Oxytocin as Adjunctive Therapy for Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Oxytocin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Intranasal spray with 40 IU of OXT; Intranasal spray with placebo solution
Intervention MeSH terms: Oxytocin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Schizophrenia; Oxytocin; RCT