Daily Intranasal Oxytocin for Childhood-Onset Schizophrenia

Schizophrenia Clinical Trial

Official title:

The Use of Daily, Intranasal Oxytocin for the Treatment of Childhood-Onset Schizophrenia (COS), a Randomized Double-Blind Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01712646
• Other study ID #: 130004
• Secondary ID: 13-M-0004
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: October 20, 2012
• Last updated: July 6, 2017
• Start date: October 5, 2012

Study information

• Verified date: June 20, 2016
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background:

• Oxytocin is a chemical that the brain normally produces. It plays an important part in the way humans and other animals act in social and emotional situations. Adults with schizophrenia have been studied to see if oxytocin can reduce some symptoms of schizophrenia, such as hearing voices, feeling suspicious, and not feeling interested in daily life. These studies show that oxytocin may help. However, it has not been studied in children who develop schizophrenia. Researchers want to see if oxytocin, given as a nasal spray, is safe and can reduce schizophrenia symptoms in children.

Objectives:

• To see if an oxytocin nasal spray can reduce schizophrenia symptoms in children.

Eligibility:

• Children above 10 years of age who have childhood-onset schizophrenia, and have schizophrenia symptoms in spite of taking medication.

Design:

• This study will last 4 weeks. Participants will stay in the hospital for the entire period of the study. Participants may also have an extra 2 weeks of study medication and 1 week of testing immediately following the initial 4 weeks.

• Participants will be screened with a physical exam and medical and psychiatric history. They will provide blood and urine samples, and have imaging studies of the brain. They will also have tests to look at their social and emotional functioning. These tests will take 1 week to perform.

• Participants will have either oxytocin or placebo nasal spray twice daily for 2 weeks.

• At the end of the 2-week period with nasal spray, there will be 1 week with no nasal spray. All the tests of week 1 will be repeated.

• The optional extra 3 weeks (2 weeks with oxytocin and one week for testing) will be similar to the second, third, and fourth weeks of the study. All participants will have oxytocin during this period.

Description:

Background:

Recent studies with intranasal oxytocin administration indicate moderate efficacy in symptom reduction in adult patients with schizophrenia, and moderate to good response in improving social cognition in patients with autism. The majority (about 75%) of patients with childhood-onset schizophrenia (COS) continue to show impairing social and psychotic symptoms after drug treatment optimization, and almost 30% of children with COS have co-morbid autism spectrum disorder (ASD). Oxytocin may be a safe and effective adjunctive treatment to improve social cognition, reduce anxiety, and indirectly reduce psychotic symptoms in medication-stable COS patients.

Objective:

To study whether intranasal oxytocin (study medication) would be safe, improve emotional/social cognition, and reduce symptom severity in clinically stable COS children and whether the study medication would also result in specific neurocircuitry changes, as measured by multimodal neuroimaging.

Study Population:

72 patients (36 per group) with COS, ages 10 and above will be recruited. All patients will be on stable medications for at least one month prior to this study.

Design:

Two-week double-blind, placebo-controlled, parallel design trial of daily intranasal oxytocin. Subsequent to the study period, a two-week extension of open label study medication will be offered to all participants, regardless of study group assignment.

Outcome Measures:

Primary Outcome Measures:

To evaluate the safety of intranasal oxytocin in COS patients.

To assess whether intranasal administration of oxytocin will improve both positive and negative symptoms of schizophrenia compared to placebo, as measured by PANSS, SAPS, SANS, and BPRS.

To evaluate whether intranasal oxytocin has significant effects on the social and emotional processing and behavior of children with COS, as measured by the Diagnostic Analysis of Nonverbal Behavior (DANVA-2), Developmental Neuropsychological Assessment (NEPSY-2) standardized social perception battery, Brune Theory of Mind Pictures Stories Task, Reading the Mind in the Eyes Test. Social Responsiveness Scale (SRS).

To measure alterations in neurocircuitry after oxytocin administration, as measured by fMRI, DTI, and MEG.

To evaluate changes in blood plasma oxytocin levels measured over the course of the study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. primary completion date: June 20, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 99 Years

Eligibility

• INCLUSION CRITERIA:

COS patients (age 10 and above) recruited, enrolled, and diagnosed under the screening protocol 03-M-0035.

Have been stable on their medications for at least one month prior to enrollment in this study, with the exception of occasional use of prn (as needed) medication. There are no contraindications to oxytocin; therefore, all medications are permitted.

Continued problems in social/emotional domains, as evidenced by problems with interpersonal relationships (e.g., poor ability to relate with others, make friends, have meaningful social interactions), emotional processing (e.g., difficulty interpreting emotions, inappropriate emotional responses, significant anxiety around activities of daily living, lack of empathy), and/or residual symptoms of schizophrenia (e.g., hallucinations, delusions, flat affect, disorganized thinking/behavior), despite medication.

EXCLUSION CRITERIA:

Any major neurological illness (e.g., epilepsy, brain tumors, metabolic disorders).

Is pregnant, plans on becoming pregnant during the study, or is actively breast-feeding.

Related Conditions & MeSH terms

• Childhood Onset Psychotic Disorders
• Mental Disorders
• Psychotic Disorders
• Schizophrenia
• Schizophrenia, Childhood

Intervention

Drug:
• Intranasal Oxytocin

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Asarnow JR, Ben-Meir S. Children with schizophrenia spectrum and depressive disorders: a comparative study of premorbid adjustment, onset pattern and severity of impairment. J Child Psychol Psychiatry. 1988 Jul;29(4):477-88. — View Citation

Russell AT, Bott L, Sammons C. The phenomenology of schizophrenia occurring in childhood. J Am Acad Child Adolesc Psychiatry. 1989 May;28(3):399-407. — View Citation

Watkins JM, Asarnow RF, Tanguay PE. Symptom development in childhood onset schizophrenia. J Child Psychol Psychiatry. 1988 Nov;29(6):865-78. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood plasma oxytoxin levels
Primary	Neuocircuitry alterations in amygdale/cingulated
Primary	Brain activity alterations during exposure to social stimuli
Primary	Improved psychosis/anxiety symptoms
Primary	Improved DANVA-2/NEPSY-2/social interaction scores