Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05432089 |
| Other study ID # |
0002-22-SHA |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
March 30, 2023 |
| Est. completion date |
July 1, 2025 |
Study information
| Verified date |
March 2023 |
| Source |
Shalvata Mental Health Center |
| Contact |
Omer Sedoff, Mrs. |
| Phone |
+972525708722 |
| Email |
omersedoff[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Introduction: Oxytocin (OT) is a nine-amino acid neuropeptide, known to have a fundamental
role in social communication. In a recent randomized, double-blind, placebo-controlled study
carried out in Shalvata Mental Health Center, OT was administrated to patients suffering from
severe mental health illness. The results indicated that OT has a clear beneficial effect on
therapeutic outcomes. However, to our knowledge, the effect of OT administration to both
patients and therapists on the therapeutic process was never tested. Substance administration
to caregivers is therefore possible, and could, in some cases, provide further knowledge
about the caregiving dynamics. Since we know the therapist's characteristics effect the
therapeutic alliance and that OT is associated with the therapeutic alliance,
patient-therapist bond, and therapy outcome, we are led to ask if OT administration to
patients and therapists could allow for a deeper understanding of OT's effects on the
therapeutic process.
Another variable found to be associated with the therapeutic process is Physiological
Synchronization. Physiological Synchronization (PS) is a primarily interpersonal phenomenon
which includes coordination of physiological signals between two or more interacting
individuals. Despite the rising number of studies examining PS, its physiological and
psychological mechanisms are yet to be fully understood. Based on literature indicating
associations between OT and PS, and associations each of them has with the therapeutic
process and its facilitators, in this study we wish to examine the influence of OT on PS
through intranasal OT administration to patients alone and to patients and therapists
together.
Research Hypotheses:
1. Patients receiving OT will demonstrate higher levels of PS during the measured session
compared to patients receiving placebo.
2. Patients receiving OT will report higher levels of perceived therapist empathy as
compared to patients receiving placebo.
3. These associations will be stronger when both patient and therapist receive OT in
comparison to patient alone.
4. Changed in PS and empathy will be associated with OT even after controlling for patient
rated alliance and session impact.
5. These findings will sustain after controlling for severity of symptoms and attachment
patterns.
Method:
Participants. Sixty patients and their therapists will be recruited for the pilot study.
Patients will be recruited from the inpatient adult psychiatric wards at Shalvata Mental
Health Center. Therapists in this study will be comprised of psychologists, psychiatrists,
and social workers, in different stages of seniority and training.
Instruments. Attachment patterns, symptom severity, side effects and therapeutic process
measurements - working alliance, perceived empathy and session impact - will be assessed
using self-report questionnaires. PS will be measured by recordings of the electrodermal
activity (EDA) measured by skin conductance signals, using a galvanic skin response (GSR)
device. Oxytocin Administration will be performed intranasally using a spray containing 24U.
Procedure. Sixty patients meeting inclusion criteria and their therapists will be recruited
for the pilot study. Dyads will be randomized and double-blindly allocated to receive
intra-nasal oxytocin or placebo. Dyads will be followed for two consecutive sessions,
approximately at their fourth and fifth sessions. After signing informed consent forms,
patients and therapists will complete therapeutic process measurements, and patients will be
assessed for the severity of their symptoms and attachment patterns. Prior to the first
session, patients will be administrated with either IN-OT or PLC and will wait for 30 minutes
before the beginning of the session. Skin conductance synchrony will be measured during the
session. At the end of the session, therapeutic process measurements will be assessed in both
patients and therapists, and patients will complete a side-effect questionnaire. Prior to the
second session, both patients and therapists will receive either IN-OT or PLC (each dyad will
receive the same substance) and will wait for 30 minutes before the beginning of the session.
Skin conductance synchrony will then be measured during the session. At the end of the
session, therapeutic process measurements will be assessed in both patients and therapists
alongside with a side-effect questionnaire.
The uniqueness of the proposed study is rooted in the view of the psychotherapy dyad as
undetached, by focusing on the dyad and not on the patient alone. Focusing on
patient-therapist synchronization lies on the understanding of the patient-therapist bond as
co-dependent and co-affected. Such research could increase our understanding of PS between
patient and therapist and its meaning in psychotherapy research and practice.
Description:
Oxytocin (OT) is a nine-amino acid neuropeptide, known to have a fundamental role in social
communication. Studies have shown that OT is involved in the attachment system in mammals and
in mother-infant bond. Furthermore, studies demonstrate that OT enhances the ability to trust
and improves the positive effects of social support during stress. In romantic relationships,
OT was found to increase positive communication during conflictual discourse between
partners, and was also found to be associated with different affiliative processes, such as
empathy, emotional regulation, pro-social behavior, and sense of belonging.
In a recent randomized, double-blind, placebo-controlled study carried out in Shalvata Mental
Health Center, OT was administrated to patients suffering from severe mental health illness.
The results indicated that OT has a clear beneficial effect on therapeutic outcomes. However,
to our knowledge, the effect of OT administration to both patients and therapists on the
therapeutic process was never tested. Several studies have examined the influence of
different types of substances on caretakers. For example, Modafinil administration was found
to improved cognitive performance of emergency physicians following overnight shifts. Another
study tested the influence of melatonin administration to emergency physicians working
nightshifts and found a modest improvement in their day sleep and night alertness. Substance
administration to caregivers is therefore possible, and could, in some cases, provide further
knowledge about the caregiving dynamics. Since we know the therapist's characteristics effect
the therapeutic alliance and that OT is associated with the therapeutic alliance,
patient-therapist bond, and therapy outcome, we are led to ask if OT administration to
patients and therapists could allow for a deeper understanding of OT's effects on the
therapeutic process.
Another variable found to be associated with the therapeutic process is Physiological
Synchronization. Physiological Synchronization (PS) is a primarily interpersonal phenomenon
which includes coordination of physiological signals between two or more interacting
individuals. In other words, PS involves two individuals or more who mutually impact one
another to the point of synchronizing, without necessary physical or visual contact. It has
been suggested that PS originates during intra-uterine life between mother and fetus and to
maintain through the entire human lifespan. Despite the rising number of studies examining
PS, its physiological and psychological mechanisms are yet to be fully understood. Recently,
Feldman (2020) has offered a model linking synchronized behavior, affiliative processes, and
OT, arguing that these three components function in the service of a superordinate meaning
system responsible for Human Resilience. However, to the best of our knowledge, the
hypothesis of OT as the mediating neuro-hormone of PS is yet to be tested.
Based on literature indicating associations between OT and PS, and associations each of them
has with the therapeutic process and its facilitators, in this study we wish to examine the
influence of OT on PS through intranasal OT administration to patients alone and to patients
and therapists together.
Research Hypotheses
1. Patients receiving OT will demonstrate higher levels of PS during the measured session
compared to patients receiving placebo.
2. Patients receiving OT will report higher levels of perceived therapist empathy as
compared to patients receiving placebo.
3. These associations will be stronger when both patient and therapist receive OT in
comparison to patient alone.
4. Changed in PS and empathy will be associated with OT even after controlling for patient
rated alliance and session impact.
5. These findings will sustain after controlling for severity of symptoms and attachment
patterns.
Importance of the study The uniqueness of the proposed study is rooted in the view of the
psychotherapy dyad as undetached, by focusing on the dyad and not on the patient alone.
Focusing on patient-therapist synchronization lies on the understanding of the
patient-therapist bond as co-dependent and co-affected. Such research could increase our
understanding of PS between patient and therapist and its meaning in psychotherapy research
and practice. Furthermore, the implications of such study could facilitate the understanding
of the mechanisms of change in psychotherapy in a way that could be manipulated in the
future.
Method Participants Sixty patients and their therapists will be recruited for the pilot
study. Patients will be recruited from the inpatient adult psychiatric wards at Shalvata
Mental Health Center. Inclusion criteria is: (a) age above 18. (b) any type of psychiatric
illness. (c) hospitalization in one of the inpatients wards. Patients will be excluded from
the research if they (a) are going through a severe psychotic episode, or (b) if pregnant
according to self-report. Therapists in this study will be comprised of psychologists,
psychiatrists, and social workers, in different stages of seniority and training. Therapists
will be excluded from the study if pregnant according to self-report.
Instruments Attachment and outcome measurements are assessed for statistical control, and the
therapeutic process measurements - therapeutic alliance, perceived empathy and session impact
- are the dependent variables.
The Hopkins Symptom Checklist. A self-report questionnaire measuring symptoms of depression
and anxiety. The HSCL-11 is a brief version of the SCL-90-R and it includes 11 items
assessing symptomatic distress. The HSCL-11 is highly correlated with the Global Severity
Index (r = .91) and has high internal consistency. The measure will be utilized at baseline
to assess baseline levels of distress.
The Experience in Close Relationship Scale (ECR). A self-report questionnaire evaluating
anxious and avoidant attachment in adults. It consists of 36 items divided to two dimensions:
18 items reflecting anxious attachment, while the other 18 items reflecting avoidant
attachment. Participants indicate the extent to which they agree/disagree with each item in
terms their general experience of close relationships on a 7-point scale ranging from not at
all (1) to very much (7). Reliability and validity of the ECR have been repeatedly
demonstrated. The measure will be utilized at baseline to assess attachment patterns.
The Working Alliance Inventory - Short Revised (WAI - SR). A self-report questionnaire that
aims to evaluate patient-therapist working alliance through three aspects: agreement on
therapy goals, agreement on therapeutic tasks and patient-therapist positive emotional bond.
The WAI-SR is a brief version of the original 36-item WAI, and an extended version of the
6-item Working Alliance Inventory (WAI-6). The WAI-SR consists of 12 items rated on a 6-point
scale ranging from not at all (1) to very much (6). The questionnaire has two versions: one
assessing the alliance from the patient's point of view and the other assessing it from the
therapist's point of view. This measurement was translated to hebrew and has demonstrated
excellent reliability, convergent validity, and predictive validity.
The Barrett-Lennard Relationship Inventory - Empathy Scale (BLRI). A self-report
questionnaire that relies on Rogers' (1957) four essential components for the achievement of
positive therapeutic change: empathic understanding, level of regard, unconditionality of
regard and congruence. Together, these components form four sub-scales, each consists of 16
items, 64 items in total. For the porpuses of the current study, the empathy sub-scale will
be utilized. The sub-scale consists of 16 items and is rated in a 6-point scale. The
questionnaire has two versions: one measuring the perceived empathy of others towards me,
which will be filled by the patient, and another measuring "my perceived empathy for others",
which will be filled by the therapist. The measure was found highly reliable, with internal
consistency of 0.91 for the entire questionnaire, and 0.83 for the empathy sub-scale.
Session Evaluation Questionnaire (SEQ). A self-report questionnaire assessing the effects of
a psychotherapy session through different aspects of the patient's views and feelings
regarding the session. It consists of a 7-point scale of 20 bipolar adjectives (for example -
1-"sad" ranging to 7-"happy"). The adjectives refer to two dimensions: session (for example -
"the current session was…") and post-session (for example - "now I'm feeling…"). The SEQ is
divided to four sub-scales of session and post-session: depth, flow, awareness and
positivity. The depth sub-scale measures perceived efficacy and value of the session; the
flow sub-scale measures perception of comfortability, calmness and peacefulness of the
session; the awareness sub-scale measures the extent of energetic feeling post-session; the
positiveness sub-scale measures the extent of positive feeling post-session. The SEQ
demonstrated high internal consistency (α = .90) alongside high validity.
Side-effects questionnaire. A self-report scale aimed to assess potential side effects of
IN-OT based on reports from past studies. It consists of 18 usual and unusual possible
treatment side-effects. The questionnaire was constructed in order to provide indications of
side-effects which might warrant additional safety considerations.
Electrodermal Activity (EDA). PS will be measured by the recordings of the electrodermal
activity (EDA) signals using a galvanic skin response (GSR) device. The GSR device requires
the attachment of two wireless electrodes to the subject's fingers. EDA was chosen due to
recent developed analytic approaches for computing and interpretating PS processes based on
EDA data. The AMIco algorithm identifies the picks and valleys in the EDA curves of the
patient and therapist and tests their compatibility. The algorithm maximizes the probability
of EDA correlation identification.
Oxytocin Administration. Intra-nasal OT (IN-OT) will be performed using a spray containing
24IU (12IU administered to each nostril), sorbitol, benzyl, alcohol glycerol, distilled
water. Control group (PLC) will be administered using the same spray, containing the same
components but the OT. Dosage and administration method was determined by standard OT studies
guidelines. The two substances will be prepared immediately after randomization by an
external trained nurse who has no relations to the study. The nursing staff will administer
the substance after proper training by the chief hospital pharmacist and principal
investigator.
Procedure Sixty patients meeting inclusion criteria and their therapists will be recruited
for the pilot study. Dyads will be randomized and double-blindly allocated to receive
intra-nasal oxytocin or placebo. Dyads will be followed for two consecutive sessions,
approximately at their fourth and fifth sessions. After signing informed consent forms,
patients and therapists will complete therapeutic process measurements, and patients will be
assessed for the severity of their symptoms and attachment patterns. Prior to the first
session, patients will be administrated with either IN-OT or PLC and will wait for 30 minutes
before the beginning of the session. Skin conductance synchrony will be measured during the
session. At the end of the session, therapeutic process measurements will be assessed in both
patients and therapists, and patients will complete a side-effect questionnaire. Prior to the
second session, both patients and therapists will receive either IN-OT or PLC (each dyad will
receive the same substance) and will wait for 30 minutes before the beginning of the session.
Skin conductance synchrony will then be measured during the session. At the end of the
session, therapeutic process measurements will be assessed in both patients and therapists
alongside with a side-effect questionnaire.
Patient safety and study ethics Studies have shown that OT administration has very low
potential side-effects. 5-6% of the subjects reported an increase in calmness and euphoria
sensations, lightheadedness and a headache, while 3% of the subjects reported stimulated
nostrils resulting from the spray administration and dry mouth. Importantly, previous studies
gave evidence that OT does not harm the effectiveness of standard antidepressant medication.
To ensure optimal safety, the side effects profile will be evaluated throughout the
intervention period by the treating psychiatrist, and participation will be ceased if needed.
Ethically, participants will be well informed of the possibility to drop out from the study
at any time. Additionally, patients will be informed that dropping out will not affect the
treatment they are receiving, and that the information gathered from them will not be
accessible to their therapists.
Statistical Strategy To provide initial assessment of IN-OT's effectivity compared to PLC, we
will perform a comparison between the clinical courses of each dyad, using Jacobson and Truax
(1991) approach for Reliable Clinical Change (index). Cohen's d will be used for effects
sizes. Differences in effectivity will be demonstrated in Cramer's V, as indicators for
effects sizes. Physiological Synchronization will be assessed using Truth and Bias models.
All statistical analysis will be performed using SPSS software and R software.
