Oxytocin-Augmented Group Psychotherapy for Patients With Schizophrenia - an Oxytocin-dose Comparison

NCT ID: NCT07265180

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-08
• Study Completion Date: 2026-11-30

Brief Summary

The effectiveness of current treatment options for sociocognitive deficits and negative symptoms (NS) in schizophrenia spectrum disorders (SSD) remains limited. The cause of NS is thought to be an interference between the mesocorticolimbic dopamine system for social reward expectancy and the network for socioemotional processes. Oxytocin (OXT) may enhance functional connectivity between these neuronal networks. Lower plasma OXT levels correlate negatively with NS severity and deficits in social cognition in SSD. It has been shown that intranasal OXT administration improves social cognition in healthy subjects but in SSD results are inconsistent. According to the social salience hypothesis, the effect of OXT varies depending on the social context and individual factors. Also, OXT-mediated effects on psychopathology and NS may depend on genetic variants of OXT receptors (OXTR). In a pilot study, the investigators demonstrated lower NS by OXT administration in a positive social context of mindfulness-based group psychotherapy (MBGT) in SSD. The investigators also demonstrated that symptoms improved after MBGT. A more recent study suggests that, compared to placebo, administering OXT in a positive social context via MBGT leads to significant between-group differences favoring OXT, particularly in NS, affect, and stress. Building on these findings, the present study investigates the stability of these effects, along with psychological and biological markers, in a larger sample of individuals with SSD. The main hypothesis to be tested is that the use of OXT compared to placebo prior to MBGT in patients with SSD will result in a greater reduction in NS with a higher OXT dosage. The research design is based on an experimental, triple-blind, randomized, placebo-controlled trial.

Detailed Description

Schizophrenia spectrum disorders (SCZ) are severe mental illnesses with a lifetime prevalence of 1-2%. Three core syndromes characterize SCZ: positive and negative syndromes (NS), as well as a cognitive syndrome. The effectiveness of current treatment options for negative symptoms (NS) and sociocognitive deficits in schizophrenia spectrum disorders (SSD) remains limited.

The cause of NS is thought to be an interference between the mesocorticolimbic dopamine system for social reward expectancy and the network for socioemotional processes. Oxytocin (OXT) may enhance functional connectivity between these neuronal networks. Lower plasma OXT levels correlate negatively with NS severity and deficits in social cognition in SSD. It has been shown that intranasal OXT administration improves social cognition in healthy subjects but in SSD results are inconsistent. According to the social salience hypothesis, the effect of OXT varies depending on the social context and individual factors. Also, OXT-mediated effects on psychopathology and NS may depend on genetic variants of OXT receptors (OXTR). In a pilot study, the investigators demonstrated lower NS by OXT administration in a positive social context of mindfulness-based group psychotherapy (MBGT) in SSD. The investigators also demonstrated that NS and other symptoms improved after MBGT. A more recent study suggests that, compared to placebo, administering OXT in a positive social context via MBGT leads to significant between-group differences favoring OXT, particularly in NS, affect, and stress. Building on these findings, the present study investigates the stability of these effects, along with psychological and biological markers, in a larger sample of individuals with SSD. The main hypothesis to be tested is that the use of OXT compared to placebo prior to MBGT in patients with SSD will result in a greater reduction in NS, i.e. the difference in T0-T8 of the total score on the BNSS (Brief Negative Symptom Scale) after 4 weeks. The BNSS as a validated rater-based instrument designed for clinical trials will be collected by a blinded psychiatrist. MBGT-sessions by experienced psychotherapists take place once a week over four weeks in a group of six patients. They serve as a positive social context for OXT administration. Participants receive either synthetic oxytocin or a placebo 30 minutes before MBGT.

The role of genetic variations (OXTR genes) for the treatment effect on NS will be explored too as well as the effect on various stress markers including cortisol levels and the endocannabinoid system, affect, group cohesion and mindfulness.

The research design is based on an experimental, triple-blind, randomized, placebo-controlled trial.

Conditions

Schizophrenia Spectrum Disorders (SSD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Oxytocin (24 I.U. Syntocinon®)

The patients received a spray of synthetic oxytocin (24 I.U. Syntocinon®) in combination with mindfulness-based group therapy (MBGT) over 4 weeks once a week. Due to an effect latency of 30-80 min after intranasal administration of oxytocin on social behavior, the dose was administered 30 min before the 50 min session.

Group Type: ACTIVE_COMPARATOR

Oxytocin

Intervention Type: OTHER

Oxytocin nasal spray in combination with mindfulness based group therapy (MBGT).

Oxytocin (48 I.U. Syntocinon®)

The patients received a spray of synthetic oxytocin (48 I.U. Syntocinon®) in combination with mindfulness-based group therapy (MBGT) over 4 weeks once a week. Due to an effect latency of 30-80 min after intranasal administration of oxytocin on social behavior, the dose was administered 30 min before the 50 min session.

Group Type: ACTIVE_COMPARATOR

Oxytocin

Intervention Type: OTHER

Oxytocin nasal spray in combination with mindfulness based group therapy (MBGT).

Placebo

The patients received a placebo nasal spray in combination with mindfulness-based group therapy (MBGT) over 4 weeks once a week. Due to an effect latency of 30-80 min after intranasal administration of oxytocin on social behavior, the dose was administered 30 min before the 50 min session.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo nasal spray in combination with mindfulness based group therapy (MBGT).

Interventions

Oxytocin

Oxytocin nasal spray in combination with mindfulness based group therapy (MBGT).

Intervention Type: OTHER

Placebo

Placebo nasal spray in combination with mindfulness based group therapy (MBGT).

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Declaration of consent
• Psychiatric diagnosis of schizophrenia (ICD-10: F2x.x spectrum) for group of patients
• Mild to moderate positive symptoms (5 ≤ Positive symptoms on individual items using P-PANSS)
• German should either be the native language or spoken at a native level
• No change in systematically recorded psychopharmacological medication in the last 2 weeks before study inclusion

Exclusion Criteria

• Acute psychotic episode with severe positive symptoms (ICD-10: F2 spectrum, 6 ≥ positive symptoms on individual items using P-PANSS)
• Acute suicidality
• Acute consumption phase of a substance dependence, except nicotine
• No severe physical impairments, neurological diseases and e.g. severe craniocerebral trauma e.g. early childhood brain damage
• Pregnancy and breastfeeding
• Current acute electroconvulsive therapy

If one of the following criteria applies to the participants, we will conduct an individual consultation in advance to determine whether participation in the study is possible:

• Overweight or underweight (body mass index (BMI) < 17.5 or > 30)
• Disease of the endocrine system
• Impaired kidney or liver function
• Metabolic diseases
• Asthma
• Change in blood potassium or sodium levels

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

Kerem Böge

Prof. Dr. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marco Zierhut, MD

Role: PRINCIPAL_INVESTIGATOR

Charite University, Berlin, Germany

Kerem Böge, Prof.

Role: PRINCIPAL_INVESTIGATOR

Charite University, Berlin, Germany

Eric Hahn, PD

Role: PRINCIPAL_INVESTIGATOR

Charite University, Berlin, Germany

Locations

Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Campus Charité Mitte

Berlin, State of Berlin, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Marco Zierhut, MD

Role: CONTACT

marco.zierhut@charite.de

004930450517547

Kerem Böge, Prof.

Role: CONTACT

kerem.boege@charite.de

004930450517789

Facility Contacts

Marco Zierhut, MD

Role: primary

marco.zierhut@charite.de

004930450517547

Kerem Böge, Prof.

Role: backup

kerem.boege@charite.de

004930450517789

References

Boge K, Bergmann N, Zierhut M, Hahne I, Braun A, Kraft J, Conell I, Ta TMT, Thomas N, Chadwick P, Ripke S, Hahn E. The relationship between mindfulness and empathy with the oxytocinergic system in persons with schizophrenia spectrum disorders - A proof-of-concept randomized controlled trial (OXYGEN). Int J Clin Health Psychol. 2024 Jul-Sep;24(3):100503. doi: 10.1016/j.ijchp.2024.100503. Epub 2024 Sep 10.

Reference Type: BACKGROUND

PMID: 39308779 (View on PubMed)

Zierhut M, Bergmann N, Hahne I, Wohlthan J, Kraft J, Braun A, Tam Ta TM, Hellmann-Regen J, Ripke S, Bajbouj M, Hahn E, Boge K. The combination of oxytocin and mindfulness-based group therapy for empathy and negative symptoms in schizophrenia spectrum disorders - A double-blinded, randomized, placebo-controlled pilot study. J Psychiatr Res. 2024 Mar;171:222-229. doi: 10.1016/j.jpsychires.2024.01.014. Epub 2024 Jan 9.

Reference Type: BACKGROUND

PMID: 38309212 (View on PubMed)

Boge K, Hahne I, Bergmann N, Wingenfeld K, Zierhut M, Thomas N, Ta TMT, Bajbouj M, Hahn E. Mindfulness-based group therapy for in-patients with schizophrenia spectrum disorders - Feasibility, acceptability, and preliminary outcomes of a rater-blinded randomized controlled trial. Schizophr Res. 2021 Feb;228:134-144. doi: 10.1016/j.schres.2020.12.008. Epub 2021 Jan 9.

Reference Type: BACKGROUND

PMID: 33434727 (View on PubMed)

Other Identifiers

OXYMIND2.0

Identifier Type: -

Identifier Source: org_study_id