An interventional study of Caregiver training and administration of SAFE scale and Standard clinical care in Caregiver Anxiety, Acquired Brain Injury and Caregiver Satisfaction and Connectedness to Clinic, sponsored by Fondazione Don Carlo Gnocchi ETS. Recruiting at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-03.
Sponsored by Fondazione Don Carlo Gnocchi ETS · Not applicable, Interventional, and Supportive care
Patients with severe acquired brain injury (sABI) and disorders of consciousness (DoC) require intensive interdisciplinary rehabilitation involving healthcare professionals, patients, and family caregivers. Caregivers play a key role in supporting patients and ensuring continuity of care, yet they frequently experience high levels of psychological distress, anxiety, depression, caregiver burden, and reduced quality of life. Previous studies have highlighted the need for clearer communication and greater caregiver involvement throughout the rehabilitation process.
The Social and Family Evaluation (SAFE) scale was developed to actively involve caregivers in monitoring patients with DoC. Derived from the Coma Recovery Scale-Revised (CRS-R), SAFE is a simplified, caregiver-friendly observational tool that enables family members to report clinically relevant behaviors observed during daily interactions. Preliminary validation demonstrated excellent psychometric properties, including high internal consistency, excellent test-retest reliability, and good criterion validity compared with the CRS-R. However, its effectiveness has not yet been investigated in the subacute rehabilitation setting.
The primary aim of this study is to evaluate whether the use of the SAFE scale improves caregivers' illness perceptions. Secondary objectives are to assess its impact on caregiver satisfaction with rehabilitation, decisional conflict, anxiety, depression, prolonged grief, and caregiver burden.
This is a non-profit, prospective, multicenter, single-blind randomized controlled trial involving 68 caregiver-patient dyads recruited from three intensive neurorehabilitation units of the Don Carlo Gnocchi Foundation in Florence, Milan, and Sant'Angelo dei Lombardi (Italy). Adult caregivers of patients with DoC admitted within three months after brain injury will be randomly assigned (1:1) to either the SAFE intervention group or a standard-care control group. Randomization will be stratified according to caregiver relationship (parent vs. non-parent) and patient diagnosis (vegetative state/unresponsive wakefulness syndrome vs. other DoC).
At baseline (T0), caregivers will complete the Brief Illness Perception Questionnaire (BIPQ), Family Strain Questionnaire (FSQ), Prolonged Grief Disorder-12 (PG-12), Beck Depression Inventory-II (BDI-II), and State-Trait Anxiety Inventory (STAI-Y). Patients will be assessed using the Coma Recovery Scale-Revised (CRS-R) and the Level of Cognitive Functioning (LCF).
Caregivers allocated to the SAFE group will receive standardized training on the SAFE scale and complete it at 2 weeks (T1) and 6 weeks (T2), together with repeated BIPQ assessments. Control participants will receive routine clinical care and complete the BIPQ only. Both groups will receive the same psychoeducational booklet as standard care.
At the final follow-up (T3, 10 weeks after enrollment), caregivers will repeat all baseline assessments and additionally complete the Family Satisfaction in Intensive Care Unit (FS-ICU) and the Decisional Conflict Scale (DCS). Patients will undergo repeat CRS-R and LCF assessments together with the Glasgow Outcome Scale-Extended (GOSE).
The primary endpoint is the BIPQ Illness Coherence score at T2. The primary analysis will use ANCOVA adjusted for baseline values. Based on preliminary data, 68 caregivers will be enrolled to detect a clinically meaningful difference between groups while accounting for an expected 20% dropout rate. A blinded sample-size re-estimation will be performed after recruitment of the first 30 participants.
Secondary analyses will evaluate the effects of the SAFE intervention on caregiver burden, prolonged grief, anxiety, depression, family satisfaction, and decisional conflict using adjusted statistical models.
The study is considered low risk, as all procedures are consistent with routine clinical practice. If effective, the SAFE scale may enhance caregiver understanding of the patient's condition, improve communication with the rehabilitation team, promote shared decision-making, reduce psychological distress, and support a more family-centered approach to neurorehabilitation.
The diagnosis and monitoring of disorders of consciousness rely primarily on standardized behavioral assessment performed by trained clinicians. Although the Coma Recovery Scale-Revised (CRS-R) represents the current clinical reference standard, patient responsiveness may fluctuate considerably throughout the day, and clinically meaningful behaviors may occur outside scheduled assessments. Family caregivers, who spend prolonged periods with patients across different contexts, are uniquely positioned to observe subtle behavioral changes that might otherwise remain undocumented.
The Social and Family Evaluation (SAFE) scale was specifically developed to facilitate the structured collection of these caregiver observations using terminology and response options accessible to non-healthcare professionals. Rather than replacing clinician-administered assessments, SAFE is intended to complement routine neurological evaluation by promoting systematic communication between caregivers and the multidisciplinary rehabilitation team. Integrating caregiver observations into the rehabilitation pathway may improve the continuity of behavioral monitoring while fostering a shared understanding of the patient's clinical condition.
In addition to its potential diagnostic value, the structured use of SAFE may represent a communication intervention. By providing caregivers with a common framework for interpreting patient behaviors, the scale may facilitate discussions with healthcare professionals, improve understanding of the diagnostic process, and encourage more active participation in rehabilitation. These mechanisms are expected to influence caregivers' illness perceptions, reduce uncertainty surrounding the patient's condition, and strengthen therapeutic alliance with the rehabilitation team.
This study will also provide evidence regarding the feasibility of implementing SAFE within intensive neurorehabilitation units during the subacute phase following severe acquired brain injury. The findings will contribute to understanding whether a standardized caregiver-reported assessment can be integrated into routine clinical practice while supporting family-centered care and enhancing communication between families and healthcare professionals.
2,127 studies on the registry are indexed under Brain Injuries; 386 are open to participants now.
This study's planned enrollment of 68 is above the median of 48 across 1,343 interventional studies indexed under Brain Injuries.
Browse Brain Injuries studies →Fondazione Don Carlo Gnocchi ETS is the lead sponsor of 42 studies on the registry; 26 are open to participants now.
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Caregiver Inclusion Criteria:
Caregiver Exclusion Criteria:
Patient Inclusion Criteria:
Patient Exclusion Criteria:
None.
Participants allocated to the SAFE group will undergo an individual training session with the healthcare professionals involved in the study. During this session, the SAFE scale and its administration procedures will be explained in detail. According to the procedures established for the SAFE scale, caregivers will complete the scale after a 2-week observation period of the patient's behaviours (T1). The SAFE scale will then be completed again by the caregiver 4 weeks after the first administration (corresponding to 6 weeks after the initial training session performed at baseline, T2). Caregivers will be asked to complete also the following questionnaire: Brief Illness Perception Questionnaire (BIPQ; Broadbent et al., 2006)
Behavioral: Caregiver training and administration of SAFE scale
Participants allocated to the NO-SAFE group will receive the standard clinical care provided by the rehabilitation unit. They will receive the Fondazione Don Gnocchi educational booklet "Il paziente con GCA: guida per le famiglie" as the minimum psychoeducational intervention. Two weeks after enrolment and delivery of the educational booklet, caregivers will be asked to complete the following questionnaire: Brief Illness Perception Questionnaire (BIPQ; Broadbent et al., 2006).
Other: Standard clinical care
The intervention will consist of caregiver training and completion of the SAFE scale (Magnani et al., 2025). The SAFE is an observational tool developed to allow caregivers of patients with Disorders of Consciousness (DoC) to systematically report cognitively mediated behaviours based on daily interactions with the patient over the previous two weeks. Derived from the Coma Recovery Scale-Revised (CRS-R; Giacino et al., 2020), the SAFE includes simplified items designed for non-professional users. Preliminary results have shown good reliability, internal consistency, and correlation with the CRS-R. Following a standardized explanation provided by trained clinicians, caregivers will complete the scale by reporting behaviours observed during the previous 15 days. For each item, caregivers will answer "Yes" or "No" regarding the presence of a specific voluntary/non-reflexive behaviour associated with sensory or cognitive domains.
Also known as: scale administration
Caregivers allocated to the NO-SAFE group will receive the standard clinical care provided by the rehabilitation unit. They will receive the Fondazione Don Gnocchi educational booklet "Il paziente con GCA: guida per le famiglie" as the minimum psychoeducational intervention and will participate in routine clinical meetings with the physicians of the rehabilitation unit.
Caregivers' Perceived Understanding of Their Relative's Clinical Condition
Measure: The primary endpoint is the score on the Illness Coherence item of the Brief Illness Perception Questionnaire (BIPQ; Broadbent et al., 2006) at T2. This item assesses caregivers' perceived understanding of their relative's clinical condition in the context of Disorders of Consciousness (DoC). The item is scored on a scale from 0 to 10, with higher scores indicating greater perceived understanding of the clinical condition (better outcome).
Time frame: 6 weeks from the enrollment
Family Satisfaction with Care
Measure: Family Satisfaction in the Intensive Care Unit (FS-ICU; Heyland \& Tranmer, 2001; Italian version: Pagnamenta et al., 2016; Danielis et al., 2023). Family satisfaction with the patient's care pathway will be assessed using the Family Satisfaction in the Intensive Care Unit (FS-ICU). The overall score ranges from 0 to 100, with higher scores indicating greater satisfaction with care (better outcome).
Time frame: 10 weeks from the enrollment (T3)
Decisional Conflict
Measure: Decisional Conflict Scale (DCS; O'Connor, 1993; Chiavari et al., 2013; Esposito et al., 2020). Decisional conflict will be assessed using the Decisional Conflict Scale (DCS). The total score ranges from 0 to 100, with higher scores indicating greater decisional conflict and uncertainty (worse outcome).
Time frame: 10 weeks after enrollment (T3)
Depressive Symptoms
Measure: Beck Depression Inventory-II (BDI-II; Beck et al., 1996; Steer, 1999; Ghisi et al., 2006). Depressive symptoms will be assessed using the Beck Depression Inventory-II (BDI-II), a 21-item self-report measure. Total scores range from 0 to 63, with higher scores indicating greater severity of depressive symptoms (worse outcome).
Time frame: From baseline (T0) to 10 weeks after enrollment (T3)
State Anxiety
Measure: State-Trait Anxiety Inventory - Form Y, State Anxiety subscale (STAI-Y; Spielberger et al., 1997). State anxiety will be assessed using the State Anxiety subscale of the State-Trait Anxiety Inventory - Form Y (STAI-Y). The subscale score ranges from 20 to 80, with higher scores indicating greater state anxiety (worse outcome).
Time frame: From baseline (T0) to 10 weeks after enrollment (T3)
Trait Anxiety
Measure: State-Trait Anxiety Inventory - Form Y, Trait Anxiety subscale (STAI-Y; Spielberger et al., 1997). Trait anxiety will be assessed using the Trait Anxiety subscale of the State-Trait Anxiety Inventory - Form Y (STAI-Y). The subscale score ranges from 20 to 80, with higher scores indicating greater trait anxiety (worse outcome).
Time frame: From baseline (T0) to 10 weeks after enrollment (T3)
Prolonged Grief Symptoms
Measure: Prolonged Grief Disorder-12 (PG-12; Prigerson et al., 2009). Prolonged grief symptoms will be assessed using the Prolonged Grief Disorder-12 (PG-12). The PG-12 is a self-report measure assessing symptoms of prolonged grief. The total score ranges from 11 to 55, with higher scores indicating greater severity of prolonged grief symptoms (worse outcome).
Time frame: From baseline (T0) to 10 weeks after enrollment (T3)
Caregiver Strain
Measure: Family Strain Questionnaire (FSQ; Vidotto et al., 2009). Caregiver strain will be assessed using the Family Strain Questionnaire (FSQ). The total score ranges from 0 to 30, with higher scores indicating greater caregiver strain and psychological burden (worse outcome).
Time frame: From baseline (T0) to 10 weeks after enrollment (T3)
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