The Biology of Resilience

NCT ID: NCT01011465

Last Updated: 2012-11-26

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

270 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-02-28

Study Completion Date

2012-04-30

Brief Summary

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Positive social relationships have consistently been associated with better health, although the neurobiological underpinnings of these observed effects remain largely unknown. The overall goal of the proposed work is to explore novel biological pathways that may explain how social relationships influence health. Recent theorizing suggests that the oxytocin system may underlie some of the observed beneficial effects. Four hypotheses will be examined:

1. Oxytocin ameliorates the deleterious neuroendocrine, cardiovascular, and subjective effects of stress.
2. Oxytocin and social support have similar and additive stress-buffering effects.
3. Effects of oxytocin are evident among younger and older adults.
4. Effects of oxytocin are stronger in women vs men.

Detailed Description

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Positive social relationships have consistently been associated with better health, although the neurobiological underpinnings of these observed effects are not well understood. Valuable insight may be gained by a life course perspective as it is becoming increasingly apparent that early life social experiences are crucially related to later life functioning and well-being. The overall goal of the proposed work is to explore novel biological pathways that help to explain how social relationships influence health. Recent theorizing on the biology relating positive social and emotional factors to health and patterns of resilience suggest that the oxytocin system may underlie some of the observed beneficial effects. Historically, most work on the oxytocin system in humans has been tied to reproductive outcomes (e.g., lactation), with more limited work on children and young adults. A growing body of experimental research with animals suggests that early in life, oxytocin not only creates powerful social bonds between a mother and child but may also stimulate growth and restorative processes as well as buffer deleterious stress-related neuroendocrine activation throughout the life course. Moreover, the animal literature has suggested that oxytocin is more potent in the presence of higher estrogen levels, leading investigators to hypothesize that effects of oxytocin are stronger in women than men, but few studies have tested this hypothesis in humans. A better understanding of the inter-relationships between oxytocin, social relationships, stress, and health will be gained by examining these factors in a controlled laboratory setting. The immediate goal of this research is to determine whether oxytocin plays a critical role in determining neuroendocrine, cardiovascular, and subjective responses to stress across age and gender, and to examine the effects of oxytocin in relation to those of social support. To achieve these goals, experimental research is proposed to examine the effects of exogenously administered (intranasal) oxytocin on psychological and physiological outcomes, under conditions of stress. The specific aims of this exploratory project are to test the following hypotheses:

1. Oxytocin ameliorates the deleterious neuroendocrine, cardiovascular, and subjective effects of stress.
2. Oxytocin and social support have similar and additive stress-buffering effects.
3. Effects of oxytocin are stronger in women versus men.
4. Effects of oxytocin are similar across a range of younger and older adult ages.

Hypotheses will be tested via a placebo-controlled double blind study using a sample of healthy men and women recruited from the community (overall n = 320). The proposed experimental study will consider oxytocin effects on a range of outcomes. These include autonomic reactivity as measured by blood pressure responses and high frequency heart rate variability (measure of vagal tone). Stress-related cardiovascular phenotypes as characterized by the patterning of ventricle contractility, vascular resistance, and cardiac output will also be assessed. Other outcomes include measures of neuroendocrine effects as measured by levels of cortisol and dehydroepiandrosterone (DHEA) hormone, subjective distress and positive affect. Participants will be randomly assigned to receive either exogenous oxytocin or placebo. They will undergo a social stress manipulation with or without social support (randomly assigned), and outcome measures will be obtained at multiple times during the experimental procedure. The experiment will test whether effects of oxytocin and social support are similar and additive, and will also compare effects of oxytocin and social support across men and women of varying ages. This multidisciplinary study uses a biobehavioral framework to examine interactions between psychological, social, and biological levels of functioning, and is informed by theories of how key early life exposures may impact health over the life course. The provision of an R21 award for this work will facilitate novel research that could have a major impact on our understanding of whether and how oxytocin influences responses to stress in humans. The proposed exploratory research will lay the groundwork for the submission of an R01 grant proposal that will have greater resources for addressing both the questions that cannot be addressed with this more limited mechanism as well as new questions that will undoubtedly arise. Ultimately we expect this project will provide a solid platform from which to launch a larger program of research aimed at identifying how positive social and emotional experiences influence adult health and longevity. A neurobiological understanding of resilience can inform efforts for both prevention and intervention of diseases or problems common in later life.

Conditions

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Oxytocin Placebo

Keywords

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Stress Oxytocin Social Support Resilience

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Oxytocin

One primary experimental manipulation is the receipt of intranasal oxytocin vs placebo spray prior to participation in a psychosocial stress protocol

Group Type EXPERIMENTAL

intranasal oxytocin

Intervention Type DRUG

The aqueous form of oxytocin (oxytocin injection, synthetic) in 10 ml vials is inserted into a spray bottle. The spray bottle is calibrated so that emptying the spray bottle results in delivering 24 IU of oxytocin. No dilution of the original aqueous form of the oxytocin is necessary. 24 IU of oxytocin will be administered at one time only during the procedure. Approximately half the dose will be sprayed into each nostril. Administration will stop after 24 IUs of oxytocin have been administered. Duration of administration is anticipated to be 2-5 minutes

Social support

Intervention Type BEHAVIORAL

Prior to coming to the laboratory, participants are randomly assigned to one of two conditions, requiring them to appear alone or accompanied by a partner. If instructed to bring a same-sex close friend (excluding spouses, participants are joined by their support partners join participants at the start of the stress exposure. The social support condition includes a number of strategies designed to standardize the type of support available to participants across individuals.

No Social Support

Intervention Type BEHAVIORAL

Prior to coming to the laboratory, participants are randomly assigned to one of two conditions, requiring them to appear alone or accompanied by a partner. They are then instructed to bring a same-sex close friend (excluding spouses) with them, or to come alone. If they come to the laboratory without a friend, they engage in all the laboratory procedures without a friend present.

Placebo

The comparison condition for receipt of oxytocin is receipt of a saline intranasal spray

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Participants in the placebo condition receive an equivalent amount of saline for intranasal spray administration. The placebo will be administered at one time only during the procedure. Approximately half the dose will be sprayed into each nostril. Administration will stop after the full amount in the spray bottle has been used. Duration of administration is anticipated to be 2-5 minutes

Social support

Intervention Type BEHAVIORAL

Prior to coming to the laboratory, participants are randomly assigned to one of two conditions, requiring them to appear alone or accompanied by a partner. If instructed to bring a same-sex close friend (excluding spouses, participants are joined by their support partners join participants at the start of the stress exposure. The social support condition includes a number of strategies designed to standardize the type of support available to participants across individuals.

No Social Support

Intervention Type BEHAVIORAL

Prior to coming to the laboratory, participants are randomly assigned to one of two conditions, requiring them to appear alone or accompanied by a partner. They are then instructed to bring a same-sex close friend (excluding spouses) with them, or to come alone. If they come to the laboratory without a friend, they engage in all the laboratory procedures without a friend present.

Social Support

Participants bring a friend to the laboratory who sits with them while they engage in the stress protocol tasks

Group Type EXPERIMENTAL

intranasal oxytocin

Intervention Type DRUG

The aqueous form of oxytocin (oxytocin injection, synthetic) in 10 ml vials is inserted into a spray bottle. The spray bottle is calibrated so that emptying the spray bottle results in delivering 24 IU of oxytocin. No dilution of the original aqueous form of the oxytocin is necessary. 24 IU of oxytocin will be administered at one time only during the procedure. Approximately half the dose will be sprayed into each nostril. Administration will stop after 24 IUs of oxytocin have been administered. Duration of administration is anticipated to be 2-5 minutes

Placebo

Intervention Type DRUG

Participants in the placebo condition receive an equivalent amount of saline for intranasal spray administration. The placebo will be administered at one time only during the procedure. Approximately half the dose will be sprayed into each nostril. Administration will stop after the full amount in the spray bottle has been used. Duration of administration is anticipated to be 2-5 minutes

Social support

Intervention Type BEHAVIORAL

Prior to coming to the laboratory, participants are randomly assigned to one of two conditions, requiring them to appear alone or accompanied by a partner. If instructed to bring a same-sex close friend (excluding spouses, participants are joined by their support partners join participants at the start of the stress exposure. The social support condition includes a number of strategies designed to standardize the type of support available to participants across individuals.

No Social Support

Individuals in this condition do not have a friend present while they are engaging in the laboratory protocol.

Group Type PLACEBO_COMPARATOR

intranasal oxytocin

Intervention Type DRUG

The aqueous form of oxytocin (oxytocin injection, synthetic) in 10 ml vials is inserted into a spray bottle. The spray bottle is calibrated so that emptying the spray bottle results in delivering 24 IU of oxytocin. No dilution of the original aqueous form of the oxytocin is necessary. 24 IU of oxytocin will be administered at one time only during the procedure. Approximately half the dose will be sprayed into each nostril. Administration will stop after 24 IUs of oxytocin have been administered. Duration of administration is anticipated to be 2-5 minutes

Placebo

Intervention Type DRUG

Participants in the placebo condition receive an equivalent amount of saline for intranasal spray administration. The placebo will be administered at one time only during the procedure. Approximately half the dose will be sprayed into each nostril. Administration will stop after the full amount in the spray bottle has been used. Duration of administration is anticipated to be 2-5 minutes

No Social Support

Intervention Type BEHAVIORAL

Prior to coming to the laboratory, participants are randomly assigned to one of two conditions, requiring them to appear alone or accompanied by a partner. They are then instructed to bring a same-sex close friend (excluding spouses) with them, or to come alone. If they come to the laboratory without a friend, they engage in all the laboratory procedures without a friend present.

Female Gender

Effects of oxytocin and social support are examined among women versus men

Group Type OTHER

intranasal oxytocin

Intervention Type DRUG

The aqueous form of oxytocin (oxytocin injection, synthetic) in 10 ml vials is inserted into a spray bottle. The spray bottle is calibrated so that emptying the spray bottle results in delivering 24 IU of oxytocin. No dilution of the original aqueous form of the oxytocin is necessary. 24 IU of oxytocin will be administered at one time only during the procedure. Approximately half the dose will be sprayed into each nostril. Administration will stop after 24 IUs of oxytocin have been administered. Duration of administration is anticipated to be 2-5 minutes

Placebo

Intervention Type DRUG

Participants in the placebo condition receive an equivalent amount of saline for intranasal spray administration. The placebo will be administered at one time only during the procedure. Approximately half the dose will be sprayed into each nostril. Administration will stop after the full amount in the spray bottle has been used. Duration of administration is anticipated to be 2-5 minutes

Social support

Intervention Type BEHAVIORAL

Prior to coming to the laboratory, participants are randomly assigned to one of two conditions, requiring them to appear alone or accompanied by a partner. If instructed to bring a same-sex close friend (excluding spouses, participants are joined by their support partners join participants at the start of the stress exposure. The social support condition includes a number of strategies designed to standardize the type of support available to participants across individuals.

No Social Support

Intervention Type BEHAVIORAL

Prior to coming to the laboratory, participants are randomly assigned to one of two conditions, requiring them to appear alone or accompanied by a partner. They are then instructed to bring a same-sex close friend (excluding spouses) with them, or to come alone. If they come to the laboratory without a friend, they engage in all the laboratory procedures without a friend present.

Male Gender

Consider effects of oxytocin and social support in men versus women

Group Type OTHER

intranasal oxytocin

Intervention Type DRUG

The aqueous form of oxytocin (oxytocin injection, synthetic) in 10 ml vials is inserted into a spray bottle. The spray bottle is calibrated so that emptying the spray bottle results in delivering 24 IU of oxytocin. No dilution of the original aqueous form of the oxytocin is necessary. 24 IU of oxytocin will be administered at one time only during the procedure. Approximately half the dose will be sprayed into each nostril. Administration will stop after 24 IUs of oxytocin have been administered. Duration of administration is anticipated to be 2-5 minutes

Placebo

Intervention Type DRUG

Participants in the placebo condition receive an equivalent amount of saline for intranasal spray administration. The placebo will be administered at one time only during the procedure. Approximately half the dose will be sprayed into each nostril. Administration will stop after the full amount in the spray bottle has been used. Duration of administration is anticipated to be 2-5 minutes

Social support

Intervention Type BEHAVIORAL

Prior to coming to the laboratory, participants are randomly assigned to one of two conditions, requiring them to appear alone or accompanied by a partner. If instructed to bring a same-sex close friend (excluding spouses, participants are joined by their support partners join participants at the start of the stress exposure. The social support condition includes a number of strategies designed to standardize the type of support available to participants across individuals.

No Social Support

Intervention Type BEHAVIORAL

Prior to coming to the laboratory, participants are randomly assigned to one of two conditions, requiring them to appear alone or accompanied by a partner. They are then instructed to bring a same-sex close friend (excluding spouses) with them, or to come alone. If they come to the laboratory without a friend, they engage in all the laboratory procedures without a friend present.

Interventions

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intranasal oxytocin

The aqueous form of oxytocin (oxytocin injection, synthetic) in 10 ml vials is inserted into a spray bottle. The spray bottle is calibrated so that emptying the spray bottle results in delivering 24 IU of oxytocin. No dilution of the original aqueous form of the oxytocin is necessary. 24 IU of oxytocin will be administered at one time only during the procedure. Approximately half the dose will be sprayed into each nostril. Administration will stop after 24 IUs of oxytocin have been administered. Duration of administration is anticipated to be 2-5 minutes

Intervention Type DRUG

Placebo

Participants in the placebo condition receive an equivalent amount of saline for intranasal spray administration. The placebo will be administered at one time only during the procedure. Approximately half the dose will be sprayed into each nostril. Administration will stop after the full amount in the spray bottle has been used. Duration of administration is anticipated to be 2-5 minutes

Intervention Type DRUG

Social support

Prior to coming to the laboratory, participants are randomly assigned to one of two conditions, requiring them to appear alone or accompanied by a partner. If instructed to bring a same-sex close friend (excluding spouses, participants are joined by their support partners join participants at the start of the stress exposure. The social support condition includes a number of strategies designed to standardize the type of support available to participants across individuals.

Intervention Type BEHAVIORAL

No Social Support

Prior to coming to the laboratory, participants are randomly assigned to one of two conditions, requiring them to appear alone or accompanied by a partner. They are then instructed to bring a same-sex close friend (excluding spouses) with them, or to come alone. If they come to the laboratory without a friend, they engage in all the laboratory procedures without a friend present.

Intervention Type BEHAVIORAL

Other Intervention Names

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Pitocin

Eligibility Criteria

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Inclusion Criteria

* age 22-65, BMI \< 30, healthy, English-speaking, 9th grade reading level.

Exclusion Criteria

* any known medical condition (including mental disorders) or on any type of medication
* high levels of social anxiety
* smokers
* high rates of alcohol or drug use
* pregnant or suspected pregnant
* breastfeeding
* blood pressures \> 140/90 mm Hg
* subject does not have a close friend available to participate in the study with him/her
Minimum Eligible Age

22 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Brigham and Women's Hospital

OTHER

Sponsor Role collaborator

Harvard School of Public Health (HSPH)

OTHER

Sponsor Role lead

Responsible Party

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Laura Kubzansky

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Laura D Kubzansky, PhD

Role: PRINCIPAL_INVESTIGATOR

Harvard School of Public Health (HSPH)

Locations

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Harvard School of Public Health

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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Kubzansky LD, Mendes WB, Appleton A, Block J, Adler GK. Protocol for an experimental investigation of the roles of oxytocin and social support in neuroendocrine, cardiovascular, and subjective responses to stress across age and gender. BMC Public Health. 2009 Dec 21;9:481. doi: 10.1186/1471-2458-9-481.

Reference Type BACKGROUND
PMID: 20025778 (View on PubMed)

Kubzansky LD, Mendes WB, Appleton AA, Block J, Adler GK. A heartfelt response: Oxytocin effects on response to social stress in men and women. Biol Psychol. 2012 Apr;90(1):1-9. doi: 10.1016/j.biopsycho.2012.02.010. Epub 2012 Feb 23.

Reference Type RESULT
PMID: 22387929 (View on PubMed)

Other Identifiers

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1R21AG030632-01A2

Identifier Type: NIH

Identifier Source: org_study_id

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