Oxytocin-augmented Cognitive-behavioral Group-based Short-term Intervention for Loneliness

Loneliness Clinical Trial

Official title:

Effects of an Oxytocin-augmented Cognitive-behavioral Group-based Short-term Intervention on Neural and Behavioral Correlates of Loneliness

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04137432
• Other study ID #: GIF2
• Status: Enrolling by invitation
• Phase: Phase 1
• Start date: September 26, 2019
• Est. completion date: December 2020

Study information

• Verified date: October 2019
• Source: University Hospital, Bonn
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the clinical potential of oxytocin (OT) as an adjunct to a cognitive-behavioral group-based shortterm intervention for participants suffering from loneliness.

Description:

Loneliness has a high prevalence in Western societies and poses a significant health problem. Among its many implications, loneliness has been associated with increased risk for coronary heart disease and stroke, depression, cognitive decline, dementia, and mortality. At the neural level, several networks may be involved in loneliness, including the reward circuitry, which mediates social reward, and the amygdala, which signals social threat. Intranasal OT has been reported to regulate activity in both the reward system and the amygdala. Therefore, it may serve as an adjunct to a cognitive-behavioral short-term intervention for high lonely participants.

In this randomized, double-blind, placebo-controlled design study, effects of intranasal OT (24 international units (UI)) as a pharmacological augmentation given before the start of four sessions of a cognitive-behavioral short-term intervention in groups of six to eight participants (based on established interpersonal psychotherapy modules to reduce loneliness) will be investigated. Healthy, but high lonely participants will complete functional magnetic resonance imaging (fMRI) tasks in a separate testing session before the start of the intervention (testing session 1). In the first session of the intervention, the psychotherapist will inform the participants about the procedure of the intervention and participants will get to know the other participants in their intervention group (testing session 2). In the next four sessions (testing sessions 3-6), participants will receive 24 IU of intranasal OT 30 minutes before the start of the intervention. Sessions of the intervention will be conducted weekly. After completion of the intervention, participants will again undergo fMRI scanning (testing session 7). Three weeks and three months after completion of the intervention, follow-up measurements of the experienced loneliness and subjective well-being will be collected.

All fMRI testing sessions (1 and 7) will include following tasks:

1. Blood-oxygen-level dependent (BOLD) signal will be measured while participants play a single-round trust game in the role of an investor. Participants will have to decide the amount of money they want to invest in an unknown trustee without receiving feedback about the decisions of the trustees. If the participant chooses to invest, that amount will be tripled and added to the trustee's account. The trustee may keep all of the money for him/herself or share the money with the investor. Participants will be informed of the collection of the trustee's decisions in a previous study for all possible investments. Furthermore, participants will view an image of a randomly chosen trustee from the previous study during the MRI session. In a control condition, participants will play a risk game and invest money in a computer (which will randomly decide whether the money will be shared).

2. BOLD signal will be assessed while participants undergo a social touch task. Trials will include slow (~ 5 cm/s) and fast touch (~ 20 cm/s) across 20 cm of the shins as well as a control condition (no touch). The touch will be administered by an experimenter that cannot be seen by the participants. After each trial, participants will be asked to rate the perceived comfort of the stimulation.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 60
• Est. completion date: December 2020
• Est. primary completion date: September 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• UCLA loneliness scale score equal to or greater than 55

Exclusion Criteria:

• current psychiatric illness

• current psychiatric medication or psychotherapy

• MRI contraindication (e.g. metal in body, claustrophobia)

• pregnancy

Related Conditions & MeSH terms

• Loneliness

Intervention

Drug:
• Oxytocin nasal spray
Intranasal administration of 24 international units oxytocin.
• Placebo
The placebo nasal sprays contains identical ingredients except for the peptide itself.

Locations

Country	Name	City	State
Germany	Department of Psychiatry, University of Bonn	Bonn

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Bonn	Prof. Simone Shamay-Tsoory, University of Haifa, The German-Israeli Foundation for Scientific Research and Development

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Oxytocin plasma concentrations	Oxytocin plasma concentrations will be assessed in testing sessions 1 and 7 before the fMRI scans will be conducted.	Five to seven weeks (before the start and after the completion of the intervention)
Primary	Scores on the UCLA Loneliness Scale	Loneliness, as measured via the University of California, Los Angeles (UCLA) loneliness scale before the start (testing session 1) and after completion of the intervention (testing session 7) (+ follow-up measurements 3 weeks and 3 months after completion of the intervention), will be analyzed using mixed ANOVAs with the software SPSS and Bonferroni-corrected post-hoc t-tests.	Five to seven weeks (+ Follow-Up measurements 3 weeks and 3 months after completion of the intervention)
Primary	State loneliness (numeric rating scale)	State loneliness will be measured on a numeric rating scale ranging from 1 to 100 at the start and the end of each testing session and analyzed using mixed ANOVAs in SPSS and Bonferroni-corrected post-hoc t-tests.	Five to seven weeks (+ Follow-Up measurements 3 weeks and 3 months after completion of the intervention)
Primary	Scores on the World Health Organization (WHO) Five Well-Being Index	Psychological well-being will be assessed using the World Health Organization (WHO) Five Well-Being Index before each testing session and analyzed using mixed ANOVAs in SPSS and Bonferroni-corrected post-hoc t-tests.	Five to seven weeks (+ Follow-Up measurements 3 weeks and 3 months after completion of the intervention)
Primary	Scores on the Perceived Stress Scale	Perceived stress will be assessed using the Perceived Stress Scale (PSS-10) before each testing session and analyzed using mixed ANOVAs in SPSS and Bonferroni-corrected post-hoc t-tests.	Five to seven weeks (+ Follow-Up measurements 3 weeks and 3 months after completion of the intervention)
Primary	Neural responses in the trust game	The BOLD signal as response to the trust game will be compared to the risk game and changes in the signal from testing session 1 to 7 will be compared between the OT and PLC groups. Results from both fMRI testing sessions will be compared to a non-lonely healthy control group (data were collected in a previous study with the same fMRI tasks in two fMRI sessions five to seven weeks apart from each other). Analyses will focus on anatomically defined regions of interests (ROIs) associated with trust (insula, amygdala, nucleus accumbens, and ventromedial prefrontal cortex). For analyses of fMRI data, standard procedures of the software SPM12 will be used. The family-wise error rate will be used to correct p-values for multiple comparisons and p < .05 will be considered significant. fMRI data will be correlated with behavioral data of the trust game and the UCLA Loneliness scores.	Five to seven weeks (fMRI task will be completed before the start and after the completion of the intervention and will take about 15 minutes)
Primary	Amount of invested money in the trust game as an economic value of trust	Behavioral data of the trust game (invested money) will be analyzed using mixed ANOVAs in SPSS and compared between the OT and PLC groups. Post-hoc t-tests will be Bonferroni-corrected. Behavioral data will be correlated with fMRI data of the trust game and the UCLA Loneliness scores.	Five to seven weeks (fMRI task will be completed before the start and after the completion of the intervention and will take about 15 minutes)
Primary	Neural responses to interpersonal touch	BOLD signals of slow touch trials will be contrasted with fast touch trials. Again, results of the OT group will be compared with the PLC group and results of lonely participants will be compared to the results of a non-lonely healthy control group. Analyses will focus on ROIs associated with the processing of social touch (amygdala, hippocampus, insula, and primary somatosensory cortex). For analyses of fMRI data, standard procedures of SPM12 will be used (preprocessing & a two-stage approach based on the general linear model for statistical analyses). The family-wise error rate will be used to correct p-values for multiple comparisons and p < .05 will be considered significant. Post-hoc t-tests will be Bonferroni-corrected. fMRI data will be correlated with behavioral data of the touch task and the UCLA loneliness scores.	Five to seven weeks (fMRI task will be completed before the start and after the completion of the intervention and will take about 15 minutes)
Primary	Comfort ratings of interpersonal touch in the fMRI task (visual analogue scale)	Behavioral data of the fMRI interpersonal touch task (comfort ratings on a visual analogue scale) will be analyzed using mixed ANOVAs in SPSS and compared between the OT and the PLC group. Post-hoc t-tests will be Bonferroni-corrected. Comfort ratings will be correlated with fMRI data of the interpersonal touch task and the UCLA loneliness scores.	Five to seven weeks (fMRI task will be completed before the start and after the completion of the intervention and will take about 15 minutes)
Primary	Therapeutic relationship (positive bonding) measured by the Group Questionnaire (GQ-D)	The therapeutic relationship (positive bonding) will be measured after all intervention sessions using the Group Questionnaire (GQ-D; subscale Positive Bonding). OT effects will be analyzed by conducting mixed ANOVAs and Bonferroni-corrected post-hoc t-tests in SPSS.	Five weeks
Primary	Therapeutic relationship (positive working) measured by the Group Questionnaire (GQ-D)	The therapeutic relationship (positive working) will be measured after all intervention sessions using the GQ-D (subscale Positive Working). OT effects will be analyzed by conducting mixed ANOVAs and Bonferroni-corrected post-hoc t-tests in SPSS.	Five weeks
Primary	Therapeutic relationship (negative relationship) measured by the Group Questionnaire (GQ-D)	The therapeutic relationship (negative relationship) will be measured after all intervention sessions using the GQ-D (subscale Negative Relationship). OT effects will be analyzed by conducting mixed ANOVAs and Bonferroni-corrected post-hoc t-tests in SPSS.	Five weeks
Secondary	Interpersonal distance	Interpersonal distance will be assessed by an adapted version of an established stop-distance paradigm. Participants start from a distance of ~ 2 m and move towards the investigator until their ideal distance is reached (trials 1 and 3) or until they feel slightly uncomfortable (trials 2 and 4). The task will be applied by the same investigator at testing sessions 1 and 7. Data will be analyzed using mixed ANOVAs and Bonferroni-corrected t-tests in SPSS to compare treatment group as well as lonely participants and non-lonely controls.	Five to seven weeks (before the start and after the completion of the intervention)
Secondary	Neural activity at resting state	fMRI will be performed to measure BOLD-signal while participants lay in the MRI-scanner with eyes open. Participants will be instructed to look at a fixation cross for ~ 6 minutes. Functional connectivity will be analyzed using default preprocessing parameters implemented in the CONN-toolbox. Changes in functional connectivity will be contrasted between treatment groups and activity will be compared to those of non-lonely controls.	Five to seven weeks (fMRI task will be completed before start and after completion of the intervention and will take about 6 minutes)

External Links

•   Neuromodulation of Emotion (NEMO) research group