Study of the Effects of Oxytocin on Attentional Bias and Startle in PTSD - Full Text View

Purpose

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.

Condition	Intervention	Phase
Posttraumatic Stress Disorder	Drug: Oxytocin Drug: Placebos	Early Phase 1


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Crossover Assignment Intervention Model Description: 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. Masking: Participant, Investigator, Outcomes Assessor Masking Description: Blinding of oxytocin drug container + randomization of oxytocin/placebo ordering over sessions Primary Purpose: Basic Science
Official Title:	Placebo-Controlled Study of the Effects of Oxytocin on Attentional Bias and Startle in PTSD

Resource links provided by NLM:

Drug Information available for: Oxytocin

U.S. FDA Resources

Further study details as provided by Palo Alto Veterans Institute for Research:

Primary Outcome Measures:

Change in attentional bias [ Time Frame: 1-2 weeks ]
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
Change in startle response -heart rate [ Time Frame: 1-2 weeks ]
Difference between oxytocin vs. placebo lab sessions in the magnitude of pre-to-post startle stimulus change in heart rate

Other Outcome Measures:

Change in startle response -EDA [ Time Frame: 1-2 weeks ]
Difference between oxytocin vs. placebo lab sessions in the magnitude of pre-to-post startle stimulus change in AC-coupled electrodermal activity at the hand
Change in startle response -EMG [ Time Frame: 1-2 weeks ]
Difference between oxytocin vs. placebo lab sessions in the magnitude of pre-to-post startle stimulus change in corrugator electromyography


Estimated Enrollment:	40
Anticipated Study Start Date:	July 10, 2017
Estimated Study Completion Date:	July 31, 2019
Estimated Primary Completion Date:	February 28, 2019 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Immediate Oxytocin 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 single-dose administration of OT nasal spray, complete computer-based tasks post-dose for approximately 1 hour Other Name: syntocinon Drug: Placebos single-dose administration of placebo nasal spray, complete computer-based tasks post-dose for approximately 1 hour
Placebo Comparator: Delayed Oxytocin 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 single-dose administration of OT nasal spray, complete computer-based tasks post-dose for approximately 1 hour Other Name: syntocinon Drug: Placebos single-dose administration of placebo nasal spray, complete computer-based tasks post-dose for approximately 1 hour

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Eligibility


Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	Male
Gender Based Eligibility:	Yes
Gender Eligibility Description:	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.
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

US military Veteran
Current posttraumatic stress disorder
Medically healthy

Exclusion Criteria:

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03211013

Contacts


Contact: Steven H Woodward, PhD	650-493-5000 ext 22111	steve.woodward@va.gov
Contact: Ned J Arsenault, BA	650-493-5000 ext 27120	ned.arsenault@va.gov

Locations


United States, California
VA Palo Alto Health Care System	Recruiting
Menlo Park, California, United States, 94025
Contact: Research Assistant 650-493-5000 ext 27826

Sponsors and Collaborators

Palo Alto Veterans Institute for Research

Investigators


Principal Investigator:	Steven H Woodward, PhD	VA Palo Alto Health Care System

More Information

Publications:

Nagasawa M, Mitsui S, En S, Ohtani N, Ohta M, Sakuma Y, Onaka T, Mogi K, Kikusui T. Social evolution. Oxytocin-gaze positive loop and the coevolution of human-dog bonds. Science. 2015 Apr 17;348(6232):333-6. doi: 10.1126/science.1261022. Epub 2015 Apr 16.

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.

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.

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.

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.

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.

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. Epub 2006 Nov 29.

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.

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.

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. Epub 2007 Sep 21.

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.

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.

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.

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

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.

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.

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.

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.

Rubenstein DA, Debboun M, Burton R. Canine-assisted therapy in military medicine. Perspectives: commander's introduction. US Army Med Dep J. 2012 Apr-Jun:1-4.

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.

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.

Zak PJ, Stanton AA, Ahmadi S. Oxytocin increases generosity in humans. PLoS One. 2007 Nov 7;2(11):e1128.


Responsible Party:	Palo Alto Veterans Institute for Research
ClinicalTrials.gov Identifier:	NCT03211013 History of Changes
Other Study ID Numbers:	WOS0022ADM
Study First Received:	April 3, 2017
Last Updated:	July 5, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No


Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Palo Alto Veterans Institute for Research:


oxytocin PTSD attention bias startle

Additional relevant MeSH terms:


Stress Disorders, Post-Traumatic Stress Disorders, Traumatic Trauma and Stressor Related Disorders Mental Disorders	Oxytocin Oxytocics Reproductive Control Agents Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 11, 2017