Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT04818112 |
Other study ID # |
2009050756 |
Secondary ID |
|
Status |
Active, not recruiting |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
July 12, 2021 |
Est. completion date |
January 31, 2025 |
Study information
Verified date |
May 2024 |
Source |
University of Arizona |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Childhood adversity affects almost two-thirds of the US population, is a major risk factor
for the leading causes of disease and increases US economic health burdens. Childhood
adversity also alters biologic systems, such as the oxytocin hormone, that can affect
attachment behavior. This innovative study has the potential to advance science and improve
mother-infant interaction by testing an early life, home-based, multisensory behavioral
intervention (called ATVV), targeting the oxytocin system, to promote synchronous early
mother-infant interaction, especially critical for mothers who have experienced childhood
adversity.
This two-group randomized clinical trial will test the ATVV's effect on oxytocin system
function and quality of mother-infant interaction. The investigators will enroll 250
first-time healthy mothers carrying a single baby who have a history of childhood adversity,
and obtain baseline data in their third trimester of pregnancy. Soon after birth (before
hospital discharge), mothers (and babies) who continue to be eligible are randomized into the
intervention group and taught to give ATVV daily for 3 months, or randomized into the
Attention Control education group and taught safe infant care. After birth, the investigators
check-in frequently with mothers through weekly phone calls. There are 3 study visits at 1, 2
and 3 months after birth that include survey questions and collection of maternal blood and
infant saliva. Mothers and babies are also video-recorded at 3 months after birth for 4
minutes to assess mother-infant interaction. The investigators follow-up with a phone call at
6 months after birth.
While both groups will benefit from the content and attention the investigators give mothers,
the investigators hypothesize that, compared to the education group, mothers and infants in
the intervention group will have improved oxytocin system function and more synchronous
mother-infant interaction.
Description:
Childhood adversity (e.g., abuse, neglect, or household dysfunction), is a common experience
significantly contributing to the leading causes of death and increased US economic health
burdens. Childhood adversity causes long-term alterations on the nervous, endocrine, and
immune systems well into adulthood, including dampening of the neuropeptide oxytocin (OXT). A
healthy OXT system facilitates responsive social engagement and promotes maternal-infant
(M-I) synchrony (reciprocal gaze, affect speech, and touch). Optimal M-I synchrony fuels
early brain development and prevents low empathy, disruptive behavior, poor social
adaptation, cognitive deficits, and psychopathology in children. The investigators posit that
mothers with childhood adversity will have more difficulty with M-I synchrony, due in part to
a dampened OXT system, and will benefit from interventions that improve responsive,
nurturing, engagement by epigenetic regulation of the OXT system. Most interventions are
costly, complex, and time-consuming. The investigators aim to fill this gap by testing
whether a simple early behavioral intervention (ATVV) will improve OXT system function and
M-I synchrony in mothers with childhood adversity.
The ATVV (Auditory, Tactile, Visual, Vestibular) is a 15-minute behavioral intervention that
is a multisensory infant massage contingent on infant cues. The investigators extend the
known success of ATVV with preterm infants to full-term infants. The investigators will
compare M-I synchrony at 3 postnatal months in 250 first-time mothers (and their full-term
infants) randomized to apply ATVV daily from birth to 3 months (n =125) or receive infant
care education in an attention control group (n = 125). The investigators apply a rigorous
measure of M-I synchrony that micro-codes video-recorded M-I behavior quantifying shared
gaze, affect, speech, and touch. Coding requires only 3-minutes of interaction and is valid
when infants can reliably interact starting by 3 months of age. The investigators will also
assess ATVV's effect on maternal and infant peripheral OXT level, a known biomarker of M-I
synchrony. OXT levels relate to quality of M-I synchrony, yet the investigators extend this
knowledge to identify an epigenetic role of the oxytocin receptor gene (OXTR). The
investigators will analyze maternal plasma for OXTR methylation, OXTR gene expression, OXTR
protein, and oxytocin peptide in pregnancy, and at 1, 2, and 3 postnatal months (along with
infant saliva OXT).
The investigators propose a single-site, randomized, two-group, attention-controlled clinical
trial (N=250 M-I dyads) to test the efficacy of the ATVV multisensory behavioral intervention
to improve OXT system function and M-I synchrony. Adult, nulliparous, English or Spanish
speaking women carrying a single fetus, and scoring 2 or higher on the Adverse Childhood
Experiences scale will be enrolled. The investigators will obtain baseline OXT, demographics
and survey data in the third trimester. Soon after birth (pre-hospital discharge), M-I dyads
who continue to be eligible (e.g., full-term gestation) are randomized into the intervention
group (n = 125) and taught to administer ATVV daily for 3 months or randomized into the
Attention Control group (n = 125) and taught normal safe infant care. There are postnatal
study visits at 1, 2 and 3 months. The investigators follow-up with a phone call at 6
postnatal months (3-months after the intervention period ends) to assess self-report
parenting behavior (a proxy for quality of M-I interaction) that the investigators also
measure at postnatal months 1, 2, and 3.
Aim 1: Evaluate the efficacy of daily ATVV over 3 postnatal months among mothers with
childhood adversity. The investigators hypothesize that compared to the Attention Control
group (n=125), M-I dyads in the ATVV group (n=125) will exhibit:
H1: Higher oxytocin function (i.e., decreased OXTR methylation at candidate sites, and
increased OXTR messenger ribonucleic acid (mRNA), OXTR protein, and OXT in maternal plasma,
and increased OXT in infant saliva) at 1, 2, and 3 postnatal months.
H2: More synchronous eye-to-eye gaze [primary], positive affect [primary], speech, and touch
at 3 postnatal months.
Aim 2: Identify molecular mechanisms in the OXT system underlying M-I synchrony (N=250).
H1: Lower M-I synchrony will be associated with dampening of the OXT system, evidenced by
increased OXTR methylation at candidate sites, and decreased OXTR mRNA, OXTR protein, and OXT
in maternal plasma, and decreased OXT in infant saliva at 3-postnatal months.
Regression based methods (including covariates) will assess ATVV effects on M-I synchrony and
OXT measures, and identify relations among M-I synchrony and oxytocin measures. Clustering
methods will be used to discover molecular profiles. An early behavioral intervention that
successfully promotes M-I synchrony in vulnerable women through epigenetic regulation of the
OXT system can then be tested in a multi-site clinical implementation trial with other
high-risk groups.
Protocol: The Recruiter will introduce the study to potentially eligible pregnant women.
Eligible women who are interested in joining will be consented and scheduled for a 3rd
trimester baseline study visit at the university. The investigators will draw blood for OXT
measures, and collect data in REDCap on demographics, maternal characteristics, and
self-report surveys. Research team members will keep track of when participants have given
birth and meet them in a study site hospital before discharged. The investigators will
collect data on mother and infant health, birth events, and other covariates. At the hospital
visit, women are randomly assigned to either the ATVV group and taught how to administer the
intervention on a daily basis, or are randomly assigned to the Attention Control group and
taught safe infant newborn care.
All participants will receive daily texts to measure daily stress, and intervention
participants also document frequency of the intervention. Using Participatory Guidance to
address women's needs, the investigators will call women each week after birth for a
check-in. In the intervention group, any challenges with the intervention will be discussed
and problem-solved. In the Attention Control group, age-appropriate safe infant care will be
discussed.
After the hospital visit, monthly study visits at 1, 2, and 3 months include collecting
maternal blood and infant saliva, and self-report surveys in REDCap. Women will either
complete REDCap surveys online before each visit, or complete them at the study visit. To
check intervention fidelity, mothers in the ATVV group demonstrate how they perform the
intervention with their infant. The team member instructs mothers how to adapt the ATVV to
their maturing infant and discuss any challenges with the intervention. Mothers in the
Attention Control group are taught age-appropriate safe infant care.
At the 3rd month study visit, the investigators collect behavioral outcome data on M-I
synchrony. All M-I dyads will be video recorded freely interacting with each other for 4
minutes (coding occurs on the last 3 minutes). Video recording occurs when the infant is
alert and ready to interact, > 30 minutes after the end of a breastfeeding or formula
feeding, and data collection order may be adjusted if the baby is sleepy or fussy.
Interactions are micro-coded frame by frame on a computerized system (Noldus, Wageningen, The
Netherlands), consistent with previous research on parent-infant synchrony. Coders, blinded
to group assignment, are trained to 90% inter-rater reliability. Our last interaction with
participants is a phone call at 6-postnatal months to explore duration of the intervention's
effect using the Parenting Stress Index.