The Effectiveness of an ETP Programme in Myasthenia Gravis: a Proof-of-concept Study.

Official title

Efficacité d'un Programme d'ETP Dans la myasthénie : étude de Preuve de Principe (MY-EDUC).

Overview

CONTEXTE. Myasthenia gravis is a rare neuromuscular junction disorder affecting one in five thousand people (ORPHA 589). It is a chronic condition that progresses in episodes. Its severity varies, ranging from the invisible disability of fatigue to respiratory distress requiring intensive care. Currently, 270 patients with myasthenia gravis are being treated at Grenoble University Hospital in the Reference Centre for Rare Neuromuscular Diseases. The impact of this disease on quality of life is significant, and medication alone is not sufficient. However, to date, there are virtually no psychosocial interventions for patients with myasthenia gravis and no studies evaluating their effectiveness. In this context, the Cognitive Behavioural Stress Management (CBSM) programme is one of the stress management programmes applied to chronic health conditions whose effectiveness has already been demonstrated, particularly in terms of treatment adherence, quality of life, patients' coping strategies in the face of a chronic illness, and the outcomes of medical treatments (Antoni, 2003; Antoni et al., 2002, 2006). PRIMARY OBJECTIVE. Evaluation of the adaptation of an existing patient education programme, 'Living Better with Myasthenia', following the inclusion of an eight-session CBSM-based stress management module for adult patients living with myasthenia. METHODOLOGY (brief). Adaptation of the CBSM programme to the specific characteristics of myasthenia gravis: 1. Focus groups: exploration of beliefs associated with stress in myasthenia gravis. 2. DELPHI group: validation of the adaptation of the ETP programme 'Living better with myasthenia gravis' implemented at CHUGA following the inclusion of a stress management module (CBSM). Assessment of the feasibility of the MY-EDUC programme among groups of patients with myasthenia gravis. PRIMARY OUTCOME MEASURE. Comparison of levels of anxiety, depression (HADS), perceived stress (PSS) and quality of life (SF-36) as self-reported by patients enrolled in the programme before and after the MY-EDUC intervention. RESEARCH PROCEDURE. 1.1. FOCUS GROUPS. Expert patients and partner patients. They will be contacted via the list maintained by the rare disease healthcare network. 'General public' patients. A call for participants will be displayed in the CHUGA waiting room and circulated by partner organisations to their members. The study will be presented to expert and partner patients, as well as to "walk-in" patients in the focus groups, using the contact details on the "rare disease healthcare network" lists and via posters. An information leaflet outlining the study and its objectives will be provided to them. 1.2. FEASIBILITY AND ACCEPTABILITY STUDY OF THE MY-EDUC PROGRAMME. 1.2.1. Participant inclusion. Patient eligibility. The assessment of patient eligibility will be carried out by a specialist doctor from the CHUGA Rare Disease Centre of Excellence during a routine consultation with the patient (routine care). Participant inclusion. Once patient eligibility has been verified, the investigator from the CHUGA Rare Disease Centre, or a person to whom they have delegated this task, will contact the patient to invite them to participate in the MY-EDUC study. They will provide a verbal explanation of the study and hand over an information sheet during a follow-up consultation with the patient as part of routine care. If the patient volunteers to participate, they will give their consent to participate. The patient's consent will be recorded in the medical record. 1.2.2. Baseline assessment (T0). In the week leading up to the first session of the MY-EDUC programme, participants will complete the baseline assessment online (using the LimeSurvey platform - secure servers at the University of Grenoble Alpes) with questionnaires presented in a randomised order. 1.2.3. Assessment during the intervention (T1). Based on repeated ecological measurements (Shiffman et al., 2008) via the study participants' mobile phones (two measurement points, before and after each session, randomly scheduled at least 36 hours apart, i.e. 16 measurements) using the free PielsSurvey software. 1.2.4. Final assessments (T2 and T3). Within one week of the final session of the MY-EDUC programme (T2: week 10 after T0), participants will complete a set of questionnaires electronically (using the LimeSurvey platform - secure servers at the University of Grenoble Alpes), with the validated questionnaires presented in a randomised order.

Detailed description

1. Background and Rationale Myasthenia Gravis (MG) is a rare autoimmune disorder of the neuromuscular junction (ORPHA 589), characterised by its chronic nature and the occurrence of fluctuating symptoms or flare-ups. Beyond the physical manifestations, the condition has a major impact on patients' quality of life. Recent data suggest that approximately 46.3% of patients suffer from anxiety disorders. While a Therapeutic Patient Education (TPE) programme entitled "Living better with myasthenia" is already established at Grenoble University Hospital, patients have expressed a clear requirement for specific modules addressing stress and anxiety management.

The MY-EDUC programme aims to adapt the current TPE framework by integrating a stress management module based on Cognitive Behavioural Stress Management (CBSM). CBSM has proven effectiveness in various chronic pathologies for improving treatment adherence, quality of life, and coping strategies. 2. Objectives Primary Objective: To evaluate the adaptation of the existing TPE programme after incorporating a CBSM-based stress management module (8 sessions) for adult patients with myasthenia gravis.

Secondary Objectives: To assess the feasibility and acceptability of the MY-EDUC programme. 3. Study Design and Methodology

This is an observational, prospective, descriptive, and monocentric study (classified as RIPH3 under French regulations). The research is conducted in three phases:

Phase 1 (Focus Groups): Exploration of stress-related beliefs with both expert patients and regular patients to adapt the session content.

Phase 2 (Feasibility Study): Implementation of the programme with 40 patients (organised into 5 groups of 8 participants maximum). 4. Description of the Intervention (MY-EDUC) The programme consists of 8 weekly sessions. It combines transversal stress management modules with modules specifically tailored to myasthenia. The approach is modular and transdiagnostic, designed to facilitate future national rollout within the FILNEMUS network. 5. Outcome Measures and Assessments Assessments are performed electronically (via LimeSurvey) at several intervals: T0 (baseline), T1 (during the intervention via repeated ecological momentary assessments on smartphones), T2 (post-intervention), and T3 (1-month follow-up).

Psychological Measures: Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS), and Brief COPE.

Quality of Life: 36-Item Short Form Survey (SF-36).

Ecological Assessments: Evaluation of stress and anxiety levels before and after each session (16 measurement points via PielsSurvey). 6. Statistical Analysis Plan

Data analysis will include:

Descriptive statistics of the population's demographic and medical characteristics.

Analysis of Covariance (ANCOVA) to compare means between groups at different time points.

Repeated measures Analysis of Variance (ANOVA) to evaluate the sustainability of the effects.

Multivariate linear regressions and network analyses to explore interactions between variables and identify subgroups of responders to the intervention. 7. Expected Results The study intends to demonstrate that a TPE programme enhanced by a cognitive-behavioural approach reduces anxiety and depression while improving pain management and overall quality of life. Ultimately, this modular model could be transposed to other rare diseases, such as Amyotrophic Lateral Sclerosis (ALS).

Interventions

• Behavioral CBSM
  Cognitive Behavioural Stress Management (CBSM) is a structured, multimodal psychological intervention based on the transactional model of stress. It addresses the distress arising from the perceived imbalance between disease-related threats and available coping resources. CBSM aims to disrupt the cycle of physical symptoms and psychological strain. The intervention integrates several core evidence-based techniques: Cognitive Restructuring: Identifying and challenging dysfunctional thoughts rel

Primary outcome measures

• Perceived stress [Time frame: T0: Initial assessment at least 7 days before intervention. T2: After intervention assessment (maximum 7 days after intervention). 73: Maintenance effect (4 weeks after the end of the intervention).]
• Anxiety [Time frame: T0: Initial assessment at least 7 days before intervention. T2: After intervention assessment (maximum 7 days after intervention). 73: Maintenance effect (4 weeks after the end of the intervention).]
• Depression [Time frame: T0: Initial assessment at least 7 days before intervention. T2: After intervention assessment (maximum 7 days after intervention). 73: Maintenance effect (4 weeks after the end of the intervention).]

Secondary outcome measures (1)

• Health-related Quality of Life [Time frame: T0: Initial assessment at least 7 days before intervention. T2: After intervention assessment (maximum 7 days after intervention). 73: Maintenance effect (4 weeks after the end of the intervention).]

Eligibility criteria

Inclusion criteria

• Participant is aged 18 years or over (legal age of majority under French law).
• Participant has freely provided their non-opposition to participate in the study.
• Participant has a confirmed diagnosis of Myasthenia Gravis.
• Participant has sufficient proficiency in both spoken and written French to complete assessments and questionnaires, attend the programme sessions, and carry out home-based exercises.

Exclusion criteria

• Participant presenting with one or more severe and established psychiatric disorders (e.g. severe depression, psychosis) that could interfere with the study's conduct, particularly the assessment of the primary and secondary endpoints.
• Participant presenting with another chronic condition that induces fatigue. Protected persons (as defined by Articles L1121-5 to L1121-8 of the French Public Health Code \[CSP\]).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Shiffman S, Stone AA, Hufford MR. Ecological momentary assessment. Annu Rev Clin Psychol. 2008;4:1-32. doi: 10.1146/annurev.clinpsy.3.022806.091415. PMID 18509902
• Roy-Byrne PP, Davidson KW, Kessler RC, Asmundson GJ, Goodwin RD, Kubzansky L, Lydiard RB, Massie MJ, Katon W, Laden SK, Stein MB. Anxiety disorders and comorbid medical illness. Gen Hosp Psychiatry. 2008 May-Jun;30(3):208-25. doi: 10.1016/j.genhosppsych.2007.12.006. PMID 18433653
• Philippot, P., Bouvard, M., Baeyens, C., & Dethier, V. (2015). Vers un protocole de traitement processuel et modulaire des troubles anxio- dépressifs. Journal de Thérapie Comportementale et Cognitive, 25(3), 106-116. https://doi.org/10.1016/j.jtcc.2015.07.001
• Farchione TJ, Fairholme CP, Ellard KK, Boisseau CL, Thompson-Hollands J, Carl JR, Gallagher MW, Barlow DH. Unified protocol for transdiagnostic treatment of emotional disorders: a randomized controlled trial. Behav Ther. 2012 Sep;43(3):666-78. doi: 10.1016/j.beth.2012.01.001. Epub 2012 Jan 18. PMID 22697453
• Chorpita BF, Weisz JR, Daleiden EL, Schoenwald SK, Palinkas LA, Miranda J, Higa-McMillan CK, Nakamura BJ, Austin AA, Borntrager CF, Ward A, Wells KC, Gibbons RD; Research Network on Youth Mental Health. Long-term outcomes for the Child STEPs randomized effectiveness trial: a comparison of modular and standard treatment designs with usual care. J Consult Clin Psychol. 2013 Dec;81(6):999-1009. doi: PMID 23978169
• Chen S, Forster S, Yang J, Yu F, Jiao L, Gates J, Wang Z, Liu H, Chen Q, Geldsetzer P, Wu P, Wang C, McMahon S, Barnighausen T, Adam M. Animated, video entertainment-education to improve vaccine confidence globally during the COVID-19 pandemic: an online randomized controlled experiment with 24,000 participants. Trials. 2022 Feb 19;23(1):161. doi: 10.1186/s13063-022-06067-5. PMID 35183238
• Carver CS. You want to measure coping but your protocol's too long: consider the brief COPE. Int J Behav Med. 1997;4(1):92-100. doi: 10.1207/s15327558ijbm0401_6. PMID 16250744
• Antoni MH, Wimberly SR, Lechner SC, Kazi A, Sifre T, Urcuyo KR, Phillips K, Smith RG, Petronis VM, Guellati S, Wells KA, Blomberg B, Carver CS. Reduction of cancer-specific thought intrusions and anxiety symptoms with a stress management intervention among women undergoing treatment for breast cancer. Am J Psychiatry. 2006 Oct;163(10):1791-7. doi: 10.1176/ajp.2006.163.10.1791. PMID 17012691

Identifiers

NCT: NCT07512375 · 38RC25.0025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗