Participants
60 individuals with schizophrenia and 60 family members will be recruited and will form 60 dyads. The study protocol has been approved by the Ethical Committee (CNRIPH: 19.03.19.49332) in accordance with the Helsinki Declaration.
Written informed consent will be obtained by all participants. The study report will comply with the Consolidated Standards of Reporting Trials (CONSORT) statement and CONSORT-NPT (non-pharmacological treatments) statement.
Eligibility Criteria
Inclusion criteria for the patient group are:
1) Age between 18 and 50 years old;
2) Patient who has given written informed consent to participate in the study, as well as written consent from their guardian for patients under guardianship, and/or from the trusted person for patients hospitalized in Third Party Request Psychiatric Care, Psychiatric Care at the request of a state representative and in a care program. If the patient is under curatorship, the curator will be informed of the study;
3) Patients with a diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM 5) after evaluation by the investigating psychiatrist during the preliminary medical examination;
4) Patients who can understand, speak and read French;
5) Obligation to be a member or beneficiary of a social security scheme.
Inclusion criteria for the family member group are:
1) Be under 75 years old for the family member group;
2) Having signed an informed consent form;
3) The family carer is actively involved in the care of his or her relative with schizophrenia assessed by having at least one contact per week with the patient (Kidd et al., 2016);
4) The carer has an internet connection with a video chat application;
5) Understand, read and speak French;
6) Obligation to be a member or beneficiary of a social security scheme
Exclusion criteria for the patient group are:
1) A history of severe head injury and/or neurological pathology with cognitive impact;
2) Patient who has benefited from individual or group cognitive remediation.
Exclusion criteria for the Family caregiver group are:
1) Diagnosis of dementia;
2) A history of neurological pathology (epilepsy, multiple sclerosis, parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease).
Study Design
This study is a comparative, single blind randomized controlled, clinical trial designed to assess the efficacy of a Web-based family Cognitive Adaptation Training in individuals with schizophrenia.
Patients and family members meeting all of the inclusion criteria and none of the exclusion criteria are invited to participate in this study. After signing the consent form, they are randomized into one of the two interventions: Cognitive Adaptation Training or Psycho-education.
Patients are assessed at baseline for cognitive functioning, life skills profile, symptomatology, quality of life and medication adherence. An assessment of the living space is also carried out. This assessment allows for the identification of missing supplies for daily living tasks and living conveniences, as well as the condition of the living space including housing safety, cleanliness and maintenance.
Participants are re-assessed at 16 weeks corresponding to the end of the intervention and 6 months later (with a delay of 15 days maximum) for cognitive functioning, life skills profile, symptomatology, quality of life, assessment of the living space and medication adherence. If the intervention is delayed, this intermediate assessment is performed as soon as the intervention is completed and within 15 days of the end of the intervention.
A clinical psychologist, blind to the randomization process, performs the assessments at 16 weeks and at 6 months. Another psychologist performs the first assessments and the therapy.
Setting
Patients are recruited from Professor Capdevielle's adult psychiatric unit of the University Hospital of Montpellier, France, which includes an expert center on schizophrenia (FondationFondaMental, Pr. Capdevielle), a day hospital, and a recovery center for people suffering from schizophrenia. Recruitment also takes place within family associations. The recruitment of patients is also done among the patients followed in Pr Capdevielle's department by the different doctors and psychologists; though a referral by a psychiatrist or psychologist is not a requirement to participate. Recruitment is for outpatients only.
This study protocol has been reported in accordance with the “SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents” (Additional file 1).
Justification of the study design
This clinical trial is designed to assess the efficacy of a web-based cognitive remediation therapy including the family in patients with schizophrenia by comparing results from CIRCUS (Cognitive Remediation Program for Family Caregivers with Schizophrenia) intervention to a web-based psycho-educational program including family.
We choose a single blind study to be sure that the psychologist performing the evaluations at 16 weeks and 6 months is blinded to the randomization arm.
It is not possible for patients following Cognitive Adaptation Training to be in a blinding condition.
For the comparison group (active comparator), patients benefit from a web-based psycho-educational program that will allow us to compare two web-based interventions.
Intervention description
Parallel Assignment
Comparative, prospective, randomized, study including two groups of (patient / caregiver) dyads:
• An intervention group consisting of a dyad (patient and family carer) benefiting from the web-based CAT intervention.
• A control group consisting of a dyad (patient and caregiver) with a psycho-educational manual (control group).
Experimental Group
Cognitive Adaptation Training for Caregivers:
- 15 sessions of the CAT intervention
- 1 session per week sent by e-mail
- A 15 minute video feedback with a psychologist (different to the psychologist who performs the last assessments)
- dyad: patient and a family member
The Cognitive Adaptation Training for Caregivers has been developed by Pr. Velligan and Pr. Kidd [2]. They created a manual accessible to people without any knowledge of cognitive deficits. This manual helps families to select specific cognitive-adaptative strategies with their relative to achieve targeted goals. This method was translated in French and divided into different modules. The CAT for caregivers’ intervention is delivered according to a standardized treatment manual comprising of 14 modules addressing daily living activities over 15 sessions (Table 1). The manual includes psycho-education on common cognitive disorders in schizophrenia, setting a smart goal, and cognitive methods in different domains of daily living activities and problem solving.
One module is sent per week to the dyad (patient and family member) for reading and implementing daily. It is a collaborative discussion between the family member and the patient on how to implement these methods according to their goals. A week after receiving the manual, each dyad benefits from a 15 minute video feedback with a trained psychologist to identify the weekly goal, implement the weekly strategy and resolve any issues encountered by the dyad.
Table 1. Manual modules and therapeutic aims
Modules Content
1
|
Understanding the signs and symptoms of schizophrenia
|
2
|
Executive functioning
|
3
|
Developing a plan
|
4
|
Getting started with environmental supports
|
5
|
Basic strategies for everyday living: Overview, bathing and dressing
|
6
|
Basic strategies for everyday living: dental hygiene, applying makeup and using the toilet
|
7
|
Basic strategies for everyday living: Keeping the home clean and tidy
|
8
|
Basic strategies for everyday living: Healthy eating and cooking
|
9
|
Basic strategies for everyday living: Doing laundry and managing medication
|
10
|
Strategies that go beyond the basics: Overview, grocery shopping and transportation
|
11
|
Strategies that go beyond the basics: Managing money
|
12
|
Strategies that go beyond the basics: Social skills, communication and leisure skills
|
13
|
Strategies that go beyond the basics: Works skills
|
14
|
Putting supports into practice
|
During the first session, the therapist gives feedback on the cognitive assessment, announces to the dyad the group they are in, and schedules the follow-up appointments. In order to improve adherence to treatment, appointments are reminded to the dyad by email one day before the scheduled appointment. Then, module 1 is sent to the dyad. A feedback of this module is done one week later. For each module, a visuo-consulting feedback is provided to the dyad with the psychologist. This feedback lasts between 15 and 20 minutes where the therapist can answer any technical questions about the environmental support, the place where it has been set up, motivational issues etc.
At the last feedback, the therapist makes sure to get feedback on the program and on the patient's progress.
Control Group
The control group receives a psycho-education manual, with a weekly reading module and a 15-minute webcam feedback by the psychologist.
- 15 sessions of the psycho-education manual
- 1 session per week sent by e-mail
- A 15-20 minutes video feedback with the psychologist (different to the psychologist who performs the last assessments)
- dyad: patient and a family member
The psycho-educational manual was created within the unit by psychologists specialized in schizophrenia and behavioral and cognitive therapies.
The choice of the modules is based on factors that can improve healthy living, such as physical activity, nutrition and limited use of toxic substances.
The interactive manual has been created to allow the formulation of SMART goals and the implementation of new behaviors to enhance improvement.
Modules Contents
1
|
Physical activity
|
2
|
Physical activity part 2
|
3
|
Eating habits
|
4
|
Eating habits part 2
|
5
|
Hydration
|
6
|
Smoking
|
7
|
Smoking part 2
|
8
|
Alcohol and drugs
|
9
|
Alcohol and drugs part 2
|
10
|
Stress and relaxation
|
11
|
Sleep
|
12
|
Sleep part 2
|
13
|
Respecting the drug treatment
|
14
|
Social relationship
|
15
|
Social relationship part 2
|
Outcomes measurements and other data collected
Primary outcome measures
- Life Skills Profile Score (LSP-39) [ Time Frame: Baseline–16 weeks – 6 months ]
The "Life Scale Profile" (LSP), validated in French by Mohr et al [41] is a scale used to assess the subject's life skills profile, particularly for patients with schizophrenia. It is a self-administered questionnaire based on the patient's functioning during the last week (excluding any acute or relapse phase). The scale is composed of 20 items. The instruction is to rate each item based on a Likert scale from 1 to 4: "always, usually, rarely and never". The lower the score, the more the patient has a deficit profile in terms of life. The maximum score is 80. The LSP scale assesses 5 dimensions of life skills: sociability, self-management, treatment compliance, antisocial behaviors and strange behaviors. The total duration of the test is about 30 minutes.
Secondary outcome measures
1. Global score of the Zarit burden interview [ Time Frame: Baseline–16 weeks – 6 months ]
Zarit's burden scale [42,43] is a 22-item self-questionnaire measuring the burden experienced by a caregiver of an individual with a chronic disorder. The total score, which is the sum of the scores obtained from the 22 items, varies from 0 to 88; a score less than or equal to 20 indicates a low or zero load; a score between 21 and 40 indicates a low load; a score between 41 and 60 indicates a moderate load; and a score greater than 60 indicates a high load.
2. Patient quality of life: S-QoL 18 [ Time Frame: Baseline–16 weeks – 6 months ]
The quality of life of patients is assessed using a French scale, the Quality of Life Scale (S-QoL 18). The S-Qol 18 is a shortened version of the S-QoL 41 [44] scale whose validity and psychometric properties have been validated in patients with schizophrenia [45]. This self-administered questionnaire assesses the impact of patients' difficulties on their quality of life through 8 dimensions: psychological well-being, self-esteem, family relationships, friendly relationships, resilience, physical well-being, autonomy and emotional life and a total score (index score). The duration of the test is 7 minutes. Dimension and index scores range from 0, indicating the lowest quality of life, to 100, the highest quality of life.
All participants (patients with schizophrenia and their family caregiver) complete this questionnaire
3. Caregiver quality of life: S-QoL 18 [ Time Frame: Baseline–16 weeks – 6 months ]
The quality of life of caregivers is assessed by the Quality of Life Scale: As for patients, we will use the Quality of Life Scale (S-QoL 18). The self-administered questionnaire assesses the impact of patients' difficulties on their quality of life through 8 dimensions: psychological well-being, self-esteem, family relationships, friendly relationships, resilience, physical well-being, autonomy and emotional life. The duration of the test is 7 minutes. Dimension and index scores range from 0, indicating the lowest quality of life, to 100, the highest quality of life.
4. Negative symptoms [ Time Frame: Baseline–16 weeks – 6 months ]
Clinical Assessment Interview for Negative symptoms (CAINS) [46]. CAINS is a recently developed tool to evaluate the two dimensions of negative symptomatology highlighted in the literature, i.e. the motivation dimension and the decreased emotional expressivity dimension. Factor analysis of the CAINS showed a 2-factor structure, a motivation-pleasure (MAP) factor consisting of 9 items (items 1–9) and an expression (EXP) factor consisting of the remaining 4 items [46,47]. The motivation-pleasure dimension score range from 0 to 36 and the expression dimension score range from 0 to 16. A composite of the two dimensions can be computed. Total scores may vary between 0 and 52, a higher score implies that the negative symptoms are significant and that they are responsible for impaired functioning.
5. Patient medication adherence [ Time Frame: Baseline–16 weeks – 6 months ]
Medication Adherence Rating Scale [48]. This scale is one of the most widely used tools to assess compliance in individuals with schizophrenia. This is a self-administered questionnaire with 10 yes/no items offering a total score from 0 (low compliance) to 10 (high compliance).
6. Depressive symptoms [ Time Frame: Baseline–16 weeks – 6 months ]
Calgary Depression Scale for Schizophrenia (CDSS) [49] translated in French [50] is a nine item clinician rated outcome measure that assesses the level of depression in people with schizophrenia. It distinguishes depressive symptoms from negative symptoms. Scores range from 0 to 27, a higher score indicating increased level of depression.
Cognitive Functioning
1. Premorbid Intellectual Quotient (IQ): fNART [Time Frame: Baseline– 6 months]
The premorbid IQ is assessed by the French National Reading Test (fNART) [51]. Based on the ability to pronounce 40 irregularly spelled words (one point per correct answer). This test provides an estimate of the participant's premorbid IQ. Scores range from 0 to 40.
2. Episodic Memory: California Verbal Learning Test (CVLT) [Time Frame: Baseline– 6 months]
The CVLT [52] was developed to evaluate in a multifactorial way verbal learning and memory. It has the particularity to quantify several cognitive components of verbal memory in only one test. Its duration is around 20 minutes. A list of 16 words (four from each of four semantic groups) is presented orally to the participants, who are required to recall the words immediately, after short, and long delays, and also with and without semantic cues. A recognition task is then administered. The test includes the following measures to reflect learning and recall, also called primary variables: Total Trial 1–5, Short Delay Free Recall (SDFR), Short Delay Cued Recall (SDCR), Long Delay Free Recall (LDFR), and Long Delay Cued Recall (LDCR). The CVLT also includes other variables that reflect processing of information and other cognitive processes such as Semantic Clustering and Serial Clustering, Region effects, Intrusions, and Perseverations.
3. Working Memory: Letter Number sequence – Wechsler Adult Intelligence Scale IV (WAIS IV) [Time Frame: Baseline– 6 months ]
Working memory is assessed using the WAIS IV letter-number sequence test [53] which is a validated measure of working memory. The purpose of the task is to locate the sequence orally by ordering the numbers in ascending order and the letters in alphabetical order. The test measures the subject's ability to retain, in the short-term information, while manipulating it mentally.
Evaluation specific for the patient, in order to determine the type of compensatory and environmental intervention:
1. Wisconsin Card Sorting Test (WCST) [Time Frame: Baseline– 6 months]
The WCST [54] is a test to study mental flexibility and abstraction skills. The subject is presented with 4 cards that differ in color of the shape of the items on each card (circles, squares, triangles, etc.) and the number of items on each card. The task is to categorize the cards. The participant is instructed to organize the cards as they wish (by color, shape or number of shapes). The examiner gives feedback (‘yes’ or ‘no’) if the chosen criterion is the right one. The participant has to adapt his behavior when the examiner decides to change the criterion. The dependent variables are: the number of well-placed cards (score ranges from 0 to 128), the number of categories achieved (score ranges from 0 to 6), the number and percentage of errors, the number and percentage of persevering errors.
2. Test of Verbal Fluency [Time Frame: Baseline– 6 months]
The test of Verbal Fluency [55] evaluates access to lexical stock as well as certain executive processes such as mental flexibility, verbal inhibition and updating in working memory. This test includes a semantic part and a lexical part. The participant in each part is asked to produce the most words in 2 minutes. In the lexical part the participant is asked to give the most words in two minutes starting with a given letter (P). In the semantic part, the participant is asked to name the largest number of words belonging to an animal category in two minutes. The dependent variables are the total number of words for each condition, the number of repetitions, and the number of errors.
3. Evaluation of behavior related to frontal functions (FrSBe) [Time Frame: Baseline– 6 months]
The Frontal Systems Behavior Scale (FrSBe) [56] comprising of 46 items, evaluates three types of behaviors associated with executive/frontal dysfunction: apathetic, disinhibited and dysexecutive behaviors. This scale is completed by the caregiver on his or her loved one suffering from schizophrenia. Three sub-scores (apathetic, disinhibited, dysexecutive) constitute the dependent variables and are obtained by summing each type of item respectively.
4. Evaluation of the CAT techniques put in place [Time Frame: each week]
An evaluation of the degree of implementation of the techniques taught in the CAT for family is made by noting both the frequency and type of CAT strategies used via a semi-structured interview [2] at each session. Two variables are noted: number of techniques used and frequency of use of each technique.
Participant Timeline
Planned Trial Calendar
Planned regulatory period: 3 months
Planned duration of recruitment: 18 months
Duration of participation of each subject: 10 months
Planned statistical analysis/valorization period: 3-6 months
Planned total trial period: 36 months
Visit schedule
Item
|
Screening
|
Baseline
|
|
Final Visit
|
|
V0
|
V 1
|
V 2
|
V 3
|
Date
|
|
Day 0 +15 days
|
4 months ±15days
|
6 months ±15days
|
Informed consent
|
X
|
|
|
|
Medical history
|
|
X
|
X
|
X
|
Treatment
|
|
X
|
X
|
X
|
Socio-demographic data
|
|
X
|
X
|
X
|
PATIENT
|
|
|
|
|
Clinical evaluation
|
|
|
|
|
PANSS
|
|
X
|
X
|
X
|
CAINS
|
|
X
|
X
|
X
|
Functional evaluation
|
|
|
|
|
CDSS
|
|
X
|
X
|
X
|
MARS
|
|
X
|
X
|
X
|
LSP
|
|
X
|
X
|
X
|
SQOL-18
|
X
|
X
|
X
|
X
|
Cognitive assessment
|
|
|
|
|
fNART
|
|
X
|
|
X
|
CVLT
|
|
X
|
|
X
|
WAIS IV ( letter-number sequence)
|
|
X
|
|
X
|
WCST
|
|
X
|
|
X
|
Verbal fluency
|
|
X
|
|
X
|
Environmental assessment
|
|
X
|
X
|
X
|
CAREGIVER
|
|
X
|
X
|
X
|
SQOL-18
|
|
X
|
X
|
X
|
ZARIT
|
|
X
|
X
|
X
|
FrSBe
|
|
X
|
X
|
X
|
Determination of sample size and power calculation
Professionally conducted cognitive remediation programs have an effect size of 0.7 [11]. In Kidd [22], where the program was family led, the observed effect sizes ranged from 0.6 to 1.09. We therefore hypothesize an effect size of 0.7 in our study. In our usual clinical practice, caregivers of patients suffering from schizophrenia are highly adherent to care. By recruiting 40 dyads per group, with 2 dyads lost to follow-up, we will be able to show an effect size of 0.75, with a power of 90%, at 5% alpha risk. The investigators contacted psychiatrists on the different psychiatric units of the hospital to present the research project. The investigators also made presentations at family association meetings and contacted private psychiatrists. Flyers were also distributed at each presentation.