Clinical trial NCT06136390: OXYMIND: Oxytocin-augmented Group Psychotherapy for Patients With Schizophrenia
Official title: OXYMIND: Oxytocin-augmented Group Psychotherapy for Patients With Schizophrenia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Schizophrenia Spectrum Disorders
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2023-11-18
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 a lower NS by OXT administration in the positive social context of MBGT in SSD. The investigators also demonstrated that NS and other symptoms improved after mindfulness-based group psychotherapy (MBGT). The aim of this study in individuals with SSD is to examine the effect of combining OXT administration with MBGT on NS, affect, and stress with psychological and biological markers. 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. 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 MBGT in SSD. The investigators also demonstrated that NS and other symptoms improved after mindfulness-based group psychotherapy (MBGT).

The aim of this study in individuals with SSD is to examine the effect of combining OXT administration with MBGT on NS, affect, and stress. 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 T7 - T0 of the negative syndrome subscale of the PANSS (Positive and Negative Syndrome Scale) after 4 weeks. The PANSS as a validated and structured clinical interview will be collected by a blinded psychiatrist. MBGT - sessions by experienced psychotherapists take place over four weeks. These sessions as a positive social context take place once a week in a group of about six patients. Participants received 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.

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 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

Primary outcomes:
measure: Change in PANSS Negative Symptoms
timeFrame: Baseline (T0), post-intervention at week 4 (T4) and follow-up (week 8, T5)
Secondary outcomes:
measure: Change and group differences in BNSS Brief Negative Symptom Scale
timeFrame: Baseline (T0), post-intervention at week 4 (T7) and follow-up (week 8, T8)
measure: Change and group differences in SNS Negative Symptoms
timeFrame: Baseline (T0), post-intervention at week 2 (T3), post-intervention at week 4 (T9) and follow-up (week 8, T5)
measure: Change and group differences in CDSS Calgary Depression Scale of Schizophrenia
timeFrame: Baseline (T0), post-intervention at week 4 (T7) and follow-up (week 8, T8)
measure: Change and group differences in cortisol saliva levels
timeFrame: Baseline (T0), pre- and post-intervention in week 1 - 4 (T1-T7) and follow-up (week 8, T5)
measure: Change and group differences in DASS-21 Depression, Anxiety, and Stress Scale
timeFrame: aseline (T0), post-intervention at week 2 (T3), post-intervention at week 4 (T7) and follow-up (week 8, T9)
measure: Change and group differences in stress via visual analogue scale (Bubbles)
timeFrame: Baseline (T0), pre- and post-intervention in week 1 - 4 (T1-T7) and follow-up (week 8, T8)
measure: Change and group differences in PANAS (Positive and Negative Affect Scale)
timeFrame: Baseline (T0), pre- and post-intervention in week 1 - 4 (T1-T7) and follow-up (week 8, T8)
measure: Change and group differences in PSP Social Functioning
timeFrame: Baseline (T0), post-intervention at week 4 (T7) and follow-up (week 8, T8)
measure: Change and group differences in SMQ Mindfulness
timeFrame: Baseline (T0), post-intervention at week 4 (T7) and follow-up (week 8, T8)
measure: Change and group differences in GCQ-S Group Climate Questionnaire (Short Version)
timeFrame: Post-intervention at week 1-4 (T1-T7)
measure: Change and group differences in endocannibinoid levels
timeFrame: Baseline (T0), post-intervention week 1 (T1), post-intervention week 4 (T7) and follow-up (week 8, T8)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin, Campus Benjamin Franklin
Study officials:
affiliation: Charite University, Berlin, Germany
name: Marco Zierhut, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Charite University, Berlin, Germany
name: Kerem Böge, PD
role: PRINCIPAL_INVESTIGATOR
affiliation: Charite University, Berlin, Germany
name: Eric Hahn, PD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.