Oxytocin and Brain Responses in Maternal Addiction

NCT02979093 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 201601749
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 2

Brief Summary

A prior study by the principal investigator of this project identified dopamine- and oxytocin-related brain pathways that showed a diminished response when addicted mothers viewed the faces of their own vs. unknown infants, compared with non-addicted mothers. These areas include the hypothalamus, striatum and ventromedial prefrontal cortex. In addition, the investigators plan to examine activation patterns within the salience network, which includes the anterior cingulate cortex and the anterior insula. Oxytocin, a neuropeptide with decreased blood levels seen in addicted mothers, is integrally involved in maternal brain and behavioral responses. When administered intranasally, the pilot data has shown enhanced activation of the striatum, prefrontal cortex (PFC) and amygdala. The purpose of this study is to continue and expand upon the previous investigation of maternal addiction, by conducting a randomized, double-blinded, placebo controlled, crossover study of intranasal oxytocin on maternal brain responses. 150 mothers from the University of Iowa and the Yale Child Study Center will be enrolled (75 with a history of drug addiction and 75 matched control mothers), along with their 2 to 12-month-old infants, to participate in four study visits over a two-month period.

Conditions

Maternal Behavior; Maternal Addiction

Keywords

maternal drug addiction; mother-infant attachment; intranasal oxytocin; unresolved trauma; maternal brain responses; mother-infant synchrony

Outcome Measures

Primary Outcomes (2)

• Effect of Intranasal Oxytocin on Brain fMRI Activation, Independent of Addiction Status (Hypotheses 1 and 2A).

  Brain activation (blood-oxygen level dependent \[BOLD\] signal) in response to reward-related cues (own \[O\] vs. unknown \[U\] infant happy faces). Brain activation (BOLD signal) in response to stress-related cues (own \[O\] vs. unknown \[U\] infant sad faces). Specific regions of interests include the striatum and amygdala (for both happy and sad faces).

  50 minutes after administration of oxytocin or placebo

• Effect of Intranasal Oxytocin on Brain fMRI Activation in Addicted vs Controls Mothers (Hypotheses 1 and 2B)

  Brain activation (BOLD signal) in response to reward-related cues (own \[O\] vs. unknown \[U\] infant happy faces). Specific region of interest includes the ventromedial prefrontal cortex (vmPFC) (interaction effect). Brain activation (BOLD signal) in response to stress-related cues (own vs. unknown infant sad faces). Specific region of interest includes the dorsolateral prefrontal cortex (dlPFC) (interaction effect).

  50 minutes after administration of oxytocin or placebo

Study Arms (2)

Addicted

OTHER

The addiction group will be scanned twice using functional magnetic resonance imaging (fMRI). Subjects will be randomly assigned to receive either the active comparator (intranasal oxytocin spray) or the placebo comparator before the first scanning session. For the second scan (approximately one month later), the subject will receive the other spray which she did not receive at the time of the first scan.

Drug: Oxytocin; Drug: Placebos; Procedure: Functional MRI scanning

Control

OTHER

The control group will be scanned twice using functional magnetic resonance imaging (fMRI). Subjects will be randomly assigned to receive either the active comparator (intranasal oxytocin spray) or the placebo comparator before the first scanning session. For the second scan (approximately one month later), the subject will receive the other spray which she did not receive at the time of the first scan.

Drug: Oxytocin; Drug: Placebos; Procedure: Functional MRI scanning

Interventions

Oxytocin DRUG

All women will receive a nasal spray containing oxytocin.

Also known as: Pitocin, Syntocinon

Addicted; Control

Placebos DRUG

All women will receive a nasal spray containing a placebo solution.

Addicted; Control

Functional MRI scanning PROCEDURE

Study participants undergo two functional MRI scans.

Addicted; Control

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Drug-addicted subjects will be English speaking adult women who:
• are being evaluated for treatment of their addiction or are currently enrolled in treatment programs;
• have an infant \<12 months;
• meet criteria for substance abuse or dependence in the past year, as assessed by MINI International Neuropsychiatric Interview (MINI);
• have a substance abuse history, including use during the most recent pregnancy;
• are recommended at intake for drug-treatment services for substance abuse;
• are 18 years to 40 years old; and
• have been speaking English or enrolled in English-speaking school since age 8.
• Control subjects will be English-speaking adult women who:
• have an infant \<12 months of age;
• do not meet criteria for past or present drug abuse or dependence;
• are 18 years to 40 years old; and
• have been speaking English or enrolled in English-speaking school since age 8.

You may not qualify if:

• Potential drug-addicted subjects will be ineligible if they have:
• severe psychiatric or substance-related symptoms requiring in-patient psychiatric hospitalization or detoxification for suicidality, homicidality, grave disability, physiological alcohol or drug withdrawal within the last 30 days;
• past or present diagnosis of schizophrenia or other psychotic disorders;
• metal implants or other contraindications for MRI scanning;
• pending legal cases (e.g., outstanding arrest warrants or parental rights hearings) prohibiting them from completing the study;
• current pregnancy or plans to become pregnant during the course of the study;
• infants with clinical evidence of in utero drug effects, such as opiate withdrawal symptoms during the neonatal period, facial dysmorphism or intrauterine growth restriction (IUGR) or microcephaly;
• infants with birth weight less than 3 lb. 5 oz.;
• infants who have significant vision, hearing or motor problems (such as cerebral palsy) that cannot be corrected;
• mothers who have significant vision or hearing problems that cannot be corrected;
• out-of-home placement of infant for the past month or more than 50% of child's life;
• delivered more than one baby during most recent pregnancy (twins, triplets, etc.).
• exclusively breastfeeding
• Potential control subjects will be ineligible if they have:
• positive drug toxicology screen at any point in the study;

Sponsors & Collaborators

• Lane Strathearn, MBBS PhD: lead
• Yale University: collaborator

Study Sites (2)

Yale Child Study Center

New Haven, Connecticut, 06520-7900, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Related Publications (8)

• SAMHSA, "Results from the 2011 National Survey on Drug Use and Health: Summary of National Findings" (Substance Abuse and Mental Health Services Administration, Rockville, MD, 2012).

  BACKGROUND

• Chaffin M, Kelleher K, Hollenberg J. Onset of physical abuse and neglect: psychiatric, substance abuse, and social risk factors from prospective community data. Child Abuse Negl. 1996 Mar;20(3):191-203. doi: 10.1016/s0145-2134(95)00144-1.

  PMID: 8734549 BACKGROUND

• Rutherford HJ, Williams SK, Moy S, Mayes LC, Johns JM. Disruption of maternal parenting circuitry by addictive process: rewiring of reward and stress systems. Front Psychiatry. 2011 Jul 6;2:37. doi: 10.3389/fpsyt.2011.00037. eCollection 2011.

  PMID: 21779252 BACKGROUND

• Strathearn L, Li J, Fonagy P, Montague PR. What's in a smile? Maternal brain responses to infant facial cues. Pediatrics. 2008 Jul;122(1):40-51. doi: 10.1542/peds.2007-1566.

  PMID: 18595985 BACKGROUND

• Kim S, Fonagy P, Allen J, Strathearn L. Mothers' unresolved trauma blunts amygdala response to infant distress. Soc Neurosci. 2014;9(4):352-63. doi: 10.1080/17470919.2014.896287. Epub 2014 Mar 17.

  PMID: 24635646 BACKGROUND

• L. C. Mayes, R. Feldman, R. Granger, The effects of polydrug use with and without cocaine on mother infant interaction at 3 and 6 months. Infant behavior & development 20, 489 (1997).

  BACKGROUND

• Strathearn L, Mayes LC. Cocaine addiction in mothers: potential effects on maternal care and infant development. Ann N Y Acad Sci. 2010 Feb;1187:172-83. doi: 10.1111/j.1749-6632.2009.05142.x.

  PMID: 20201853 BACKGROUND

• Strathearn L, Mertens CE, Mayes L, Rutherford H, Rajhans P, Xu G, Potenza MN, Kim S. Pathways Relating the Neurobiology of Attachment to Drug Addiction. Front Psychiatry. 2019 Nov 8;10:737. doi: 10.3389/fpsyt.2019.00737. eCollection 2019.

  PMID: 31780957 BACKGROUND

MeSH Terms

Interventions

Oxytocin

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Lane Strathearn
• Organization: University of Iowa

lane-strathearn@uiowa.edu

3193849464

Study Officials

• Lane Strathearn, MBBS PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

• Linda Mayes, MD

  Yale University

  PRINCIPAL INVESTIGATOR

• Helena Rutherford, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 17, 2016
• First Posted: December 1, 2016
• Study Start: May 5, 2017
• Primary Completion: May 17, 2021
• Study Completion: May 17, 2021
• Last Updated: March 26, 2025
• Results First Posted: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)