Clinical trial NCT01699997: Oxytocin as Adjunctive Therapy for Schizophrenia
Official title: The Use of Oxytocin as Adjunctive Therapy for the Treatment of Schizophrenia: a Randomized, Double Blind Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Keywords: Schizophrenia
Oxytocin
RCT
Lead sponsor: IRCCS Centro San Giovanni di Dio Fatebenefratelli
Sponsor class: OTHER
First posted: 2012-10-04
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Background: A large body of research has shown that Oxytocin (OXT) is an important prosocial peptide and there is also initial evidence that the central OXT system is altered in several mental disorders that are characterized by severe social disturbances and deficits, such as anxiety disorders with prominent social dysfunction (e.g., schizophrenia), mood disorders and borderline personality disorder. OXT may reduce psychotic symptoms and may diminish certain social cognition deficits that are not improved by current antipsychotic medications.

Aims: The project has two main aims, listed below:

1. To assess the efficacy of intranasal OXT in reducing negative symptoms in patients with schizophrenia in association with second-generation antipsychotics (SGA);
2. To use an Emotional Priming Paradigm task to assess pre- and post-treatment change in the patients general cognitive and emotional status.

Study Design: Randomized, double-blind, placebo-controlled, cross over design. Materials and methods: Patients involved in the study will be recruited in six centres in the north of Italy. Each subject (aged 18-45, with a duration of the disorder no longer than 10 years) will be enrolled after a screening phase. 80 patients will be randomly assigned to either 40 IU OXT once daily or vehicle placebo, in addition to their pre-study antipsychotic medication regimen: all reasonable attempts maintain the same SGA dosages throughout the study will be made. The study ratio is 1:1. The total study duration for each individual subject will be approximately 8 months, which includes an up to 7-day screening period, a baseline randomization visit, and a four month long cross-over treatment period. Subjects will be trained by researchers about the self-administration of intranasal OXT. A trustworthy caregiver will be trained as well. Each patient will receive every morning a SMS text message on his mobile phone as a reminder for OXT administration.

Before starting the treatment, all patients will be assessed with standardized assessment instruments and will undergo an in depth neuropsychological assessment; additional evaluations, including safety evaluations, will be performed at 4 and 8 month follow-ups.

The primary outcome measure will be the negative score in the Positive and Negative Syndrome Scale (PANSS) performed at 2,4,6 and 8 months since the start of the treatment.

Detailed description: The project has two main aims:

1. Aims of the cross-over study To assess the efficacy of intranasal OXT in reducing negative symptoms in patients with SZ (as evaluated with PANSS), in association with standard Second Generation Antipsychotics (SGA)treatment; recruited patients will be aged 18-45 years and will have a disorder duration of no longer than 10 years.
2. Aims of the neuropsychological assessment To use an Emotional Priming Paradigm (EPP) task to assess pre- and post-treatment change in the patients general cognitive and emotional status.

The investigators aim at treating a large sample size of patients with schizophrenia, consisting exclusively of patients with a limited disorder duration and rather young age, for a sufficiently long period of time. Our rationale for employing a longer treatment period than used in previous and on-going trials is to ascertain the possibility of a positive OXT dose-response relationship, which would be observable, however, with longer treatment exposure. Moreover, only patients with a disorder onset of 10 years or less will be enrolled.

They will then be standardized in terms of AP treatment and randomized to OXT or placebo for 8 months.

OXT is a hormone that is naturally present in the human body, and recent studies have suggested that patients with SZ show low levels of this neuropeptide. It is therefore hypothesized that the treatment proposed in this project might balance apparently lower OXT levels in these patients.

Finally, another innovative aspect of this project is the attention at ameliorating patients adherence to treatment by supporting them with a reminder program (automatic SMS will be sent every morning to remind patients the daily OXT self-administration) and involving a trustworthy caregiver who will be trained in OXT administration and will be asked to monitor the patient compliance by recording each self-administration on a written form.

Eligibility criteria: Inclusion Criteria:

* Patients with a diagnosis of SZ, according to DSM-IV criteria, for at least one year, evaluated with SCID/P
* A minimum PANSS total score of 55 (indicating moderate severity, due to ongoing AP treatment) .
* A minimum CGI-S score of 4
* Age between 18 and 45 years
* A disorder duration of no longer than 10 years
* Women of childbearing age must test negative for pregnancy at the time of enrolment.

All patients must:

* be on a therapeutic dose of a SGA (or a maximum 2 SGAs) with no major dose changes for at least 4 weeks.
* have the ability to provide informed consent
* be able to use a nasal spray
* reside in the service catchment area
* show evidence of no alcohol or substance dependence in the last year

Exclusion Criteria:

* Diagnosis of mental retardation
* Diagnosis of organic mental disorder
* History of no response to treatment with clozapine
* History of hypersensitivity to OXT or vehicle
* Alcohol or substance dependence in the last year
* Presence of, or history of clinically significant allergic rhinitis as assessed by the treating clinician
* Being pregnant or breastfeeding
* Having given birth in the past 6 months or breast-feeding in the past 3 months
* Low literacy as indicated by an inability to read and understand the consent form

Primary outcomes:
measure: Change in PANSS negative score, as measured at T0 and at 2,4,6 and 8 months.
timeFrame: 8 months
Secondary outcomes:
measure: PANSS total score change.
timeFrame: 8 months
Other outcomes:
measure: Brief Assessment of Cognitive deficits in Schizophrenics (BACS) score change
timeFrame: 8 months
measure: Reading the Mind in the Eyes Test (RMET) score change.
timeFrame: 8 months
Locations:
city: Urbino
country: Italy
facility: Statistical Unit, Institute of Biomathematics, University of Urbino
state: Pesaro Urbino
city: Brescia
country: Italy
facility: IRCCS Fatebenefratelli
city: Desenzano
country: Italy
facility: Department of Mental Health
city: Milan
country: Italy
facility: Institute of Neuroscience, National Research Council
city: Padua
country: Italy
facility: Department of Mental Health
city: Pisa
country: Italy
facility: Psychiatric Clinic, University of Pisa
city: Udine
country: Italy
facility: Psychiatric Clinic, University of Udine
Study officials:
affiliation: IRCCS Fatebenefratelli, Brescia
name: Giovanni de Girolamo, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dagani J, Sisti D, Abelli M, Di Paolo L, Pini S, Raimondi S, Rocchi MB, Saviotti FM, Scocco P, Totaro S, Balestrieri M, de Girolamo G. Do we need oxytocin to treat schizophrenia? A randomized clinical trial. Schizophr Res. 2016 Apr;172(1-3):158-64. doi: 10.1016/j.schres.2016.02.011. Epub 2016 Feb 14.
citation: Lee MR, Wehring HJ, McMahon RP, Liu F, Linthicum J, Verbalis JG, Buchanan RW, Strauss GP, Rubin LH, Kelly DL. Relationship of plasma oxytocin levels to baseline symptoms and symptom changes during three weeks of daily oxytocin administration in people with schizophrenia. Schizophr Res. 2016 Apr;172(1-3):165-8. doi: 10.1016/j.schres.2016.02.014. Epub 2016 Feb 12.