SchizophreniaPhase 2NCT01699997
Oxytocin as Adjunctive Therapy for Schizophrenia
A Phase 2 study testing Oxytocin in people with Schizophrenia, run by IRCCS Centro San Giovanni di Dio Fatebenefratelli at 7 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Oxytocin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 7 sitesItaly
- Study dates
- Jan 2014to Nov 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Italy7 sites
IRCCS Fatebenefratelli
Brescia, 25125
Department of Mental Health
Desenzano, 25024
Institute of Neuroscience, National Research Council
Milan, 20129
Department of Mental Health
Padua, 35124
Psychiatric Clinic, University of Pisa
Pisa, 56100
Psychiatric Clinic, University of Udine
Udine, 33100
Statistical Unit, Institute of Biomathematics, University of Urbino
Urbino, Pesaro Urbino
About this study
Official title: The Use of Oxytocin as Adjunctive Therapy for the Treatment of Schizophrenia: a Randomized, Double Blind Trial
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:
Read more
- To assess the efficacy of intranasal OXT in reducing negative symptoms in patients with schizophrenia in association with second-generation antipsychotics (SGA);
- 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.
Read the detailed description
The project has two main aims:
- 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.
- 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.
- Conditions
- Schizophrenia
- Being tested
- Oxytocin, Placebo
- Keywords
- Schizophrenia, Oxytocin, RCT
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxytocinDrug
Intranasal spray with 40 IU of OXT
PlaceboDrug
Intranasal spray with placebo solution
| Study group | Role | What they receive |
|---|---|---|
| Oxytocin | Experimental | Each treatment will consist of 10 insufflations (5/nostril alternating between nostrils) of OXT Spray, which contains approximately 40 international units (IU) of OXT Receives: Drug: Oxytocin |
| Placebo vial | Placebo comparator | Each treatment will consist of 10 insufflations (5/nostril alternating between nostrils) of placebo Spray, which contains all OXT Spray ingredients except for oxytocin. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in PANSS negative score, as measured at T0 and at 2,4,6 and 8 months.
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
Measured: 8 months
Secondary outcomes (1)
PANSS total score change.
The secondary end-point will be the PANSS total score
Measured: 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2012 (estimated)
- Study startJan 2014
- Primary completionApr 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS Centro San Giovanni di Dio Fatebenefratelli
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giovanni de Girolamo, M.D., IRCCS Centro San Giovanni di Dio Fatebenefratelli
- Investigators
- Giovanni de Girolamo, M.D., Principal investigator, IRCCS Fatebenefratelli, Brescia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01699997
- Sponsor's protocol ID
- RF-2010-2311148
- Status last verified
- Feb 2016
- First submitted
- 2 Oct 2012
- Last updated
- 24 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 26883950Lee 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.
PubMed 26879587
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Oxytocin as Adjunctive Therapy for the Treatment of Schizophrenia: a Randomized, Double Blind Trial
- ClinicalTrials.gov ID
- NCT01699997
- Acronym / sponsor ID
- RF-2010-2311148
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, Oxytocin, RCT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- IRCCS Centro San Giovanni di Dio FatebenefratelliUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- Apr 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 4 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To assess the efficacy of intranasal OXT in reducing negative symptoms in patients with schizophrenia in association with second-generation antipsychotics (SGA);
- 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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oxytocin | Experimental | Drug: OxytocinEach treatment will consist of 10 insufflations (5/nostril alternating between nostrils) of OXT Spray, which contains approximately 40 international units (IU) of OXT |
| Placebo vial | Placebo comparator | Drug: PlaceboEach treatment will consist of 10 insufflations (5/nostril alternating between nostrils) of placebo Spray, which contains all OXT Spray ingredients except for oxytocin. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OxytocinIntranasal spray with 40 IU of OXT | Drug | Oxytocin |
| PlaceboIntranasal spray with placebo solution | Drug | Placebo vial |
Primary outcome
Change in PANSS negative score, as measured at T0 and at 2,4,6 and 8 months.
Time frame: 8 months
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
1 secondary outcome
PANSS total score change.
Time frame: 8 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2016.
- Derived from this study: PubMed 26883950Dagani 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.
- Derived from this study: PubMed 26879587Lee 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.
- This is the website of the Coordinating CentreLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giovanni de Girolamo, M.D. principal investigator
IRCCS Fatebenefratelli, Brescia
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oxytocin in people with Schizophrenia, run by IRCCS Centro San Giovanni di Dio Fatebenefratelli at 7 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in PANSS negative score, as measured at T0 and at 2,4,6 and 8 months. (time frame: 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01699997, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2016.