Oxytocin and CBSST for People With Schizophrenia

This study is currently recruiting participants.
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

December 14, 2012
February 26, 2014
January 2014
December 2016   (final data collection date for primary outcome measure)
Determine if CBSST + oxytocin compared to CBSST + placebo is associated with improved social function. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Efficacy
Same as current
Complete list of historical versions of study NCT01752712 on ClinicalTrials.gov Archive Site
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 ]
Same as current
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
Same as current
 
Oxytocin and CBSST for People With Schizophrenia
Combined Oxytocin and CBSST for Social Function in People With Schizophrenia

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
  • Cognitive Behavioral Social Skills Training + Oxytocin
  • Cognitive Behavioral Social Skills Training + Placebo
  • 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)
  • Drug: CBSST with Placebo
    Matching placebo spray will be administered intranasally (10 puffs of the spray, 5 in each nostril at each administration);
  • Experimental: Cognitive Behavioral Social Skills Training + oxytocin
    Cognitive Behavioral Social Skills Training with adjunct oxytocin nasal spray treatment
    Intervention: Drug: CBSST with Oxytocin
  • Placebo Comparator: Cognitive Behavioral Social Skills Training + placebo
    Cognitive Behavioral Social Skills Training with placebo nasal spray
    Intervention: Drug: CBSST with Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
December 2016
December 2016   (final data collection date for primary outcome measure)

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
Both
18 Years to 55 Years
No
Contact: Jennifer Osing 410-402-6060 josing@mprc.umaryland.edu
United States
 
NCT01752712
HP-00054628
Yes
Robert W. Buchanan, M.D., University of Maryland
University of Maryland
University of California, San Diego
Principal Investigator: Robert Buchanan, MD University of Maryland
University of Maryland
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP