Oxytocin as Adjunctive Treatment of Schizophrenia

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Emory University
Sponsor:
Collaborator:
Atlanta VA Medical Center
Information provided by (Responsible Party):
Erica Duncan, MD, Emory University
ClinicalTrials.gov Identifier:
NCT01568528
First received: March 28, 2012
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention
Schizophrenia
Drug: Oxytocin
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Oxytocin as Adjunctive Treatment of Schizophrenia

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • eye tracking [ Time Frame: within two hours after administration of oxytocin vs. placebo ] [ Designated as safety issue: No ]
    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. The initial analysis will compare time spent by subjects after oxytocin vs. placebo looking at the ROIs within vs. outside the facial contours.


Secondary Outcome Measures:
  • Social reward ball-tossing task [ Time Frame: within two hours after administration of oxytocin vs. placebo ] [ Designated as safety issue: No ]
    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. These 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 number of balls sent to each of the partners will be quantified to assess socially reinforced learning. These measures will be compared between the oxytocin and placebo group.


Other Outcome Measures:
  • Facial Emotion Identification Task [ Time Frame: within two hours after administration of oxytocin vs. placebo ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 40
Study Start Date: March 2013
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oxytocin
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
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).
Other Names:
  • Syntocinon
  • Oxytocin
Placebo Comparator: Placebo

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
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.
Other Names:
  • Placebo
  • Inactive vehicle

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Subjects for the study will be forty male VA patients with a diagnosis of schizophrenia. Diagnosis will be determined using the Structured Clinical Interview for DSM-IV Axis I Disorders/SCID-P (Spitzer et al. 1992). Subjects must be categorized as having a primary deficit syndrome on the Kirkpatrick Schedule for the Deficit Syndrome (Kirkpatrick et al. 1989).

Additional inclusion criteria:

  1. Subjects must be between 18 and 55 years old at the time of study screening.
  2. 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.
  3. Subjects must have been psychiatrically and medically stable for 8 weeks prior to consent in the judgment of the Principal Investigator.
  4. 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.
  5. 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).
  6. 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.
  7. 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.
  8. Subjects must have a minimal level of extrapyramidal symptoms as shown by a Simpson-Angus Scale total score of no more than 6.
  9. Subjects must have a minimal level of depressive symptoms as shown by a Calgary Depression Scale (CDSS) total score of no more than 10.

Exclusion criteria:

  1. Female sex
  2. History of bipolar disorder
  3. Active substance dependence within the prior 30 days (cigarette smoking is allowed)
  4. Has had a psychiatric hospitalization in the 8 weeks prior to consent.
  5. Suicidal or homicidal ideation in the previous six months
  6. 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.
  7. History of mental retardation or pervasive developmental disorder
  8. 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
  9. Treatment with a benzodiazepine in the two weeks prior to consent.
  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: NCT01568528

Contacts
Contact: Molly Fargotstein, BA 404-321-6111 ext 6967 molly.fargotstein@va.gov
Contact: Erica J Duncan, MD 404-321-6111 ext 7532 erica.duncan@va.gov

Locations
United States, Georgia
Atlanta VA Medical Center Recruiting
Decatur, Georgia, United States, 30033
Contact: Molly Fargotstein, BA    404-321-6111 ext 6967    molly.fargotstein@va.gov   
Contact: Erica J Duncan, MD    404-321-6111 ext 7532    erica.duncan@va.gov   
Principal Investigator: Erica J Duncan, MD         
Atlanta VA Medical Center Recruiting
Decatur, Georgia, United States, 30033
Contact: Erica Duncan, MD    404-321-6111 ext 7532    erica.duncan@va.gov   
Principal Investigator: Erica Duncan, MD         
Sponsors and Collaborators
Emory University
Atlanta VA Medical Center
Investigators
Principal Investigator: Erica J Duncan, MD Emory University
  More Information

Publications:
Responsible Party: Erica Duncan, MD, Associate Professor, Emory University
ClinicalTrials.gov Identifier: NCT01568528     History of Changes
Other Study ID Numbers: IRB00052127
Study First Received: March 28, 2012
Last Updated: April 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Oxytocin
Oxytocics
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014