Oxytocin as Adjunctive Treatment of Schizophrenia

NCT01568528 | Completed Phase 2 Results DMC

• 1 other identifier: IRB00052127
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The focus of the current project is to advance our understanding of the effects of oxytocin (OT) on components of social cognition in schizophrenia (SCZ). Despite the rapid increase in our understanding of the role of OT in rodent models of social behavior and an explosion of interest in the prosocial effects of OT in healthy controls, little work has been done to dissect the potential effects of OT on SCZ subjects with social deficits. Social deficits are a crucial aspect of the functional impairments that limit the rehabilitation of patients with SCZ. In particular, SCZ patients with enduring negative symptoms (deficit syndrome, Kirkpatrick et al. 1989) have prominent social deficits as a core feature of this subtype of the illness. Our currently available medications do very little to improve these social deficits. Hence it is of utmost public health importance to address the knowledge gap regarding the potential of OT to improve social function in this illness. Intact social function depends on the competent functioning of several cognitive domains that subserve perception of social cues and the generation of motivated social behavior. We propose to conduct a pharmacological challenge study of OT vs. placebo administration to study the effects of OT on specific components of social cognition in male deficit syndrome SCZ subjects. Primary Hypothesis: Intranasal OT will improve social cognition in subjects with deficit syndrome SCZ.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (5)

• Eye Tracking: Fixation Count

  In order to assess the processing of social stimuli, subjects will be presented with a series of human faces of mixed sex and race showing neutral emotions and instructed to visually scan each face. Six regions of interest (ROIs) will be defined for each face stimulus: eyes, nose mouth, forehead, cheeks, and outside the contours of the face. The data will be processed off line for each face stimulus as the total time of fixation inside each of the ROIs. Refers to the number of fixations that occurred on the face of the stimulus presented to the participant during the eye-tracking assessment.

  Day 1

• Eye Tracking: Dwell Duration Time

  Refers to the amount of time that an individual spent looking at the face of the stimulus presented to the participant during the eye-tracking assessment.

  Day 1

• Social Reward Ball-tossing Task

  Subjects will perform a computerized Social Reward Ball-Tossing Task in which they decide to return the ball to one of three fictional partners. The photos of the partners and their reciprocity in returning the ball to the subject will be manipulated. The number of balls sent to each of the partners will be quantified to assess socially reinforced learning. The result is expressed in number of ball tosses sent to the subject by a fictional player with a positive expression MINUS the number of ball tosses sent to the subject by a fictional player with a negative expression. These measures will be compared between the control subjects, oxytocin and placebo group.

  Day 1

• Non-Social Reward Ball-tossing Game

  Social reward trials will be interleaved with non-social trials where subjects will play with random geometric shapes or landscape scenes associated with positive and negative non-social rewards. The outcome measure reported herein is the number of ball tosses the subject sends to shape A minus the number of ball tosses sent to shape B.

  Day 1

• Facial Emotion Identification Task

  The stimuli are 19 standard black and white pictures of faces showing one of six different emotions (happy, sad, angry, surprise, disgusted, ashamed) that were developed by Ekman and Friesen (1976). The pictures are shown for 15 sec, with 10 sec between each face. After the presentation of each face the subject is asked to choose which of the six emotions was displayed. The score on the test is the sum of correct responses. Subjects in the two groups (oxytocin vs. placebo) will be compared.

  Day 1

Study Arms (3)

Oxytocin

EXPERIMENTAL

The intranasal oxytocin intervention will be the administration of OT intranasally at a dose of three 4 IU puffs per nostril for a total dose of 24 IU. Each puff is 0.1ml in volume so the total volume administered will be 0.6 ml intranasally. This dose has been used in a number of other similarly designed challenge studies examining the effects of a single dose of OT (Kirsch et al. 2005; Kosfeld et al. 2005; Guastella et al. 2008a; Guastella et al. 2008b; Rimmele et al. 2009; Andari et al. 2010).

Drug: Oxytocin

Placebo

PLACEBO COMPARATOR

Intranasal placebo The PBO/control will consist of the OT vehicle administered as three puffs in each nostril. Each puff is is 0.1ml in volume so the total volume administered will be 0.6 ml intranasally. Treatment assignment will be by random allocation in blocks of six. Both experimenters and subjects will be blind to the treatment they are receiving.

Drug: Placebo

Healthy Controls

OTHER

Participants who have no psychiatric diagnosis and will be controls for this project. These controls will not receive oxytocin or placebo. They will only receive psychiatric screening interview, MATRICS Consensus Cognitive Battery (MCCB) assessment, urine drug screen, vision testing, and the three social cognition tasks.

Other: Control

Interventions

Oxytocin DRUG

OT intervention will be administration of OT intranasally at a dose of three 4 IU puffs per nostril for a total dose of 24 IU. This dose has been used in a number of other similarly designed challenge studies examining the effects of a single dose of OT (Kirsch et al. 2005; Kosfeld et al. 2005; Guastella et al. 2008a; Guastella et al. 2008b; Rimmele et al. 2009; Andari et al. 2010).

Also known as: Syntocinon

Oxytocin

Placebo DRUG

The PBO/control will consist of the OT vehicle only delivered as 3 puffs of saline per nostril for a total of 6 puffs. Each puff contains 0.1 ml in volume, so the total delivered will be 0.6 ml intranasally.

Also known as: Inactive vehicle

Placebo

Control OTHER

Participants who have no psychiatric diagnosis and will be controls for this project. These controls will NOT receive oxytocin or PBO. They will only receive psychiatric screening interview, MCCB Consensus Cogntive Battery assessment, urine drug screen, vision testing, and the three social cognition tasks.

Healthy Controls

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be between 18 and 65 years old at the time of study screening.
• Subjects must demonstrate adequate decisional capacity, in the judgment of the consenting study staff member, to make a choice about participating in this research study.
• Subjects must have been psychiatrically and medically stable for 8 weeks prior to consent in the judgment of the Principal Investigator.
• Subjects must have been maintained on a stable treatment of antipsychotics and/or other concomitant psychotropic treatment for at least 6 weeks prior to consent.
• Subjects must have no more than a moderate severity rating on hallucinations and unusual thought content as shown by a score of ≤ 4 on the Positive and Negative Symptoms Scale (PANSS).
• Subjects must be able to validly complete the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), in the judgment of the consenting study staff person.
• Subjects must have the visual, auditory, and motor capacity to use the computer software in the judgment of the consenting study staff person. Visual acuity must be at least 20/30 corrected.
• Subjects must have a minimal level of extrapyramidal symptoms as shown by a Simpson-Angus Scale total score of no more than 6.
• Subjects must have a minimal level of depressive symptoms as shown by a Calgary Depression Scale (CDSS) total score of no more than 10.

You may not qualify if:

• Female sex
• History of bipolar disorder
• Active substance dependence within the prior 30 days (cigarette smoking is allowed)
• Has had a psychiatric hospitalization in the 8 weeks prior to consent.
• Suicidal or homicidal ideation in the previous six months
• Subjects who have answered 'yes' to Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the Columbia-Suicide Severity Rating Scale, C-SSRS, or who have answered 'yes' to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act or behavior) on the C-SSRS "Suicidal Behavior" portion shall be excluded from the study if ideation or behavior occurred within one month of consent. Subjects excluded for this reason will be referred for appropriate treatment.
• History of mental retardation or pervasive developmental disorder
• History of neurological disorder (e.g., traumatic brain injury, seizure disorder, Parkinson's Disease, dementia), loss of consciousness for more than 10 minutes due to head trauma, known HIV infection, or AIDS
• Treatment with a benzodiazepine in the two weeks prior to consent.
• Control Participants:
• Male
• Ages 18-65
• Female
• History of a psychotic disorder, or depression requiring medication
• Active substance abuse or dependence within the prior 30 days

Sponsors & Collaborators

• Emory University: lead
• Atlanta VA Medical Center: collaborator

Study Sites (1)

Atlanta VA Medical Center

Decatur, Georgia, 30033, United States

Location

Related Publications (5)

• Young LJ, Murphy Young AZ, Hammock EA. Anatomy and neurochemistry of the pair bond. J Comp Neurol. 2005 Dec 5;493(1):51-7. doi: 10.1002/cne.20771.

  PMID: 16255009 BACKGROUND

• Andari E, Duhamel JR, Zalla T, Herbrecht E, Leboyer M, Sirigu A. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4389-94. doi: 10.1073/pnas.0910249107. Epub 2010 Feb 16.

  PMID: 20160081 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

• Mueser KT, Doonan R, Penn DL, Blanchard JJ, Bellack AS, Nishith P, DeLeon J. Emotion recognition and social competence in chronic schizophrenia. J Abnorm Psychol. 1996 May;105(2):271-5. doi: 10.1037//0021-843x.105.2.271.

  PMID: 8723008 BACKGROUND

• Andari E, Massa NM, Fargotstein MD, Taylor NB, Halverson DM, Owens AV, Currin DL, Bhattacharya A, Gitman D, Cuthbert BC, Young LJ, Duncan EJ. Effects of Oxytocin on Emotion Recognition in Schizophrenia: A Randomized Double-Blind Pilot Study. J Clin Psychopharmacol. 2021 Mar-Apr 01;41(2):103-113. doi: 10.1097/JCP.0000000000001367.

  PMID: 33587397 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

Oxytocin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic 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

Results Point of Contact

• Title: Dr. Erica Duncan
• Organization: Emory University

eduncan@emory.edu

404-321-6111

Study Officials

• Erica J Duncan, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 28, 2012
• First Posted: April 2, 2012
• Study Start: March 1, 2013
• Primary Completion: March 15, 2017
• Study Completion: March 15, 2017
• Last Updated: September 4, 2019
• Results First Posted: September 4, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)