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Behavior Cognitive Therapy on Fatigue Impact in MS Patients

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ClinicalTrials.gov Identifier: NCT03758820
Recruitment Status : Recruiting
First Posted : November 29, 2018
Last Update Posted : November 29, 2018
Sponsor:
Information provided by (Responsible Party):
Réseau Sep Idf Ouest

Tracking Information
First Submitted Date  ICMJE October 19, 2017
First Posted Date  ICMJE November 29, 2018
Last Update Posted Date November 29, 2018
Actual Study Start Date  ICMJE May 31, 2017
Estimated Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 28, 2018)
Change assessment from Baseline measure of Fatigue Impact to month 6, 12 and 18 [ Time Frame: After 6 weeks and 6,12 and 18 months ]
Fatigue impact evaluated by MFIS autoquestionnaire MFIS : Modified Fatigue Impact Scale, 5 response option (0 to 4), score of between 0 (better) and 84 (worse) : A score > 45 means the patient is affected by fatigue.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 28, 2018)
  • Change assessment from Baseline of Anxiety and depression [ Time Frame: After 12 months ]
    Anxiety and depression evaluated by HADS autoquestionnaire HADS : Hospital Anxiety and Depression Scale, five-point rating scale (0 to 4), score of between 0 (better) and 42 (worse).
  • Change assessment from Baseline of Fatigue severity [ Time Frame: After 6 weeks and 6 and 12 months ]
    Fatigue severity evaluated by FSS autoquestionnaire FSS : Fatigue Severity Scale, seven-point rating scale (1 to 7), score >3 = fatigue severity
  • Change assessment from Baseline of Quality of sleep: Pittsburgh Sleep Quality scale [ Time Frame: After 12 months ]
    Quality of sleep evaluated by Pittsburgh scale. IQSP 1.0 : Pittsburgh Sleep Quality scale, four-point rating scale (0 to 3), score of between 0 (better) and 21 (worse) : score >5 = sleep disorder.
  • Change assessment from Baseline of Quality of sleep: Epworth Sleepiness Scale [ Time Frame: After 12 months ]
    Quality of sleep evaluated by Epsworth scale. Epworth Sleepiness Scale : four-point rating scale (0 to 3), score of between 0 (better) and 24 (worse) : score >9 = risk of pathological somnolence
  • Change assessment from Baseline of Cognitive disorders [ Time Frame: After 12 months ]
    Cognitive disorders evaluated by PASAT. PASAT : Paced Auditory Serial Addition Test de Gronwall. Score of between 0 (worse) and 60 (better).
  • Change assessment from Baseline of Cognitive disorders [ Time Frame: After 12 months ]
    Cognitive disorders evaluated by CSCT. CSCT : Computerized speed cognitive test. The score is the number of correct answer provided in 90 seconds. At the end of each test, the patient's score is automatically interpreted according to the normative values for his age, level of education and sex. If a patient's score is less than 1.5 SD of normal values, it is likely that this patient has a TTI slowing.
  • Change assessment from Baseline of Quality of life: MSIS-29 [ Time Frame: After 6,12 and 18 months ]
    Quality of life evaluated by MSIS-29. MSIS-29 : The Multiple Sclerosis Impact Scale. 29-item self-report measure with 20 items associated with a physical scale and 9 items with a psychological scale. 5 response options (1 to 5). Each of the two scales are scored by summing the responses across items, then converting to a 0-100 scale where 100 indicates greater impact of disease on daily function (worse health).
  • Change assessment from Baseline of Quality of life: EQ5D-3L [ Time Frame: After 6,12 and 18 months ]
    Quality of life evaluated by EQ5D-3L. EQ5D-3L European Quality of Life. Five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
  • Change assessment from Baseline of Medical care consumption and professional impact [ Time Frame: After 6,12 and 18 months ]
    Medical care consumption evaluated by the number of visits to the physician, treatment and hospitalization
  • Change assessment from Baseline of professional impact [ Time Frame: After 6,12 and 18 months ]
    professional impact evaluated by the number of work stoppage
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Behavior Cognitive Therapy on Fatigue Impact in MS Patients
Official Title  ICMJE Multicenter Study, Randomized, Parallel Group Controlled, Testing the Effectiveness of a Behavioral Cognitive Therapy (BCT) vs Usual Local Practice on the Fatigue of Patients With Relapsing Remittent Multiple Sclerosis (RRMS)
Brief Summary

Multiple sclerosis (MS) is a chronic inflammatory disease that leads to demyelination of the central nervous system. Fatigue is one of the most frequent and most disabling symptoms of MS. Up to 86% of individuals with MS experience fatigue at any one time; 65% consider it to be one of their three most troubling symptoms. Fatigue may limit or prevent participation in dayly activities and reduce psychological well-being (1, 2). Pharmacological and non-pharmacological treatments are available for MS-related fatigue, but evidence on effectiveness is mostly inconclusive or non-existent. The psychological approaches of fatigue management are interesting. To date, three RCTs using cognitive-behavioral group-based approaches in MS fatigue management programs have demonstrated their effectiveness (3-6). The results demonstrated a reduction in fatigue scores and better self-management of the disease in general. However, if these programs are effective at the time of their application and in the medium term, the issue of maintaining long-term therapeutic benefits is problematic.

The aim of this research is to assess the effectiveness of the FACETS program (6), on a population of French patients with RRMS over a 18 month period. This program focuses on the management of fatigue and is based on a conceptual framework that incorporates elements of cognitive-behavioral, self-efficacy, self-management and energy effectiveness theories. It consists of six once-weekly sessions of 90 minutes, with homework activities between the sessions. It is designed for groups of 6 to 10 people. The investigators propose to add 4 booster sessions to the FACETS program, at week 6, 12, 18 et 36 after the end of the program, in order to activate and reinforce the cognitive and behavioral processes and enhance the benefits of FACETS in the longer term.

This trial is randomized controlled comparative comparing a group receiving a FACETS program with a group receiving only a current local practice. Socio-demographic and medical data are measured as well as fatigue impact, fatigue severity, anxiety and depression, sleep disorder and quality of life.

The expected results are a significantly greater decrease in fatigue severity and impact in the FACETS group than the control group post intervention and this difference will be maintained at 1 year.

Detailed Description

In spite of the fatigue impact is well known in MS, medical care of this symptom is not usual. Moreover, treatments of fatigue are available, but evidence for effectiveness is limited. This study will build upon the existing evidence base for the effectiveness of cognitive behavioral approaches, and particularly the recent FACETS trial published by co-applicants.

Scientific aim is to assess the effectiveness of the FACETS program plus 4 additional booster sessions on a population of French patients with RRMS over a 12 months period.

This study will provide evidence on whether the FACETS program plus booster sessions is effective in helping MS patients with their fatigue. The program is designed to facilitate use within health services. Thus, if the results from this trial are positive, there is potential for directly adding to the treatment options available to MS patients who have troublesome fatigue, and improving the central nervous system affecting approximately 2.5 million people (5). Fatigue is one of the most commonly reported and disabling symptoms of MS, often occurring daily (6) and with a variable course (7-8). Up to 86% of individuals with MS experience fatigue at any one time; 65% consider it to be one of their three most troubling symptoms. Fatigue has been defined as a "subjective lack of physical and/or mental energy that is perceived by the individual or caregiver to interfere with usual or desired activities" (9).

Researchers have distinguished between primary and secondary fatigue (10). "Primary" fatigue relates to aspects of fatigue deemed to be directly related to the disease process such as lassitude or asthenia (an overwhelming sense of tiredness not directly related to participation in activity or exercise), "short-circuiting" fatigue (when muscular performance deteriorates during sustained activity but recovers after a short rest break) and heat sensitive fatigue (where fatigue is triggered or worsened by heat). "Secondary" fatigue refers to fatigue that is not unique to MS and is related to factors common to a range of chronic and disabling conditions (e.g. sleep disturbance, medication side effects, infection, physical exertion, depression, anxiety, stressful life events, characteristics of the local environment - such as lighting and temperature within a work setting). The relationship between these dimensions is complex; various symptoms of MS may act as predisposing factors for secondary fatigue.

Fatigue may limit or prevent participation in everyday activities, work, leisure and social pursuits, restrict role fulfilment and reduce psychological well-being (1-2) and is one of the key precipitants of early retirement (11-12). Its 'invisible' nature may lead to difficulties in personal and work relationships (13-14).

Although fatigue is one of the major symptoms of MS patients, the pathophysiology of fatigue is unclear (15) but likely to be multi- factorial (16-17). Findings on the relationships between fatigue and other clinical variables (such as age, gender, disease duration, and clinical activity) have been equivocal (18). The neural correlates are poorly components such as peripheral vs. central fatigue or physical vs. cognitive or mental, which are difficult to define or operationalize.

Pharmacological and non-pharmacological treatments are available for MS-related fatigue, but evidence on effectiveness is mostly inconclusive or non-existent (19-20). Non-pharmacological studies exploring the effectiveness of energy conservation programs for MS-fatigue have tended to be small and uncontrolled (21-22). Although the important relationships between physical and psychological aspects of MS-fatigue are recognized, high quality randomized and controlled trials (RCTs) of psychological interventions are rare (23).

The integration of cognitive-behavioral approaches in fatigue management programs is interesting. Indeed, their effectiveness has been demonstrated in Chronic Fatigue Syndrome. To date, three RCTs using cognitive-behavioral group-based approaches in the context of MS have been conducted (3-4). Cognitive behavioral approaches are potentially more profitable than the dual interventions, more easily integrated into a framework of routine care, and they also offer the possibility of peer support. The results of these studies demonstrated a reduction in fatigue scores and better self-management of the disease in general, resulting in improvements in quality of life. In their meta-analysis (24) indicate that the results obtained with CBT or with physical exercises are similar, but when people are anxious or depressed, which is often the case with MS (25-26), CBT shows better improvement. Knoop & al. (27) highlighted the importance of cognitive representations on fatigue and the potential relevance of CBT: they showed that the strongest mediators of fatigue severity were fatigue avoidance, symptom focusing and the belief that fatigue symptoms are a sign of damage.

Thomas et al., (4) found that modest effects on fatigue severity were largely maintained at one year (unpublished data). Given that MS typically is diagnosed during the most productive years of individuals' lives and lasts the life course it is important to give people flexible tools and strategies to manage fatigue that can be used in the long term. Booster session might therefore help to 'boost' or enhance the effectiveness of the program in the longer term Methodology A multicentre parallel arm randomized controlled trial comparing a group receiving 'enhanced' FACETS plus current usual practice versus a group receiving current local practice only.

Inclusion criteria: clinically confirmed diagnosis of relapsing remitting MS; Significant fatigue levels (score at the Modified Fatigue Impact Scale - MFIS > 45); Expanded Disability Status Scale score < 6; age ≥ 18 years; written informed consent; speak and understand French; be able to follow the program.

Exclusion criteria: Individuals with cognitive deficits such that they would not be able to engage and benefit from this group-based program. Indeed, if individuals have significant cognitive deficits, most of the content of the fatigue management program would not be appropriate; People who have had a relapse within the past three months: (a relapse might result in increased fatigue) People who have started treatment on a disease modifying drug or anti-depressant in the past 3 months (one of the possible initial side effects of these drugs is fatigue); People who have psychiatric disorders Sample size: if one uses the results of the study (30) (matched groups), these authors show that in 59 MS patients treated with Modafinil, the mean fatigue score on the MFIS is 52.3 (SD/SE = 18.5), whilst in 56 MS patients treated by placebo the mean fatigue score is 49.2 (SD/SE = 16.6). The investigators will seek to uncover an absolute difference of 10 points between mean scores. The FACETS trial found a standardized effect size of 0.35 on their fatigue severity primary outcome, which would translate to around 6 points on the MFIS. It is anticipated that by using booster sessions and by running the programme using psychologists, that the anticipated effect size will be larger (10 points). In order to detect a 10 points absolute difference between the mean scores (on the MFIS) of the efficaciousness of the cognitive-behavioral intervention, power to detect an effect size of 8.5 points Participants will be identified and recruited by the neurologists of the hospitals who take part in the program, when they come for a medical examination.

Randomization: After giving their informed consent, the patients will be entered onto the trial database and randomized in a 1:1 ratio to either the fatigue management program and or current local practice using a computer, generated randomization sequence stratified by site.

Intervention FACETS (4). Focuses on the management of fatigue and is based on a conceptual framework that incorporates elements of cognitive-behavioral, self-efficacy, self-management and energy effectiveness theories. It consists of six once-weekly sessions of 90 minutes (with a break), with homework activities between the sessions. It is designed for groups of 8 to 10 people and will be delivered by two psychologists. The program is standardized: PowerPoints presentations support each session and a detailed facilitator manual and companion patient workbook. accompany the program.

The investigators propose to add 4 booster sessions to the FACETS program, at week 6, 12 et 18 et 36 after the end of the program, in order to activate and reinforce the cognitive and behavioral processes and they hope to enhance the benefits of FACETS in the longer term.

Measures For the FACETs group these will be administered pre, post and 12 months after the end of the FACETS program and at the same times for those in the control group Socio-demographic and medical data: age, sex, level of education, marital status, number of children and professional status; date of diagnosis, disease type, level of disability.

Neuropsychological measures: Paced Auditory Serial Addition Task (PASAT,28) & the Computerized Speed Cognitive Test (CSCT,29).

Statistical analysis: They will register the trial and endeavor to publish the full trial protocol prior to its commencement. The primary analysis of effectiveness will use an "intention-to-treat" approach and focus on comparing MFIS at 12 months post treatment (ie after the program and all booster sessions are complete) between the two trial arms using analysis of covariance to take into account MFIS at baseline, and study center. In addition to these analyses they will conduct further comparative analyses using a mixed model approach that permits analysis of repeated measures (baseline, post treatment and 12 months follow-up), takes into account missing data (i.e. model allows participants to contribute to the model even if they don't have complete data), and takes into account the group-based nature of the program (cluster effects). A similar approach will be used for other interval scaled outcome measures, and adapted if the outcome measure is nominal (eg the EDSS) Hypotheses There will be a significantly greater decrease in fatigue severity and impact in the FACETS group than the control group post intervention and this difference will be maintained at 1 year.

There will be a significantly greater improvement in sleepiness and sleep quality, anxiety, depression, stress, attention and working memory in the FACETS group than the control group at the end of the program and at 12 months The FACETS group will show a significantly greater reduction in cortical atrophy, axonal loss and demyelination within white matter tracts of DMN than those in the control group Ethics The protocol was submitted to the French competent authorities and a declaration was made to the CNIL.

Patients allocated to the control group (current local practice) will be offered the FACETS program after the 12 months follow-up.

Finally, all information collected will be strictly confidential. Identification numbers of participants will be noted on the questionnaires which will not contain any names or details to identify the participants. Only members of the research team will be allowed to access the trial data.

Study Type  ICMJE Interventional
Study Phase Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
parallel group assignment
Masking: Single (Participant)
Masking Description:
randomization of patients
Primary Purpose: Supportive Care
Condition  ICMJE
  • Relapsing Remitting Multiple Sclerosis
  • Fatigue
  • Cognitive Therapy
Intervention  ICMJE Behavioral: Behavorial Cognitive Therapy (BCT)

Check-in : review of the homewok Talk : Presentation of the aim of the session Group Activity : Relaxation and Execises Refreshment break Homework : exercises to practice at home and explanation about the forms to fill in.

Passout : session handbook and supports for exercises.

Study Arms
  • Experimental: BCT group

    Intervention : Behavorial Cognitive Therapy (BCT) will be delivered by two psychologists at six once-weekly sessions of 90 minutes (with homework activities between the sessions) + 4 booster sessions at week 6, 12, 18 and 36 after the end of the programme.

    It was designed for groups of 8 to 10 people. The programme is standardised: PowerPoints presentations support each session and a detailed facilitator manual and companion patient workbook. accompany the programme.

    Intervention: Behavioral: Behavorial Cognitive Therapy (BCT)
  • No Intervention: Control group
    Usual local practice
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 28, 2018)
110
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date September 2020
Estimated Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • RRMS
  • EDSS ≤ 5,5
  • MFIS score > 45
  • Outpatient treatment
  • Enable to follow the BCT sessions
  • French understanding
  • More than 18 years old
  • Inform consent signature
  • Membership in a social protection

Exclusion criteria

  • Cognitive disorders avoiding patient participation
  • Relapse within last 3 months before baseline
  • Onset of DMT within 3 months
  • Onset of antidepressive treatment within 3 months
  • Onset of treatment for fatigue within 3 months
  • Psychiatric disorders
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: Marie BLANCHERE, PhD +33.6.18.95.03.62 marie.blanchere@gmail.com
Contact: Fanny CASSEDANNE +33.6.82.39.87.86 fannycassedanne@gmail.com
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03758820
Other Study ID Numbers  ICMJE FACCSEP
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Réseau Sep Idf Ouest
Study Sponsor  ICMJE Réseau Sep Idf Ouest
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Olivier HEINZLEF, MD Réseau Sep Idf Ouest
PRS Account Réseau Sep Idf Ouest
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP