Clinical trial NCT00506909: Oxytocin Add on Study for Stable Schizophrenic Patients
Official title: Double-Blind, Randomized, Placebo-Controlled, Cross-Over Study of Intranasal Oxytocin Augmentation of Antipsychotic Medication in Schizophrenia Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Schizophrenia
Keywords: oxytocin
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
First posted: 2007-07-25
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The objective of the study is to compare the efficacy of intranasal oxytocin versus intranasal placebo to improve symptoms in schizophrenia patients who have residual symptoms despite being on adequate treatment with antipsychotic medication.

Detailed description: Schizophrenia patients treated with even the best currently available antipsychotic drugs continue to experience significant symptoms. There is a strong need for better treatments including treatments that can safely be given as adjunct to current antipsychotics in order to improve overall efficacy of treatment.

Oxytocin is a neurohypophyseal peptide best known for its role as a neurohormone involved in parturition and lactation. In addition to these well established peripheral effects, there is a compelling body of converging evidence indicating that oxytocin plays a critical role in the regulation of a number of diverse centrally-mediated behavioral and cognitive processes that are highly relevant to Schizophrenia, including social attachment and memory , (see Argiolas and Gessa 1990; McCarthy and Aaltemus 1997).Furthermore, several lines of research suggest that oxytocin receptors may be an important target for development of novel treatments for schizophrenia. Oxytocin and its receptors exist in several areas of the brain which have been heavily implicated in the pathophysiology of schizophrenia, such as the nucleus accumbens and the hippocampus, (Van Leeuwan et al 1985). Oxytocin administered peripherally inhibits dopamine transmission in the mesolimbic pathway (Sarnyai 1992) et al, 1990). Antipsychotics have been found to elevate the secretion of oxytocin in rats (Uvnas-Moberg et al 1992a) suggesting that endogenous oxytocin may play a role in the therapeutic effects of antipsychotic drugs.

Each subject will be enrolled for 6 week treatment period after a screening phase Study procedure involves weekly clinic visits as an outpatient. Forty patients will be randomly assigned to either 40 IU oxytocin twice daily or vehicle placebo. After 3 weeks, treatments will be crossed over such that subjects that received oxytocin will receive placebo and vice versa. The study ratio is 1:1. Dose of oxytocin is based upon previous studies in humans showing improvement in schizophrenia related changes in behavior and brain function (Kosfeld et al, 2005; Kirsch 2005; Heinrich M 2003).

The total study duration for each individual subject will be approximately 7 weeks, which includes up to 7-day screening period, a baseline (randomization) visit, three week treatment period, 1 week washout, baseline, and three weeks cross over treatment.

Eligibility criteria: Inclusion Criteria:

1. Adult men or women, 18 years of age or older.
2. Meet DSM-IV criteria for Schizophrenia.
3. Women of childbearing potential must test negative for pregnancy at the time of enrollment based on urine pregnancy test and agree to use a reliable method of birth control during the study.
4. Must be on a therapeutic dose of an atypical antipsychotic medication (examples but not limited to Clozapine Olanzapine, Risperidone, Ziprasidone, Aripiprazole, Seroquel) with no major dose changes for at least 4 weeks.
5. A minimum PANSS total score of 55 at screening and baseline and a score of at least 4 (moderate) on the subscale of the PANSS (suspiciousness/persecution) at screening.
6. Have a Clinical Global Impressions-Severity (CGI-S) scale score of at least 4 (moderately ill) at baseline.
7. Must be able to communicate effectively with the investigator and study coordinator and have the ability to provide informed consent.
8. Must be able to use nasal spray.
9. Must demonstrate an acceptable degree of compliance with medication and procedures in the opinion of the investigator.

Exclusion Criteria:

Subjects will be excluded from the study of they meet any of the following criteria:

1. Are pregnant or are breastfeeding (negative pregnancy test at screening).
2. A urine drug screen performed at screening must not show evidence of recent use of drugs of abuse.
3. Any active medical condition that in the opinion of the investigator will interfere with the objectives of the study.
4. Are unsuitable in any way to participate in this study, in the opinion of the investigator.
5. Another current DSM-IV diagnosis other than Schizophrenia.

Permitted:

Subjects on one SSRI, and/or sleep medication (diphenhydramine, zolpidem, zaleplon, or diazepam), at a reasonable dose, as judged by the investigator, is permitted in this study.

Primary outcomes:
measure: Total Score in the Positive and Negative Syndrome Scale (PANSS)
timeFrame: performed at each visit (weekly)
Secondary outcomes:
measure: Clinical Global Impression-Severity of Illness
timeFrame: performed at each visit (weekly)
measure: Calgary Depression Scale for Schizophrenia
timeFrame: performed at each visit (weekly)
measure: Clinical Global Impression-Global Improvement
timeFrame: Performed at Visits 2-8 (weekly)
measure: Global Assessment of Functioning
timeFrame: performed at each visit (weekly)
measure: Hamilton Anxiety Scale
timeFrame: performed at each visit (weekly)
measure: Peabody Picture Vocabulary Test
timeFrame: Visit 1 only
measure: Letter Number Sequencing Memory Test
timeFrame: Visits 1, 4, and 8 (every 4 weeks)
measure: Reading Trust in the Eyes Test (RTET)
timeFrame: Visits 1, 4, 5 and 8 (every 4 weeks)
measure: California Verbal Learning Test-Second Edition
timeFrame: Visits 1, 4, and 8 (every 4 weeks)
measure: Profile of Mood States
timeFrame: Visits 1 and 5 (first visit and 5 weeks later)
measure: Paranoid Thought Scale
timeFrame: Visits 1-8 (weekly)
measure: Arizona Sexual Experience Scale (ASEX)
timeFrame: Visits 1-8 (weekly)
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California San Diego
state: California
Study officials:
affiliation: University of California, San Diego
name: David Feifel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Feifel D, Macdonald K, Cobb P, Minassian A. Adjunctive intranasal oxytocin improves verbal memory in people with schizophrenia. Schizophr Res. 2012 Aug;139(1-3):207-10. doi: 10.1016/j.schres.2012.05.018. Epub 2012 Jun 8.
citation: Feifel D, Macdonald K, Nguyen A, Cobb P, Warlan H, Galangue B, Minassian A, Becker O, Cooper J, Perry W, Lefebvre M, Gonzales J, Hadley A. Adjunctive intranasal oxytocin reduces symptoms in schizophrenia patients. Biol Psychiatry. 2010 Oct 1;68(7):678-80. doi: 10.1016/j.biopsych.2010.04.039. Epub 2010 Jul 7.