Neurobiological Bases of Paternal Nurturance

Biological Bases of Individual Variation in Paternal Nurturance

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02223429

Enrollment

Registered

2014-08-22

Start date

2014-08-31

Completion date

2016-02-29

Last updated

2017-06-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

Paternal nurturance, Oxytocin, Vasopressin, fMRI, Neurobiology

Brief summary

The overall goal of this project is to identify the genetic, hormonal, and neurobiological influences on paternal nurturing behavior and to determine if fathers' neural responses to infants can be modulated by neuropeptides known to play a role in parenting in experimental animal models. The aim is to determine if pharmacological manipulation of central oxytocin (OT) and vasopressin (AVP) levels influences the neural response to viewing pictures of one's own infant or to hearing cry stimuli. In a double-blind procedure, fathers with 1-3 year old children will be scanned on two separate occasions; once under the influence of OT/AVP and once under the influence of placebo. Fathers will be randomized to either OT or AVP, and order of administration of drug and placebo will counterbalanced across subjects. Fathers will be scanned while viewing pictures of their own and an unknown child and while listening to unknown infant cry stimuli. The investigators hypothesize: * OT will augment the ventral tegmental area (VTA), ventral striatum and medial orbitofrontal cortex (mOFC) response to viewing pictures of one's own child, and will augment the primary auditory cortex (AI) response of fathers to infant cries. * AVP will augment the lateral septum response to viewing own child pictures.

Detailed description

30 fathers of children aged 1-3 will participate in two functional imaging sequence (fMRI) sessions, once under the influence of OT/AVP, and once under the influence of placebo. Fathers will be restricted to men who are living with their biological child and an adult partner (male or female) that they are in a committed relationship with. All fathers will receive two fMRI scans on two different occasions, separated by 2-10 days. 15 fathers will be randomized to intranasal OT, the other 15 will be randomized to intranasal AVP. Within each drug group, the order of administration of drug and placebo will counterbalanced across subjects, such that 15 will receive OT/AVP first, and 15 will receive OT/AVP second. During the fMRI scans, fathers will view pictures of their own and unknown children, as well as unknown adults. Afterwards, while still in the scanner, they will listen to infant cry and control stimuli. After exiting the scanner, fathers will again listen to the cry stimuli and will rate their emotional reaction to the cry stimuli on the following dimensions using a 7 point likert scale: irritated, sympathetic, alarmed, angry, upset, compassionate, distressed, annoyed, and tender.

Interventions

DRUGOxytocin

1 ml solution in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays

DRUGVasopressin

1 ml solution in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays

DRUGPlacebo

1 ml solution in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

* above 18 * biological fathers of 1-3 year old infants who are currently cohabitating with the child's mother * normal or corrected-to-normal vision of 20/40

Exclusion criteria

* current or past history of mental illness * active medical or neurological disorder * current or past history of alcohol or drug dependence * claustrophobic (at the discretion of the PI with subject consultation) * history of seizures or other neurological disorder * history of hypertension, cardiovascular disease, nephritis, diabetes or other endocrine diseases or malignancy * ferrous metal in any part of the body * history of asthma or migraine headaches (can be included at the discretion of the study physician or nurse practitioner if episodes are infrequent and no active problems at time of study, not medicated) * history of head trauma or psychiatric illness, as well as those who are receiving or have received over the past year, medication with known psychoactive effects (included at the discretion of the PI as these are

Design outcomes

Primary

Measure	Time frame	Description
Mean Percent Signal Change in the Anterior Cingulate Cortex	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).
Mean Percent Signal Change in Ventral Tegmental Area (VTA)	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.
Mean Percent Signal Change in Right Ventral Striatum	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.
Mean Percent Signal Change in Right Medial Orbitofrontal Cortex	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.
Mean Percent Signal Change in Caudate Nucleus	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).
Mean Percent Signal Change in the Visual Cortex	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).

Secondary

Measure	Time frame	Description
Change in Plasma Levels of Vasopressin (AVP)	Baseline, Visit 2 (Up to 10 days)	Peripheral levels of AVP will be assessed via assay of plasma collected.
Change in Plasma Levels of Oxytocin (OT)	Baseline, Visit 2 (Up to 10 days)	Peripheral levels of OT will be assessed via assay of plasma collected.
Difference in Cry Rating Scores Between OT and Placebo	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by analyzing the differences between ratings of infant cries under OT and placebo treatment on a 7-point likert scale. Sixteen adjectives will be used to describe two different cries. Participants will rate each cry from 1-7 where one represents not at all and 7 represents extremely. Difference is defined as OT minus placebo scores.
Difference in Cry Rating Scores Between AVP and Placebo	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by analyzing the differences between ratings of infant cries under AVP and placebo treatment on a 7-point likert scale. Sixteen adjectives will be used to describe two different cries. Participants will rate each cry from 1-7 where one represents not at all and 7 represents extremely. Difference is defined as AVP minus placebo scores.
Mean Percent Signal Change in Primary Auditory Cortex	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.
Mean Percent Signal Change in Right Lateral Septum	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between AVP treatment and placebo treatments (AVP-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the AVP group only per protocol.

Countries

United States

Participant flow

Recruitment details

Enrollment took place from 9/29/2014 through 2/3/2016.

Pre-assignment details

Of the 35 participants consented for participation, 32 began the study. Three participants were lost to follow up after signing the consent form.

Participants by arm

Arm	Count
OT First, Followed by Placebo Participants were randomized to receive no more than 1 ml solution of self-administered oxytocin spray in each nostril followed by no more than 1 ml solution of self-administered placebo spray in each nostril. Time between interventions was 2-10 days.	7
Placebo First, Followed by OT Participants were randomized to receive no more than 1 ml solution of self-administered placebo spray in each nostril followed by no more than 1 ml solution of self-administered oxytocin spray in each nostril. Time between interventions was 2-10 days.	8
AVP First, Followed by Placebo Participants were randomized to receive no more than 1 ml solution of self-administered vasopressin spray in each nostril followed by no more than 1 ml solution of self-administered placebo spray in each nostril. Time between interventions was 2-10 days.	8
Placebo First, Followed by AVP Participants were randomized to receive no more than 1 ml solution of self-administered placebo spray in each nostril followed by no more than 1 ml solution of self-administered vasopressin spray in each nostril. Time between interventions was 2-10 days.	8
Total	31

Baseline characteristics

Characteristic	OT First, Followed by Placebo	Placebo First, Followed by OT	AVP First, Followed by Placebo	Placebo First, Followed by AVP	Total
Age, Continuous	33.14 years STANDARD_DEVIATION 4.14	31.88 years STANDARD_DEVIATION 4.61	32.25 years STANDARD_DEVIATION 5.75	34 years STANDARD_DEVIATION 4.75	32.81 years STANDARD_DEVIATION 4.7
Region of Enrollment United States	7 participants	8 participants	8 participants	8 participants	31 participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	7 Participants	8 Participants	8 Participants	8 Participants	31 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 16	0 / 16	0 / 16	0 / 16
other Total, other adverse events	2 / 16	3 / 16	2 / 16	0 / 16
serious Total, serious adverse events	0 / 16	0 / 16	0 / 16	0 / 16

Outcome results

Primary

Mean Percent Signal Change in Caudate Nucleus

The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).