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Oxytocin as Adjunctive Therapy for Schizophrenia

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by IRCCS Centro San Giovanni di Dio Fatebenefratelli
Sponsor:
Information provided by (Responsible Party):
IRCCS Centro San Giovanni di Dio Fatebenefratelli
ClinicalTrials.gov Identifier:
NCT01699997
First received: October 2, 2012
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: Oxytocin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Use of Oxytocin as Adjunctive Therapy for the Treatment of Schizophrenia: a Randomized, Double Blind Trial

Resource links provided by NLM:


Further study details as provided by IRCCS Centro San Giovanni di Dio Fatebenefratelli:

Primary Outcome Measures:
  • Change in PANSS negative score, as measured at T0 and at 2,4,6 and 8 months. [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Using the PANSS negative score as primary end-point, the investigators expect to observe a reduction in PANSS negative subscale scores in the treated group ranging from 0.9 to 2, with an effect size Cohens d=0.45, in agreement with the results of a previous study, in which authors who observed a reduction of 1.7 with an effect size Cohens d= 0.5. The investigators also expect that OXT will have a positive influence on the patients quality of life and reduction of PANSS positive subscale score. Correlations between OXT plasma levels, symptoms, and response to treatment will be evaluated to identify respondent and non-respondent patient groups


Secondary Outcome Measures:
  • PANSS total score change. [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    The secondary end-point will be the PANSS total score


Other Outcome Measures:
  • Brief Assessment of Cognitive deficits in Schizophrenics (BACS) score change [ Time Frame: 8 months ] [ Designated as safety issue: No ]
  • Reading the Mind in the Eyes Test (RMET) score change. [ Time Frame: 8 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: January 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oxytocin
Each treatment will consist of 10 insufflations (5/nostril alternating between nostrils) of OXT Spray, which contains approximately 40 international units (IU) of OXT
Drug: Oxytocin
Intranasal spray with 40 IU of OXT
Placebo Comparator: Placebo vial
Each treatment will consist of 10 insufflations (5/nostril alternating between nostrils) of placebo Spray, which contains all OXT Spray ingredients except for oxytocin.
Drug: Placebo
Intranasal spray with placebo solution

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

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01699997

Contacts
Contact: Giovanni de Girolamo, M.D. 0039-0303501590 gdegirolamo@fatebenefratelli.it
Contact: Jessica Dagani, Clin. Psych. 0039-0303501333 jdagani@fatebenefratelli.it

Locations
Italy
Statistical Unit, Institute of Biomathematics, University of Urbino Active, not recruiting
Urbino, Pesaro Urbino, Italy
IRCCS Fatebenefratelli Recruiting
Brescia, Italy, 25125
Contact: Giovanni de Girolamo, M.D.    0039-0303501590    gdegirolamo@fatebenefratelli.it   
Principal Investigator: Giovanni de Girolamo, M.D.         
Department of Mental Health Recruiting
Desenzano, Italy, 25024
Contact: Francesco Saviotti, M.D.    0039-0309037395    francescomaria.saviotti@aod.it   
Principal Investigator: Francesco Saviotti, M.D.         
Institute of Neuroscience, National Research Council Active, not recruiting
Milan, Italy, 20129
Programma 2000, Department of Mental Health Recruiting
Milan, Italy, 20158
Contact: Emiliano Monzani, M.D.    0039-02 66809801    emiliano.monzani@gmail.com   
Principal Investigator: Emiliano Monzani, M.D.         
Department of Mental Health Recruiting
Padua, Italy, 35124
Contact: Paolo Scocco, M.D.    0039-0498217070    scocco.paolo@virgilio.it   
Principal Investigator: Paolo Scocco, M.D.         
Psychiatric Clinic, University of Pisa Recruiting
Pisa, Italy, 56100
Contact: Stefano Pini, M.D.    0039-0502219780    stefano.pini@med.unipi.it   
Principal Investigator: Stefano Pini, M.D.         
Psychiatric Clinic, University of Udine Recruiting
Udine, Italy, 33100
Contact: Matteo Balestrieri, M.D.    0039-0432559627    matteo.balestrieri@uniud.it   
Principal Investigator: Matteo Balestrieri, M.D.         
Sponsors and Collaborators
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Investigators
Principal Investigator: Giovanni de Girolamo, M.D. IRCCS Fatebenefratelli, Brescia
  More Information

Additional Information:
No publications provided

Responsible Party: IRCCS Centro San Giovanni di Dio Fatebenefratelli
ClinicalTrials.gov Identifier: NCT01699997     History of Changes
Other Study ID Numbers: RF-2010-2311148
Study First Received: October 2, 2012
Last Updated: March 3, 2014
Health Authority: Italy: Ministry of Health

Keywords provided by IRCCS Centro San Giovanni di Dio Fatebenefratelli:
Schizophrenia
Oxytocin
RCT

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Oxytocin
Oxytocics
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014