Study of the Effects of Oxytocin on Attentional Bias and Startle in PTSD

NCT03211013 | Completed Early Phase 1 FDA Drug

• 1 other identifier: WOS0022ADM
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will test whether intranasal oxytocin (24 IU vs placebo) will induce effects on attention bias and startle comparable to those the investigators have shown to be induced by the presence (vs absence) of a service dog in Veterans diagnosed with PTSD. This possibility is suggested by a 2015 study showing that urinary oxytocin levels are elevated in association with mutual gaze between dogs and their owners.

Conditions

Posttraumatic Stress Disorder

Keywords

oxytocin; PTSD; attention bias; startle

Outcome Measures

Primary Outcomes (2)

• Change in attentional bias

  Changes between oxytocin vs. placebo lab sessions in the asymmetric allocation of visual attention to one or another of a pair of visual stimuli presented simultaneously as quantified by gaze tracking

  1-2 weeks

• Change in startle response -heart rate

  Difference between oxytocin vs. placebo lab sessions in the magnitude of pre-to-post startle stimulus change in heart rate

  1-2 weeks

Other Outcomes (2)

• Change in startle response -EDA

  1-2 weeks

• Change in startle response -EMG

  1-2 weeks

Study Arms (2)

Immediate Oxytocin

EXPERIMENTAL

Participants randomly assigned to this arm will receive OT nasal spray (24 IU) at laboratory visit 1 and placebo nasal spray at visit 2. The order will be masked for participants and study staff.

Drug: Oxytocin; Drug: Placebos

Delayed Oxytocin

PLACEBO COMPARATOR

Participants randomly assigned to this arm will receive placebo nasal spray at laboratory visit 1 and OT nasal spray (24 IU) at visit 2. The order will be masked for participants and study staff.

Drug: Oxytocin; Drug: Placebos

Interventions

Oxytocin DRUG

single-dose administration of OT nasal spray, complete computer-based tasks post-dose for approximately 1 hour

Also known as: syntocinon

Delayed Oxytocin; Immediate Oxytocin

Placebos DRUG

single-dose administration of placebo nasal spray, complete computer-based tasks post-dose for approximately 1 hour

Delayed Oxytocin; Immediate Oxytocin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Because data obtained by the investigators were exclusively from male combat veterans, and because the inclusion of female veterans presents challenges related to both variable interaction with gonadal hormones over the menstrual cycle and the need to test for pregnancy, only males will be enrolled into this protocol.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• US military Veteran
• Current posttraumatic stress disorder
• Medically healthy

You may not qualify if:

• DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder
• Active drug or alcohol use disorder within past 90 days
• Currently participating in a clinical drug trial
• Regular nasal obstruction or nosebleeds (use of saline or nasal decongestant permitted if subject has transient cold only)
• Active medical problems: unstable seizures, significant physical illness (e.g., serious liver, renal, or cardiac pathology)
• Sensitivity to preservatives, in particular E 216, E 218, and chlorobutanol hemihydrate
• Significant hearing or vision impairments
• Habitually drinks large volumes of water

Sponsors & Collaborators

• Palo Alto Veterans Institute for Research: lead

Study Sites (1)

VA Palo Alto Health Care System

Menlo Park, California, 94025, United States

Location

Related Publications (22)

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  PMID: 25883356 BACKGROUND

• Ayers LW, Missig G, Schulkin J, Rosen JB. Oxytocin reduces background anxiety in a fear-potentiated startle paradigm: peripheral vs central administration. Neuropsychopharmacology. 2011 Nov;36(12):2488-97. doi: 10.1038/npp.2011.138. Epub 2011 Jul 27.

  PMID: 21796104 BACKGROUND

• Baumgartner T, Heinrichs M, Vonlanthen A, Fischbacher U, Fehr E. Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron. 2008 May 22;58(4):639-50. doi: 10.1016/j.neuron.2008.04.009.

  PMID: 18498743 BACKGROUND

• Beery AK, Zucker I. Oxytocin and same-sex social behavior in female meadow voles. Neuroscience. 2010 Aug 25;169(2):665-73. doi: 10.1016/j.neuroscience.2010.05.023. Epub 2010 May 16.

  PMID: 20580660 BACKGROUND

• Benjet C, Bromet E, Karam EG, Kessler RC, McLaughlin KA, Ruscio AM, Shahly V, Stein DJ, Petukhova M, Hill E, Alonso J, Atwoli L, Bunting B, Bruffaerts R, Caldas-de-Almeida JM, de Girolamo G, Florescu S, Gureje O, Huang Y, Lepine JP, Kawakami N, Kovess-Masfety V, Medina-Mora ME, Navarro-Mateu F, Piazza M, Posada-Villa J, Scott KM, Shalev A, Slade T, ten Have M, Torres Y, Viana MC, Zarkov Z, Koenen KC. The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium. Psychol Med. 2016 Jan;46(2):327-43. doi: 10.1017/S0033291715001981. Epub 2015 Oct 29.

  PMID: 26511595 BACKGROUND

• Ditzen B, Schaer M, Gabriel B, Bodenmann G, Ehlert U, Heinrichs M. Intranasal oxytocin increases positive communication and reduces cortisol levels during couple conflict. Biol Psychiatry. 2009 May 1;65(9):728-31. doi: 10.1016/j.biopsych.2008.10.011. Epub 2008 Nov 22.

  PMID: 19027101 BACKGROUND

• Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC. Oxytocin improves "mind-reading" in humans. Biol Psychiatry. 2007 Mar 15;61(6):731-3. doi: 10.1016/j.biopsych.2006.07.015. Epub 2006 Nov 29.

  PMID: 17137561 BACKGROUND

• Ellenbogen MA, Linnen AM, Cardoso C, Joober R. Intranasal oxytocin attenuates the human acoustic startle response independent of emotional modulation. Psychophysiology. 2014 Nov;51(11):1169-77. doi: 10.1111/psyp.12263. Epub 2014 Aug 1.

  PMID: 25082371 BACKGROUND

• Frijling JL, van Zuiden M, Koch SB, Nawijn L, Veltman DJ, Olff M. Effects of intranasal oxytocin on amygdala reactivity to emotional faces in recently trauma-exposed individuals. Soc Cogn Affect Neurosci. 2016 Feb;11(2):327-36. doi: 10.1093/scan/nsv116. Epub 2015 Sep 17.

  PMID: 26382634 BACKGROUND

• Guastella AJ, Mitchell PB, Dadds MR. Oxytocin increases gaze to the eye region of human faces. Biol Psychiatry. 2008 Jan 1;63(1):3-5. doi: 10.1016/j.biopsych.2007.06.026. Epub 2007 Sep 21.

  PMID: 17888410 BACKGROUND

• Galovski TE, Blain LM, Chappuis C, Fletcher T. Sex differences in recovery from PTSD in male and female interpersonal assault survivors. Behav Res Ther. 2013 Jun;51(6):247-55. doi: 10.1016/j.brat.2013.02.002. Epub 2013 Mar 1.

  PMID: 23510841 BACKGROUND

• Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer-Lindenberg A. Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci. 2005 Dec 7;25(49):11489-93. doi: 10.1523/JNEUROSCI.3984-05.2005.

  PMID: 16339042 BACKGROUND

• Koch SB, van Zuiden M, Nawijn L, Frijling JL, Veltman DJ, Olff M. Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder. Neuropsychopharmacology. 2016 Jul;41(8):2041-51. doi: 10.1038/npp.2016.1. Epub 2016 Jan 7.

  PMID: 26741286 BACKGROUND

• Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E. Oxytocin increases trust in humans. Nature. 2005 Jun 2;435(7042):673-6. doi: 10.1038/nature03701.

  PMID: 15931222 BACKGROUND

• Macbeth AH, Stepp JE, Lee HJ, Young WS 3rd, Caldwell HK. Normal maternal behavior, but increased pup mortality, in conditional oxytocin receptor knockout females. Behav Neurosci. 2010 Oct;124(5):677-85. doi: 10.1037/a0020799.

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• Nawijn L, van Zuiden M, Koch SB, Frijling JL, Veltman DJ, Olff M. Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder. Soc Cogn Affect Neurosci. 2017 Feb 1;12(2):212-223. doi: 10.1093/scan/nsw123.

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• Palgi S, Klein E, Shamay-Tsoory SG. Oxytocin improves compassion toward women among patients with PTSD. Psychoneuroendocrinology. 2016 Feb;64:143-9. doi: 10.1016/j.psyneuen.2015.11.008. Epub 2015 Nov 17.

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• Rimmele U, Hediger K, Heinrichs M, Klaver P. Oxytocin makes a face in memory familiar. J Neurosci. 2009 Jan 7;29(1):38-42. doi: 10.1523/JNEUROSCI.4260-08.2009.

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• Theodoridou A, Rowe AC, Penton-Voak IS, Rogers PJ. Oxytocin and social perception: oxytocin increases perceived facial trustworthiness and attractiveness. Horm Behav. 2009 Jun;56(1):128-32. doi: 10.1016/j.yhbeh.2009.03.019. Epub 2009 Apr 1.

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• Wade D, Varker T, Kartal D, Hetrick S, O'Donnell M, Forbes D. Gender difference in outcomes following trauma-focused interventions for posttraumatic stress disorder: Systematic review and meta-analysis. Psychol Trauma. 2016 May;8(3):356-64. doi: 10.1037/tra0000110. Epub 2016 Feb 8.

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  PMID: 17987115 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Oxytocin

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Steven H Woodward, PhD

  VA Palo Alto Health Care System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinding of oxytocin drug container + randomization of oxytocin/placebo ordering over sessions
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized double-blind crossover design, in which all participants will undergo 2 sessions, receiving either oxytocin nasal spray or placebo nasal spray in random order.

Study Record Dates

• First Submitted: April 3, 2017
• First Posted: July 7, 2017
• Study Start: July 10, 2017
• Primary Completion: June 9, 2021
• Study Completion: June 9, 2021
• Last Updated: June 10, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)