Evaluation of a group compassion-based program for perceived social isolation and depression in family caregivers of patients with multiple sclerosis: study protocol for an open-label randomized controlled trial

Abstract

Background

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system that causes neurologic disabilities. People with MS may need continuous care from a family caregiver. Caring is associated with physical and mental challenges, including mental health problems such as social isolation and depression. The health of patients is influenced by their caregivers’ health status. Therefore, this is a serious challenge faced by nurses in family-centered nursing care. Effective interventions, such as compassion-focused therapy (CFT), are needed to help caregivers continue caregiving and retain their health. The current study aims to evaluate the effects of a group CFT-based program on perceived social isolation and depression among family caregivers of people with MS.

Methods

The current study will employ a two-arm, parallel-group randomized controlled trial design. Sixty family caregivers will be recruited via convenience sampling and then allocated into two equal groups. The participants in the intervention group will enroll in six weekly sessions of CFT-based psychoeducation, whereas the participants in the control group will receive no intervention. Data will be collected via a form for demographic information, the UCLA LS3, and the BDI-II at baseline, after intervention, and 2 months after the end of the program. Statistical analysis will be carried out using descriptive statistics, independent t-test, repeated measures ANOVA, and ANCOVA.

Discussion

Previous studies have shown CFT effectiveness in several issues experienced by family caregivers, but its impact on social isolation and depression in family caregivers of people with MS is unknown. This study is the first to evaluate the effectiveness of CFT on social isolation and depression in family caregivers of people with MS, expanding our knowledge about CFT and caregiving challenges.

Trial registration

Iranian Registry of Clinical Trials IRCT20230823059233N (https://irct.behdasht.gov.ir/trial/73412). Registered on 1 November 2021. Protocol version: Current protocol: Version 1 (28 October 2024).

Supplementary Information

The online version contains supplementary material available at 10.1186/s13063-026-09547-0.

Background

Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease of the central nervous system [1]. With a predominantly young onset, MS is a leading cause of neurological disabilities in younger adults [2]. Currently, approximately 2.8 million people are diagnosed with MS. Approximately 75,000 people with MS live in Iran, mostly women, with an average age of 32 years at the time of onset [3]. Although the exact underlying cause of the disease is unknown, a variety of factors, including genetic elements and environmental exposures, such as infections and smoking, are known to be involved in MS pathogenesis [4]. Given the disabling nature of the disease, people with MS require continuous care and support [5].

Caring may be delivered by various providers, from in-home caregiving companies to the relatives of people in need. Informal caregivers, or more commonly known as family caregivers, refer to family members who are well aware of and respond to the patient’s needs and do not expect payments in return [6]. The care of patients at home alongside other family members as much as possible is an important global policy [7]. Family caregivers usually experience different challenges depending on their age and relations to the patients [8]. Given the burden of caregiving, family caregivers may experience mental and physical health problems, resulting in heavy physical, mental, social, and economic challenges for family members [9].

Studies have shown that MS patients, because of misconceptions about the disease, fear of being pitied, visible disabilities caused by the disease, stigmatization, and economic problems, avoid social interactions, which in turn causes their caregivers to be socially isolated [10, 11]. Another study indicated that cognitive impairments of MS patients, such as memory problems, may interrupt their social interactions and render them and their spouses socially disconnected [12]. A study conducted in Iran revealed that one of the main problems experienced by MS patients is social isolation, which is influenced by numerous factors, one of which is potentially the Islamic teachings of family commitment in Iran [10].

Social isolation and loneliness have been linked to serious health outcomes, even increasing the risk for mortality [13, 14]. Not only both social isolation and loneliness are associated with all-cause mortality [15], The American Heart Association suggests that social isolation is associated with a greater risk of cardiovascular diseases. It also affects mental health, with depression and anxiety being among the most prevalent outcomes [16, 17].

Depression is a mood disorder characterized by feelings of sadness, guilt, loss of pleasure, objective signs of irritability, decreased levels of energy, and eating or sleeping disorders for more than 2 weeks [18, 19]. While decreased or loss of social interactions is linked to depression, evidence suggests that depression may also result in social isolation, which is expected as the depressive symptoms can affect beginning, maintaining, and terminating social connections [20]. Studies indicate that depression is a common issue experienced by caregivers of people with MS [8]. This is highly important because depression increases caregiving strain and fatigue, and therefore significantly impacts the quality of life as well as the mental and physical health of caregivers [21].

Given the interrelation of social isolation and depression, and their impact on caregivers’ health, effective interventions are required to optimize the caregiving process. A large body of suggested interventions exists [22, 23]. Compassion-focused therapy (CFT) is a promising psychotherapy for psychological conditions [24].

Although not universally agreed upon, compassion is usually defined as “sensitivity to suffering in self and others with a commitment to try to alleviate and prevent it.” [25, 26]. This concept was originally emphasized in the Buddhist tradition, which considers it a way to achieve happiness and enlightenment, leading the “compassionate” person to positive changes [27]. Compassion is actually an adaptive capacity that has helped humans regulate negative emotions to survive during their evolution [28]. Studies suggest that compassion can be taught, reinforced, and trained via education [26, 29, 30]. The teachability of compassion, along with the insufficiency of cognitive behavioral therapy (CBT) to improve negative emotions, such as self-criticism, in clinical cases was the basis and origin of CFT [31]. Compassion, although teachable, originates from the neurophysiology of the human brain; receiving kindness and compassion in early childhood enhances neural connections associated with compassionate behavior later in life [13].

CFT does so by helping the client understand that the mind is not a total product of what they have chosen or done in their lives [32]. It strengthens the ability of the client to acknowledge and confront the feelings and thoughts, and not to avoid them [33]. In other words, the purpose of CFT is not to disregard suffering, but to deal with it [34]. In fact, CFT holds that pain and suffering are inseparable parts of human life [35].

The undesirable outcomes of social isolation and depression for family caregivers raise concerns for family-centered care. The current literature considers supporting families and caregivers of patients with MS as one of the key roles of clinical nurses. Therefore, nurses are required to learn and employ a variety of skills to support and enable families and caregivers of people with MS [36, 37]. CFT may be an effective nursing intervention to improve caregivers’ and eventually patients’ conditions.

Given the success of CFT in improving a wide range of psychological issues, including depression, and the importance of mental health in family caregivers on their care quality, the current study examines whether CFT can be employed as a psychoeducational nursing intervention to improve the perceived social isolation and depression of family caregivers of people with MS compared with a control group of the same caregivers that receives no intervention.

Methods

Objectives

The current study aims to evaluate the effectiveness of a group compassion-based program on the perceived social isolation and depression of family caregivers of people with MS. We hypothesize that CFT will significantly improve both outcomes in caregivers in the intervention group compared with participants in the control group. We also hypothesize that the improvement will last at least 2 months after the intervention.

Study design

This study is an open-label two-arm parallel-group randomized controlled trial with an intervention group in which participants receive a group compassion-based psychoeducational program and a control group with no intervention. Using a superiority framework, it is hypothesized that the intervention will yield superior outcomes compared to the control group. The allocation of participants will be randomized at a 1:1 ratio. We used the SPIRIT checklist when writing our protocol (Fig. 1; Additional file 1) [38].

Fig. 1.

SPIRIT guidance figure

Study settings

The participant will be recruited from Al-Zahra and Kashani hospitals, two centers with specialized MS clinics in Isfahan, Iran. The CFT-based program for the intervention group is planned to be delivered in the classrooms of Kashani hospitals, two centers with specialized MS clinics in Isfahan, Iran. Both hospitals are referral centers affiliated with Isfahan University of Medical Sciences. People with MS are referred to these centers for treatment follow-up, periodic appointments, and, in some cases, drug administration.

Participants and sampling

Family caregivers of people with MS referred to the selected hospitals will be recruited via convenience sampling. The required sample size was calculated on the basis of standard deviations of depression scores in a previous similar study [39]. With S₁ and S₂ being the standard deviations of the depression scores in the intervention and control groups, given that the minimum reduction in the mean depression score was 8 units, a 95% confidence interval and 90% power, 25 participants are required for each arm of the study. Considering 20% attrition, a total of thirty family caregivers who meet the eligibility criteria will be recruited for each arm.

$$N=\frac{(Z_{1-\frac{\alpha }{2}}+{Z_{1-\beta })}^2(S_1^2+S_2^2)}{{({\mu }_1-{\mu }_2)}^2}$$

$$\begin{array}{c}\hfill (S_1=8.77,S_2=8.71,{\mu }_1-{\mu }_2\\ \hfill =8,Z_{\alpha /2}=1.96,Z_{1-\beta }=1.28)\end{array}$$

Recruitment and consent

VS will introduce the eligible participants to FN. Family caregivers of patients referred to the selected hospitals will be interviewed during their patients’ appointments. FN will briefly share the objectives and procedure of the study with their caregivers. If they are unwilling, the interviewed caregivers will not be included in the study. If willing, and if the interviewed caregivers meet the inclusion criteria, their contact information will be obtained for further steps. FN will take informed, written consent from participants in both groups later in an introductory session.

Eligibility criteria

The inclusion criteria for caregivers are as follows: (1) aged between 18 and 70 years, (2) a minimum level of literacy needed for reading and writing, (3) consent to participate in the study, (4) if the patient has more than one caregiver, the caregiver who spends more time with the patient, (5) having the physical ability to participate in class sessions for at least 2 h, (6) having the mental capacity to participate in the educational program without a self-reported learning or memory disorder, (7) having no history of depression or any other disease affecting social interactions, and (8) being the caregiver of only one patient. Unwillingness to continue to participate, absence in class sessions for more than two sessions, and diagnosis of depression or any other disease affecting social interactions during the study will result in exclusion from the study. Excluded participants will be allowed to attend the class session despite their exclusion from the analysis. Although participants were not discouraged from participating in other psychological or psychiatric interventions in other clinical trials, their participation would result in their exclusion from the study. However, the usual care provided by the selected centers was permitted.

Although family caregivers are the actual participants in this study, we also considered eligibility criteria for patients, as the situation of patients directly affects the caregiving process and outcomes. Patients are people diagnosed with MS according to the McDonald criteria [5] by a licensed neurologist. We will include family caregivers of patients with an expanded disability status scale (EDSS) score ranging from 2 to 9.5, no history of other chronic diseases, and who have been diagnosed with MS for at least 6 months. Caregivers of patients who expire or are admitted to a hospital due to a relapse during the study will be excluded.

Outcomes and materials

Perceived social isolation and depression are the primary outcomes of this study. The primary outcomes will be measured at baseline (i.e., before intervention, T₀), immediately after intervention (i.e., after the last session of intervention, T₁), and 2 months after the intervention (i.e., the follow-up, T₂). All measurements of primary outcomes will be reported as the mean score and standard deviation. We also obtained the demographic information of the caregivers, including their age, sex, marital status, relationship with the patient, education, and employment status, and disease information of their patient, including disease duration, disease pattern, and EDSS score. These data are the background variables of the study.

Instruments and data collection

The background data, including demographic information of the caregivers and disease information of the patients, will be collected at baseline via a form developed by the researchers. The EDSS score of patients may need a physical examination as it is sometimes not recorded in patients’ files. Perceived social isolation and depressive symptoms, which are the primary outcomes of the study, will be measured at T₀, T₁, and T₂. Each primary variable will be analyzed independently.

Perceived social isolation will be measured by Russell’s UCLA Loneliness Scale Version 3 (UCLA LS3). This questionnaire was originally developed in 1978 and was later revised by Russell in 1996 because the scale was criticized for the negative phrasing of all items, as it could create bias for respondents. UCLA LS3 consists of twenty items; eleven items are negatively phrased (i.e., implies feeling excluded), and the rest are positively phrased. The Likert score of negatively phrased items ranges from 1 (“Never”) to 4 (“Always”). The positively phrased items are scored oppositely. A higher score indicates greater perceived isolation. UCLA LS3 has shown good psychometric performance in the original study [40]. The Persian translation of the UCLA LS3 has been validated via factor analysis and shown to be reliable, with a Cronbach’s alpha of 0.91 [41].

The Beck Depression Inventory (BDI-II) will be used to measure depression. Originally developed in 1961 and later revised in 1996, this 21-item scale is a widely used instrument to quantify depression, including depressive mood and symptoms. Each item of the BDI-II is scored from 0 to 3, for a total score between 0 and 63. A higher score implies more severe depression [42]. The validity and reliability of the BDI-II were evaluated and confirmed by Beck et al. [43]. The construct validity of the Persian translation of the BDI-II is confirmed by convergent validity and factor analysis. It has also been shown to be internally consistent, with a Cronbach’s alpha of 0.91 [44].

Data will be collected before and after the intervention and a 2-month follow-up. The UCLA LS3 and BDI-II questionnaires will be printed and delivered to all participants. To collect data at baseline (T₀), all participants will be invited to a session held at Kashani Hospital. After receiving a detailed explanation of the study procedure and providing informed consent, the participants will complete the printed questionnaires as well as the forms of demographic information and disease information. At the end of the last session of the program (T₁), the UCLA LS3 and BDI-II questionnaires will again be delivered to the participants. At the follow-up (T₂), the questionnaires will be delivered to the participants one last time. The timing and instruments of data collection are the same for all participants, regardless of their assignment to the intervention or the control group. Data monitoring in all phases will be performed by FN.

Study procedure

After recruitment reaches the calculated sample size, a number between 1 and 60 will be sequentially assigned to each participant. All numbers will be subsequently entered into the random allocating tool of the GraphPad website (available at www.graphpad.com). The random allocator will assign the numbers into two separate groups. One group will be randomly considered the intervention group, and the other group will be considered the control group (Fig. 2). The entire allocation process, including the generation of the allocation sequence and participant assignment, will be implemented by FN.

Fig. 2.

Flow diagram showing the study procedure

All participants will be invited to an in-person, introductory session held at the Kashani Hospital classroom via the contact information previously obtained during recruitment. The objectives, procedure, date, and time of the following sessions will be shared and discussed in this session in full detail. Informed, written consent will be obtained from all participants by FN. Furthermore, baseline data will be collected (T₀). At the end of this session, participants in the control group will be discharged and asked to wait until the end of the intervention. The participants in the intervention group will be divided into three equal subgroups of ten participants. Caregivers in each subgroup will participate in six weekly 120-min sessions held in the classrooms of the selected centers. FN will be responsible for psychoeducation. FN has been trained and certified to devise a CFT-based psychoeducational program. SB, who has contributed to similar studies exploring compassionate nursing care [45], will be the supervisor and advisor of the intervention.

After the sixth and final session of the program (T₁), social isolation and depression will be measured in all participants via the UCLA LS3 and BDI-II. Two months after the final session (T₂), as a follow-up to determine the long-term effectiveness of the program, participants in both groups will be asked to fill out the questionnaires for the third time. During the follow-up period, no intervention will be delivered to either group. The collected data will be entered into IBM SPSS Statistics version 24 for data analysis.

At the end of the study, if the intervention proves to be effective, recorded materials of all sessions will be shared with the participants in the control group.

Intervention

The intervention consists of six weekly 120-min sessions, each of which will be delivered in classrooms of the Kashani Hospital. We chose this timing frame because the strongest effects in previous interventions have been associated with programs with durations over 12 h [46]. The program is a psychoeducational CFT intervention developed primarily based on Gilbert’s protocol [27] (Table 1). We incorporated homework-based skill-building into the CFT program outlined by Gilbert, with elements of Neff’s account of self-compassion, to ensure the comprehensiveness of our program. The entire content is delivered via face-to-face education, a PowerPoint presentation, pamphlets, and group discussion. Each session consists of a brief review of the previous session and a 10-min break. Furthermore, homework, which is a practice that needs to be trained at home, will be given to participants at the end of each session. The researcher will be available via phone call for participants between the sessions for any questions or issues they may experience. Each participant will be asked to verbally report his experience with the homework in the next session.

Table 1.

The subject and content of each session of the CFT-based psychoeducational program in this study

Session	Content	Homework
0	A detailed introduction to the study procedure, taking informed consent, and baseline assessment	No homework
1	Preliminary communication, a review of the following sessions, introduction to “compassion,” its general principles and basic concepts	Writing a compassionate letter
2	Mindfulness basics, soothing breathing, and body scanning	Mindfulness practice
3	Characteristics of a compassionate person	Introspection to search for characteristics of a compassionate person, and rating them
4	“Compassionate skills” and how to cultivate these skills	Skill-building exercises
5	Readiness and acceptance of future events	Self-teaching practice
6	A review of previous session; how to write down a compassionate letter	Writing a compassionate letter, and comparing it to the one written after session 1

To encourage participants to enroll in class sessions, every session will include an evening meal. The sessions will be free of charge. The participants will be free to contact FN at any time. They are allowed to ask their questions, report on their homework, or any other problems they may face during the study.

The content of each session is presented in detail in Additional file 2.

Data analysis

Descriptive statistics, including means and standard deviations for quantitative data, and frequencies and percentages for qualitative data, will be used to describe demographic and disease-related variables. The normality of the data will be tested via the Shapiro-Will test. Within-group analyses and between-group comparisons will be implemented independently for each outcome variable. Independent t-test will be used to determine the significance of the difference in outcome scores between the intervention and control groups at T₀, T₁, and T₂. Repeated measures ANOVA will reveal if there are any significant changes in the mean scores of each group from T₀ to T₂. ANCOVA will be employed to control for baseline scores and adjust for mean scores between groups. All tests will be two-tailed, and a p value of < 0.05 will be considered statistically significant. IBM SPSS Statistics version 24 will be used for data entry and all analyses. FN will enter the gathered data into the spreadsheet of SPSS for data analysis based on the numbers assigned to participants in recruitment.

The data analysis will be per protocol, excluding the missing data related to any study participant from the final analysis at each time-point. Therefore, participants failed to participate in post-test measures or lost to follow-up will be excluded from data analysis. However, the background data will be presented for all participants allocated to each group regardless of their participation.

Discussion

The main question of the current study is whether CFT, as a group psychoeducational program outlined above, is effective in improving social isolation and depression among family caregivers of people with MS. Only one similar study was found to evaluate the effects of CFT in caregivers of patients with MS. A study conducted in Tehran, Iran, showed that a CFT program consisting of eight 1-h sessions significantly increased resilience and quality of life in caregivers of people with MS [47]. To our knowledge, this study would be the first evaluation of the effects of CFT on social isolation and depression in family caregivers of people with MS.

Loneliness has also been subject to CFT-based intervention [48, 49]. Although effective, to our knowledge, no study has evaluated the effectiveness of CFT on loneliness among caregivers. Given the close link between feelings of loneliness and perceived social isolation, we hypothesize that the intervention in the current study will effectively reduce perceived social isolation in caregivers of people with MS.

Psychoeducational group interventions are beneficial in many aspects. They are usually inexpensive, cost-effective, and easy for institutions to conduct. Skill-building, which is a component of these interventions, including the program in the current study, helps clinical populations learn the skills necessary for coping, decreasing the need for referrals to psychologists and psychiatrists. These interventions have been proven to be effective in facilitating social interaction and creating peer groups [50].

However, some limitations will remain in this study. We will use a convenience sampling method, by which participants are referred by a single neurologist who participates in the study. This would limit the generalizability of the results. Furthermore, because of the nature of the intervention, we were unable to blind the participants to the study. Despite these limitations, the researchers in the current study are committed to collecting data rigorously and conducting the study as described in this paper to ensure the precision and reliability of the results.

We believe that the results of the current study may add to the literature as it will be the first study to demonstrate the effectiveness of CFT in caregivers of people with MS, with perceived social isolation and depression as primary outcomes. Caregivers of people with MS have rarely been the target of CFT interventions in the current literature, and the current study will expand our knowledge of both CFT effectiveness and factors affecting caregiving in MS. If effective, compassion-based interventions may be justified for incorporation into comprehensive family-centered care.

Trial status

The trial is registered on 1 November 2021 in the IRCT (IRCT20230823059233N). The current paper is the first protocol version of the trial to be published. Recruitment is planned to start on 1 December 2024.

Abbreviations

BDI-II

Beck Depression Inventory Version 2

CBT

Cognitive behavioral therapy

CFT

Compassion-focused therapy

EDSS

Expanded Disability Status Scale

IRCT

Iranian Registry of Clinical Trials

MS

Multiple sclerosis

UCLA LS3

UCLA Loneliness Scale Version 3

Authors’ contributions

The researchers involved in this study meet authorship eligibility criteria, as their involvement will be substantial in the study implementation. Fatemeh Nabi (FN) conceived the study. She will be responsible for data collection, analysis, recording meeting reports, assessing the participants, and providing written informed consent. She also wrote drafts of the manuscript. Hojatollah Yousefi (HY) initiated the study design and development of the protocol. Sima Babaee (SB) was involved in the intervention design. She will also supervise the sessions. HY and SB supervised the writing of the manuscript. Vahid Shaygannejad (VS) will refer family caregivers to FN, who will assess them for eligibility. HY will be responsible for all aspects of the Research Ethics Committee of Isfahan University of Medical Sciences and will report the updates to the Iranian Registry of Clinical Trials. All authors contributed to the refinement of the study protocol and approved the final manuscript.

Funding

The trial will be funded by the Vice Chancellery for Research and Technology of Isfahan University of Medical Sciences (Address: No. 81746-73461, Hezar Jerib Street, Isfahan, Iran; E-mail: research@mui.ac.ir; Tel: +98-31-36687898). Although the Research Ethics Committees of Isfahan University of Medical Sciences will provide financial support and supervise the intervention, the researchers will conduct the study independently of the funder. The funding body will not be involved in data collection and analysis.

Data availability

The results will be subsequently published after analysis, and the data will be available upon reasonable request.

Declarations

Ethics approval and consent to participate

The Research Ethics Committees of Nursing, Rehabilitation, and Management Schools of Isfahan University of Medical Sciences approved this study (IR.MUI.NUREMA.REC.1402.128). The study procedure has been designed and will be implemented in accordance with the ethical standards of Isfahan University of Medical Sciences. Written, informed consent to enroll in the study will be obtained from all participants by FN (Additional file 3). The trial is registered in the Iranian Registry of Clinical Trials (IRCT20230823059233N). Any changes to the materials and methods will be reported in the IRCT registration update.

The Research Ethics Committees of Nursing, Rehabilitation, and Management Schools of Isfahan University of Medical Sciences will inspect the implementation of the trial independent from both investigators and the funding body. The frequency and procedures for auditing trial conduct will be determined by the Research Ethics Committees.

Consent for publication

Not applicable.

Competing interests

The authors of this study declare that they have no conflicts of interest.