples will be analyzed for
microbial content. Additional sampling will include infant stool as well as maternal skin,
vaginal, perirectal, and stool samples as outlined in Table 1.
The study team will use non-invasive skin probes to perform daily assessments of
transepidermal water loss (TEWL) and skin pH. TEWL will be measured using the DermaLab® TEWL
probe (Cortex Technology, Hadsund, Dermark), which consists of an open probe with paired
sensors placed at different distances from the skin. Humidity and temperature are measured
in each sensor to calculate vapor pressure gradients. The difference between two vapor
pressure gradient measures is representative of TEWL at that point on the skin [19, 20].
Environmental humidity levels will also be measured using the DermaLab® before obtaining the
TEWL measures. The average humidity readings from the two sensors will be recorded as
environmental humidity. The probe will be thoroughly cleaned with 70% ethanol prior to and
between uses to minimize cross-contamination or microbial transmission. The ethanol will be
allowed to air dry prior to use of the probe. The Extech PH100 meter will be used to measure
skin pH in the range of 0.00 to 14.00. The small flat surface electrode provides a
non-intrusive accurate measure of pH. No Sting will be reapplied on day seven.
Preterm and Full Term One-time Microbiome Survey (Study Group 4): One hundred preterm
infants born at < 2000 grams and 100 full term infants will be included for a one-time data
collection of infant only microbiome samples. For premature infants environmental samples
will also be collected. The same procedures described for Study Group 1 and 2 above will be
used for this single data collection.
