Interventions Against Fatigue in Patients With Myasthenia Gravis

NCT ID: NCT06659627

Last Updated: 2025-09-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-04

Study Completion Date

2026-12-31

Brief Summary

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A prospective assessor-blinded randomized clinical trial investigating the effect of aerobic exercise therapy or cognitive behavioural therapy on fatigue in patients with myasthenia gravis.

Detailed Description

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This study will be a prospective assessor-blinded randomized controlled trial comparing AET and CBT with usual care (UC). For an individual participant, the overall study duration will be 52 weeks with a total intervention duration of 16 weeks. After 32 and 52 weeks the investigators will analyse the data from the activity tracker and approach each participant to digitally complete a total of three questionnaires. After 32 weeks the researchers will be unblinded and the study will proceed as an open-label extension study.

After signing the informed consent form, an activity tracker (Withings Pulse HR) will be provided to all participants. After a four week observation period to evaluate the baseline levels of daily activity, participants will visit the LUMC for baseline measurements and a blood test. After obtaining these baseline characteristics, all participants will be randomly assigned to either AET, CBT or UC.

Participants in the AET group start with an intake meeting with a physical therapist. AET will consist of three weekly sessions of aerobic workouts on a bicycle ergometer for a period of 16 weeks. The first training session will be supervised by an experienced physical therapist at the LUMC. Subsequently, participants will perform the remaining workouts at home. One session per week will be carried out independently at home. The other two sessions will be digitally supervised via a digital connection by students, who will be trained and supervised by an experienced physical therapist. During the intervention, training intensity will be adjusted based on the participant's rate of perceived exertion (Borg Rating of Perceived Exertion (RPE) scale). During each session, the participant is also able to adjust the wattage of that specific training. Training activity and execution will be monitored remotely using the bicycle ergometer and the activity tracker. Adherence and reasons for possible non-adherence will be monitored by the students. Outcome measures will be collected on follow-up immediately after the 16-week intervention.

Participants in the CBT group start with an online intake meeting with a psychologist. The entire CBT program will be followed digitally through an online platform and will span 12-16 weeks. The program will be tailored to the individual participants' needs and preferences. Every week or every two weeks, the psychologist provides feedback on the finished sessions and gives new assignments. If necessary, the psychologist will contact a participant by phone for additional support. Outcome measures will be collected on follow-up immediately after the 16-week intervention.

The outcome measures of the participants in the UC group are obtained after the four week observation period and after 20 weeks follow-up. Participants are not restricted in their activities, but will be instructed not to start a new exercise or cognitive behavioural program. Chronic physical therapy and psychological counselling in the context of usual care are allowed to continue. After the 32-week follow-up, the participants in the UC group have the option to follow a modified version of the AET or CBT interventions without supervision.

Participants will be given the option to undergo a quantitative muscle MRI of the upper legs. The MRI is additional and not mandatory to participate in the study. The investigators will include a maximum of 10 participants per group. Participants will undergo the MRI twice: before intervention at baseline and after intervention at 20 weeks follow-up.

Furthermore, a qualitative study will be conducted to explore the experiences of participants in both the AET and CBT groups. Semi-structured interviews, based on a topic list, will be held with 10 participants from each intervention group separately. These interviews will take place within three months after the intervention phase has ended.

Conditions

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Myasthenia Gravis Fatigue

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Three intervention groups
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Investigators Outcome Assessors
The researchers are blinded. After 32 weeks of the last patient the researchers will be unblinded and the study will proceed as an open-label extension study.

Study Groups

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Aerobic exercise therapy

AET will consist of three weekly sessions of aerobic workouts on a bicycle ergometer for a period of 16 weeks. The first training session will be supervised by an experienced physical therapist at the LUMC. Subsequently, participants will perform the remaining workouts at home. One session per week will be carried out independently at home. The other two sessions will be digitally supervised via a digital connection by students, who will be trained and supervised by an experienced physical therapist. During the intervention, training intensity will be adjusted based on the participant's rate of perceived exertion (Borg Rating of Perceived Exertion (RPE) scale).

Group Type OTHER

Aerobic exercise therapy

Intervention Type BEHAVIORAL

Participants will follow an aerobic exercise therapy program for 16 weeks.

Cognitive behavioural therapy

The entire CBT program will be followed digitally through an online platform and will span 12-16 weeks. The program will be tailored to the individual participants' needs and preferences. Every week or every two weeks, the psychologist provides feedback on the finished sessions and gives new assignments. If necessary, the psychologist will contact a participant by phone for additional support.

Group Type OTHER

Cognitive behavioural therapy

Intervention Type BEHAVIORAL

Participants will follow an cognitive behavioural therapy program for 12-16 weeks.

Usual care

Participants are not restricted in their activities, but will be instructed not to start a new exercise or cognitive behavioural program. Chronic physical therapy and psychological counselling in the context of usual care are allowed to continue.

Group Type OTHER

Usual care

Intervention Type OTHER

Participants do not follow a program, but continue with care as usual

Interventions

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Aerobic exercise therapy

Participants will follow an aerobic exercise therapy program for 16 weeks.

Intervention Type BEHAVIORAL

Cognitive behavioural therapy

Participants will follow an cognitive behavioural therapy program for 12-16 weeks.

Intervention Type BEHAVIORAL

Usual care

Participants do not follow a program, but continue with care as usual

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Age ≥ 18 years
2. A clinical diagnosis of myasthenia gravis (ocular or generalized) as defined by the Dutch national guideline (category "definite" or "probable" MG).
3. The diagnosis of MG was made at least a year ago and the MG is stable, as determined by the treating neurologist.
4. Patients who use the following medication: prednisone, intravenous immunoglobulin (IVIg), complement inhibitor (e.g. Eculizumab), neonatal Fc receptor (FcRn) inhibitor (e.g. Efgartigimod) have been on a stable dosing regimen for at least one month.
5. MGFA Clinical Classification of disease severity I-IV.
6. Clinically relevant fatigue (a score ≥ 27 on the CIS-fatigue).
7. Ability to walk and exercise.
8. Ability to understand the requirements of the study and provide written informed consent.

Exclusion Criteria

1. The patient is unable to fill out the study questionnaires or be interviewed in Dutch, or is unable to undergo the tests needed for the study, or is unable to give informed consent for participation in the study.
2. The patient is unable to use the activity tracker and digital infrastructure provided.
3. Co-morbidity interfering with AET or affecting exercise response and exercise capacity, including severe cardiopulmonary co-morbidity, as assessed by the investigator.
4. Co-morbidity interfering with CBT, a clinical diagnosis of depression or a score ≥12 on the Hospital Anxiety and Depression Scale (HADS) depression subscale, as assessed by the investigator.
5. Use of beta blockers.
6. The patient is already engaged in strenuous exercise more than twice a week.
7. The patient is already undergoing cognitive behavioural therapy.
8. Pregnancy or intention to become pregnant during the study.

Exclusion Criterion for muscle MRI 1. Inability to undergo MRI.

\- In case of uncertainty about the MRI-contraindications, the MR-safety commission of the Radiology department will decide whether this subject can be included in the study or not.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Leiden University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Martijn R. Tannemaat, MD PhD

Principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Martijn R. Tannemaat, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

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Leiden University Medical Center

Leiden, South Holland, Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Martijn R Tannemaat, MD, PhD

Role: CONTACT

+31715262197

Yvonne JM Campman, MD

Role: CONTACT

+31715262118

Facility Contacts

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Martijn R. Tannemaat, MD, PhD

Role: primary

+31 71 5262197

Other Identifiers

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NL85072.058.23

Identifier Type: -

Identifier Source: org_study_id

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