Effects of Oxytocin Nasal Spray on Social Affiliation

Schizophrenia is a complex and heritable disorder that encompasses several clinical symptom domains and functional impairments. Existing treatments of schizophrenia, although effective against positive symptoms, fail to benefit negative symptoms, the focus of the current protocol. One of the strategies of novel drug development depends on identifying heritable physiological deficits that mark the disease liability and are thought to occur along the causal pathway of negative symptoms. These heritable physiological deficits are often found in the biological relatives of schizophrenia proband; particularly those who have schizophrenia related personality styles [defined by schizophrenia spectrum personalities (SSP) in the diagnostic system], even though they do not have the full-blown illness. The current protocol will pilot a strategy of targeting biomarkers of negative symptoms using intranasal oxytocin in relatives of schizophrenia patients. The drug probe studies in such non-clinical sample have several advantages including the absence of other drug treatment that may modulate the response, and the lack of generalized deficits causing problems with task comprehension/engagement that may mute the therapeutic signal. In addition, finding of efficacy of the experimental drug on the target physiological deficit and the associated symptoms has clinical implications on its own rights. This is because about 25% of subjects with schizophrenia spectrum personality disorders experience serious functional impairments.

Oxytocin is an extensively used drug, which is well tolerated with few serious side effects. Several lines of evidence suggest its putative role in the treatment of negatives symptoms, particularly a lack of social drive and related symptoms.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Oxytocin; Drug: Placebo

Detailed Description

The current study will examine the effects of intranasal oxytocin on physiological/cognitive markers of negative symptoms in 24 participants with schizophrenia spectrum traits. Subjects will be tested in two one-day studies carried out at least a month apart. Subjects will receive a 24 IU dose of intranasal oxytocin (or placebo) followed by a battery of cognitive/neurophysiological tests administered 50 minutes later completed over the next 155 minutes. A second dose of the drug (oxytocin or placebo) will be administered 2 hours after the 1st in order to maintain therapeutic plasma levels and to complete all testing.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Catonsville, Maryland, United States, 21228
      • Maryland Psychiatric Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male/Female subjects between ages of 18-64 years
• The presence of 3 or more SSP symptoms (at least 2 of the SSP symptoms will be negative symptoms as defined by the schizoid traits)
• The presence of visuo-spatial working memory impairment as defined by error in the oculomotor delayed response (ODR) task of more than 0.5 SD above the mean values in healthy control subjects
• Relative of an individual with schizophrenia, schizo-affective, or schizophreniform disorder
• Able to provide written informed consent. Females are excluded due to risk of discomfort and unblinding due to potential uterine cramps induced by oxytocin.

Exclusion Criteria:

• Subjects meeting criteria for a life-time diagnosis of any one of the DSM IV, Axis I psychotic disorders (exceptions being a single past episode of major depressive disorder with psychotic features or psychotic symptoms associated with substance abuse with the substance abuse ending 6-months prior to study participation) (this is for the SSP recruitment)
• Subjects meeting DSM-IV criteria for current alcohol or substance dependence (other than nicotine) within the last 6 months or DSM-IV criteria for alcohol or substance abuse (other than nicotine) within the last month
• Medical conditions that preclude participation in drug trials or assessments of outcome measures (including significant brain, cardiac, liver, lung, endocrinological or metabolic disorders)
• Received any investigational drug in the preceding four weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oxytocin, then Placebo; Participants first received 24IU of Oxytocin administered intranasally with 6 total sprays (three in each nostril) on the morning and at midday of one study visit. Then, after at least month the participants returned for a second study day and received placebo.	Drug: Oxytocin; 24 IU oxytocin (or Placebo) in a total of 6 puffs (3 puffs per nostril); Other Names: Pitocin; Syntocinon
Experimental: Placebo, then Oxytocin; Participants first received a placebo (saline nasal spray) administered intranasally with 6 total sprays (three in each nostril) on the morning and at midday of one study visit. Then, after at least month the participants returned for a second study day and received Oxytocin.	Drug: Placebo; Single dose (plus a booster dose) drug probe study using intranasal placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Social Affiliation Measured by Social Affiliative Role Play	In a videotaped session, research staff engages the participant in social interaction based on a role play. The tape is rated on social skills and on Positive and Negative Affect Scale. Participants are rated on a 5 point Likert scale ranging from very poor (1) to Very Good (5).	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hopkins Verbal Learning Test (HVLT)	HVLT comes in 6 different forms. Forms 4 and 5 were used for this study with one form administered on the first study day and the other on the second and were counterbalanced between subjects. Each form contains 12 nouns, four words each from one of three semantic categories, to be learned over the course of three learning trials.	15 minutes
Trust Game	Participants competed in a social trust game in which they are paired with a partner (the computer program). Over the course of 24 rounds the participant can offer up to $10 to their partner. The partner can either accept the offer, in which case the total amount offered is split equally between the participant and their partner (i.e. $10 is split into $5 each). Or the partner can reject the offer and receive an portion of the total offer for themselves and give the participant nothing ($0). The total amount of money that can be offered ranges from $0-240.	20 minutes
RVIP Reaction Times	Rapid Visual Information Processing (RVIP) measures primarily sustained attention but perhaps also working memory. The task was continuous stimuli presentation of a stream of single digits (from 1 to 9) presented in the center of the computer monitor at a rate of 1/600milliseconds; the subjects respond when they see a target sequence of 3 odds or 3 even digits in a consecutive sequence. Two target sequences are separated by a minimum of 5 and maximum of 30 non-target digits	25 minutes
Rapid Visual Information Processing Test (RVIP)	RVIP measures primarily sustained attention but perhaps also working memory. The task was continuous stimuli presentation of a stream of single digits (from 1 to 9) presented in the center of the computer monitor at a rate of 1/600ms; the subjects respond when they see a target sequence of 3 odds or 3 even digits in a consecutive sequence. Two target sequences are separated by a minimum of 5 and maximum of 30 non-target digits. There are a total of 48 target sequences during each test block. The number of correctly Identified target sequences or hits is recorded, as well as, false alarms (incorrectly identified target sequences) and reaction times.	25 minutes
Brief Assessments of Cognition for Schizophrenia	The BACS Symbol Coding subtest will be used to assess processing speed, and the demographically corrected T score, will be used for data analysis. This test requires less than 5 minutes to administer and provides a highly reliable measure of processing speed. There are nine symbols code 1 through 9. Participants are given 90 seconds to match a series of these symbols with their corresponding number. The total correct matches is the participants score. Scores range from 0-110.	5 minutes
Brief Smell Identification Test	The Brief Smell Identification Test (B-SIT) is a 5-minute, 12-item screening test. Participants try to identify 12 different odors with four multiple choice options given for each odor.	5 minutes
Reading the Mind in the Eyes	A 30 item task presents a picture of a person's eyes and the participant is ask to determine the person's mental state from 4 multiple choice options.	10 minutes
Facial Affect Recognition	This computer administered test includes 40 color photographs of four universal emotions (happy, sad, angry, and fearful) balanced for the posers gender, age, and ethnicity, including four low intensity and four high-intensity facial expressions of each emotion, plus 8 neutral faces. The stimuli are presented in random order and subjects are asked to identify which stimuli were presented to them at the end. Performance on this test correlates with negative symptom severity.	10 minutes

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: L E Hong, M.D., University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2009
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: April 17, 2008
• First Submitted That Met QC Criteria: April 19, 2008
• First Posted (Estimate): April 21, 2008

Study Record Updates

• Last Update Posted (Actual): September 9, 2019
• Last Update Submitted That Met QC Criteria: September 5, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Schizophrenia; relatives; Eye movements; phenotype; biochemical
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: HP-00043595; P50MH082999 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No