Schizophrenia
Conditions
Keywords
Oxytocin
Brief summary
Schizophrenia has a devastating and disproportionate effect on veterans compared to the general US population. Some of the most disabling symptoms, such as low motivation, difficulty expressing emotions, and decreased ability to infer the mental states of others, cause poor social functioning. This means that veterans with schizophrenia have trouble navigating interpersonal interactions and building meaningful relationships in the community. Unfortunately, current antipsychotic medications typically only improve positive symptoms but fail to improve social functioning deficits, which are strong predictors of poor quality of life and functional outcomes. Oxytocin, a peptide found in the brain, plays an important role in social behavior and is known to moderate affiliation, stress, and learning across taxa. In this study, the investigators will test whether oxytocin could be an effective treatment for social functioning deficits in schizophrenia. The investigators will examine changes in brain activation to understand how oxytocin affects behavior and to predict which individuals may benefit from oxytocin treatment.
Detailed description
The study uses a combined within- and between-subject placebo-controlled study design. Within subjects phase: After screening, participants will be randomized into two study arms for the fMRI phase of the study. In each study arm, participants will complete a placebo-controlled, within-subject, pharmaco-fMRI paradigm with one of two possible dosages of oxytocin (20 or 40IU) and placebo. Following the fMRI phase of the study, participants will be randomized for the next phase of the study Between subjects phase: Participants will receive the same dosage of oxytocin the participant received in the fMRI phase, or placebo, twice daily for 3 weeks. Before and after the three weeks of drug administration, participants will be assessed for social functioning, social ability, negative symptoms, and theory of mind. More participants will be randomized to receive chronically administered oxytocin than placebo to maximize the study's power to test the investigators' hypothesis that acute oxytocin-induced increases in right temporo-parietal junction activity will be positively correlated with improvements in social functioning (primary outcome), social ability, negative symptoms, and theory of mind over three weeks of oxytocin administration.
Interventions
DRUGOxytocin
Intranasal administration of oxytocin
DRUGPlacebo
Placebo
Sponsors
VA Office of Research and Development
University of California, San Francisco
VA Greater Los Angeles Healthcare System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double Blind
Intervention model description
The study uses a combined within- and between-subject placebo-controlled study design. After screening, participants will be randomized into two study arms for the fMRI phase of the study. In each study arm, participants will complete a placebo-controlled, within-subject, pharmaco fMRI paradigm with one of two possible dosages of oxytocin (20 or 40IU) and placebo. 75 participants will be randomized to receive 20IU oxytocin and placebo and 75 will be randomized to receive 40IU oxytocin and placebo, with the order of administration randomized and separated by two weeks. Following the fMRI phase of the study, participants will be randomized to receive the same dosage of oxytocin the participant received in the fMRI phase, or placebo, twice daily for 3 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Veteran * age 18-70 * a diagnosis of schizophrenia, schizophreniform, schizoaffective, or brief psychotic disorder determined by the Structured Clinical Interview for DSM-5 * no medication changes or psychiatric hospitalizations in the past month * SFS modified raw score of no more than 75
Exclusion criteria
* substance use disorder in the past month, except mild to moderate cannabis use disorder * illness affecting the nasal passages * significant neurological/medical disorder * pacemakers * extensive dental work * claustrophobia * deafness * inability to read * currently participating in a psychosocial intervention targeting social functioning deficits * currently taking high dose testosterone or estrogen/progesterone * inability to complete VOT
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Social Functioning Score | Baseline visit: Full assessment is collected prior to any treatments fMRI phase: assessment not collected Chronic phase: partial assessment collected before the start (A1) and at end (A2) of 3 weeks of daily administration | The Social Functioning Scale is a 79-item semi-structured interview based assessment that includes \[a global summary score (primary outcome)\] The subscale scores of social engagement, interpersonal communication, and prosocial were expected the change in 3 weeks, while other subscales were not expected to change (e.g. employment) and thus were not collected during the chronic period. Scale ranges from 0 to lower functioning to 90 higher functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CAINS Score (Clinical Assessment Interview for Negative Symptoms) | Baseline visit: assessment is collected prior to any treatments fMRI phase: assessment not collected Chronic phase: assessment collected before the start (A1) and at end (A2) of 3 weeks of daily administration | Negative symptoms will be assessed with the CAINS (clinical assessment interview for negative symptoms) comprised of several subscales that will be summed for a global score. Each item is assessed from 0-no impairment to 4-severe deficit. The total score from 0 to 52 where higher scores represent more significant impairment. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJosh Woolley, BS
San Francisco VA Medical Center, San Francisco, CA
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 53 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 2 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 | 0 / 6 | 0 / 3 | 0 / 2 | 0 / 2 | 0 / 6 | 0 / 3 |
| other Total, other adverse events | 0 / 2 | 0 / 2 | 1 / 6 | 0 / 3 | 0 / 2 | 0 / 2 | 1 / 6 | 0 / 3 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 | 0 / 6 | 0 / 3 | 0 / 2 | 0 / 2 | 0 / 6 | 0 / 3 |
Outcome results
None listed