Oxytocin and CBSST for People With Schizophrenia

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of Maryland
Sponsor:
Collaborator:
University of California, San Diego
Information provided by (Responsible Party):
Robert W. Buchanan, M.D., University of Maryland
ClinicalTrials.gov Identifier:
NCT01752712
First received: December 14, 2012
Last updated: February 26, 2014
Last verified: February 2014
  Purpose

A significant proportion of people with schizophrenia are characterized by impaired ability to socially engage with others, which may reflect social aversion secondary to defeatist beliefs; decreased motivation for social interactions; and/or impairment in the normal reinforcement value of social interactions. These impairments in social function have been shown to be associated with social skill deficits; and decreased ability to identify and remember emotional facial expressions and empathize with the emotional status of others. Unfortunately, pharmacological interventions have limited benefits for impaired social function, whereas psychosocial interventions provide only partial benefit for this critical aspect of the illness. The development of an effective intervention for functional outcomes remains a central therapeutic challenge. Cognitive Behavioral Social Skills Training (CBSST) uses corrective feedback and reinforcement provided by successful interactions to challenge and reduce defeatist performance beliefs that contribute to low drive and interfere with social functioning. CBSST has been shown to have modest effects on social function in people with schizophrenia. Oxytocin plays a critical role in the regulation of normal social affiliative behavior; it is hypothesized to enhance social affiliation through the reduction of anxiety or social risk aversion; the enhancement of motivation for prosocial approach behavior; and/or increased modulation of the salience and processing of social cues. People with schizophrenia have decreased oxytocin levels, which are associated with an impaired ability to identify facial emotions and decreased prosocial behaviors. The addition of oxytocin to CBSST is hypothesized to: 1) enhance the reduction of defeatist performance beliefs by reducing social risk aversiveness and avoidance; 2) enhance social skill acquisition through improvement of proximal social behaviors; and 3) facilitate the translation of learned social skills into community practice through its effects on prosocial attachment behaviors and reduction in social disinterest. The investigators will conduct a 24-week, double-blind, placebo-controlled, RCT with a 3-month follow-up evaluation. The primary aim of the study is to collect preliminary data on the efficacy of combined CBSST + oxytocin for social function in schizophrenia. Secondary aims include the examination of the safety and acceptability of the proposed intervention. The investigators will also examine whether the effects of the proposed intervention are mediated by reduced defeatist performance beliefs; increased ability to trust others; and/or improved performance on measures of facial recognition and memory. Finally, in an exploratory framework, the investigators will examine the effects of the proposed intervention on symptoms, neuropsychological test performance, and global clinical improvement.


Condition Intervention
Cognitive Behavioral Social Skills Training + Oxytocin
Cognitive Behavioral Social Skills Training + Placebo
Drug: CBSST with Oxytocin
Drug: CBSST with Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Combined Oxytocin and CBSST for Social Function in People With Schizophrenia

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Determine if CBSST + oxytocin compared to CBSST + placebo is associated with improved social function. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Efficacy


Secondary Outcome Measures:
  • Determine if CBSST + oxytocin compared to CBSST + placebo is associated with increased incidence of side effects. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Determine if CBSST + oxytocin compared to CBSST + placebo is associated with reduced social aversion, including social disinterest and defeatist performance beliefs; increased ability to trust others; and/or improved performance on facial recognition and [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Change Mechanism


Estimated Enrollment: 60
Study Start Date: January 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cognitive Behavioral Social Skills Training + oxytocin
Cognitive Behavioral Social Skills Training with adjunct oxytocin nasal spray treatment
Drug: CBSST with Oxytocin
The oxytocin dose of 80 IU/day, will be administered in two divided doses: 40 IU in the morning and 40 IU in the evening. Oxytocin will be administered intranasally (10 puffs of the spray, 5 in each nostril at each administration)
Placebo Comparator: Cognitive Behavioral Social Skills Training + placebo
Cognitive Behavioral Social Skills Training with placebo nasal spray
Drug: CBSST with Placebo
Matching placebo spray will be administered intranasally (10 puffs of the spray, 5 in each nostril at each administration);

  Hide Detailed Description

Detailed Description:

A NIMH mission priority is the development of new and better interventions, whose focus extends beyond symptom amelioration to the development of interventions that allow people who suffer from severe mental illnesses "to live full and productive lives" (NIMH Strategic Plan, 2008). In particular, the NIMH Strategic Plan notes the importance of translating "research on the biological causes of disorder to inform and develop psychosocial and biomedical interventions that target core features of disease, assess outcomes appropriate to the course of illness under study, and develop study designs that have impact on these features." The current proposal is built upon the observations that: 1) people with schizophrenia are characterized by marked impairments in their social function; 2) current pharmacological treatments do not address these impairments; 3) CBSST has been shown to have modest effects on social function in people with schizophrenia. This limited efficacy may be related to the lack of interest or drive people with schizophrenia have for social interactions; 4) oxytocin plays a critical role in normal social affiliative behavior through a) the reduction of anxiety or social risk aversion, b) the enhancement of motivation for prosocial approach or affiliative behavior, and/or c) increased modulation of the salience and processing of social cues; and 5) decreased oxytocin is associated with social function impairments in people with schizophrenia.

The proposed study is based on the proposition that the use of a pharmacological agent, whose behavioral effects compliment the psychological mechanisms of action of a psychosocial intervention, is an important adaptation of an intervention previously shown to have moderate effects on social function. The addition of oxytocin to CBSST is hypothesized to: 1) enhance the reduction of defeatist performance beliefs by reducing social risk aversiveness and avoidance, which would increase exposure to reinforcement and corrective feedback; 2) enhance social skill acquisition through improvement of proximal social behaviors, e.g. making eye contact and attending to the facial expressions of social partners; and 3) facilitate the translation of learned social skills into community practice through its effects on prosocial attachment behaviors, reduction in social disinterest, and effects on distal behaviors, e.g. initiating conversations and responding to social invitations. Increased social risk taking within and between sessions would expose participants to a greater frequency of positive feedback and success experiences, which would provide evidence to dispute their defeatist beliefs and social disinterest attitudes. In addition, increased social risk taking could improve homework adherence (e.g., practicing talking to people in the community) and engagement in new community activities. These interactive effects would subsequently lead to a substantial improvement in CBSST efficacy for social function. Ultimately, the importance of improved social function is the effect that such improvement would have on overall levels of health and functioning, including vocational outcome.

The proposed study will enable us to collect preliminary data on the acceptability, efficacy, feasibility, and safety of the proposed intervention. In particular, this would be the first study to examine the safety of long-term oxytocin in this population. The study will also provide critical data on the feasibility of recruiting and retaining participants with schizophrenia in a long-term intervention, which combines two different therapeutic modalities: CBSST and oxytocin. If found to be efficacious, feasible, and well-tolerated, we will plan to conduct a larger study, which would include the use of cognitive and imaging biomarkers, to more fully elucidate the mechanism of action of the observed treatment effects. The investigators will address the following specific aims:

Aim #1 (Efficacy): To determine if CBSST + oxytocin compared to CBSST + placebo-oxytocin is associated with improved social function.

Aim #2 (Safety): To determine if CBSST + oxytocin compared to CBSST + placebo-oxytocin is associated with increased incidence of side effects.

Aim #3 (Change Mechanism): To determine if CBSST + oxytocin compared to CBSST + placebo-oxytocin is associated with reduced social aversion, including social disinterest and defeatist performance beliefs; increased ability to trust others; and/or improved performance on facial recognition and memory measures.

Aim #4 (Other Outcomes): To determine if CBSST + oxytocin compared to CBSST + placebo-oxytocin is associated with improved neuropsychological test performance, and/or decreased positive, negative, and/or anxiety/depression symptoms, and clinical global improvement.

  Eligibility

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

Inclusion Criteria:

  1. DSM-IV-TR diagnosis of schizophrenia
  2. Scale for the Assessment of Negative Symptoms asociality item score ≥ 2
  3. Considered clinically stable by the treating psychiatrist
  4. Stable treatment with the same antipsychotic for at least 60 days and the same dose for at least the 30 days prior to study entry.

Exclusion Criteria:

  1. Organic brain disorder, including cerebrovascular accident; epilepsy; traumatic brain injury, loss of consciousness (LOC) for more than 30 minutes
  2. Mental retardation
  3. Medical conditions, whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol
  4. Participant is pregnant or is lactating
  5. History of chronic allergic rhinitis
  6. DSM-IV-TR diagnosis of alcohol or substance dependence (except nicotine) within the last 6 months, or participant has met dependence criteria for 5 years or more.
  7. DSM-IV-TR diagnosis of alcohol or substance abuse (except nicotine) within the last month
  8. Participant has a past history of polydypsic hyponatremia (defined by sodium levels below 130 mmol/L) or has a current sodium level below 135 mmol/L
  9. Participant with EKG evidence of any of the following cardiac arrhythmias: QTc prolongation (Males: 450 msec or greater; females: 470 msec or greater); atrial fibrillation; ventricular or supraventricular tachycardia; and 2nd or 3rd degree A-V Block
  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: NCT01752712

Contacts
Contact: Jennifer Osing 410-402-6060 josing@mprc.umaryland.edu

Locations
United States, Maryland
Maryland Psychiatric Research Center Recruiting
Baltimore, Maryland, United States, 21228
Contact: Chris Brown    410-402-7878    Cbrown@mprc.umaryland.edu   
Contact: Jennifer Osing    410-402-6060    josing@mprc.umaryland.edu   
Principal Investigator: Robert W. Buchanan, M.D.         
Sponsors and Collaborators
University of Maryland
University of California, San Diego
Investigators
Principal Investigator: Robert Buchanan, MD University of Maryland
  More Information

No publications provided

Responsible Party: Robert W. Buchanan, M.D., Chief, Maryland Psychiatric Research Center, Outpatient Research Program, University of Maryland
ClinicalTrials.gov Identifier: NCT01752712     History of Changes
Other Study ID Numbers: HP-00054628
Study First Received: December 14, 2012
Last Updated: February 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Maryland:
Oxytocin
Social function
CBSST

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 19, 2014