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Myasthenia Gravis (MG) is a chronic autoimmune neurological disorder where an antibody attack of muscle receptors causes fatigable skeletal muscle weakness. In addition to fatigue, several MG patients experience general fatigue. Small supervised studies during 12 weeks of physical exercise interventions have indicated safety and beneficial neuromuscular outcomes in MG patients. Longer and unsupervised studies are required to obtain guidelines for physical activity in MG patients. Further, the development of smart rings enables remote digital supervision of physical activity, sleep, and biological parameters such as heart frequency, number of steps, and temperature. These parameters could add to the lack of biomarkers in MG. The project design is a randomized controlled trial with a lifestyle intervention to improve fatigue in the autoimmune neuromuscular disease Myasthenia Gravis (MG). The intervention includes digital group counseling regarding physical activity, sleep, general health, and digital follow-up with a "smart ring" (OURA).
The cohort is Myasthenia Gravis (MG) patients in Sweden. The primary research question is: can digital lifestyle intervention in an online-group format improve fatigue as measured by MG-ADL in MG patients by at least 30%? Secondary research question: can lifestyle intervention improve fatigue as measured by FSS in MG by at least 30%?
The primary outcome measure is MG-ADL; the secondary outcome measures include general fatigue (fatigue severity scale and Chalder´s fatigue scale). Exploratory outcome measures include OURA-ring-based markers, including heart rate variability, temperature fluctuations, and sleep and activity parameters. These will be collected throughout the entire study period for 30 weeks.
Analysis of serum biomarkers miR-150-5p and miR-30e-5p and inflammatory proteins found upregulated in MG will be included. Clinical data at baseline: antibody status, electrophysiology, MG Composite Scale (MGC), and clinical data at follow-up visits (medications, MGC), etc., are extracted from the medical charts and the Swedish MG registry
Inclusion criteria:
Exclusion criteria:
Each participant is enrolled in the study for 7 months, and 26 persons are randomized to one of the following 3 groups:
The study is digital and will use the platform "minforskning.se", which is validated according to GCP-GAMP5 and has the potential to collect digital consent forms.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Observation | No Intervention | Observation with the OURA ring and no digital meetings. The participants are offered delayed randomization after the study period. This group's outcome from the delayed randomization will be for the exploratory analysis, i.e., not in the primary analysis. | |
| Physical activity | Experimental | 12 weeks of physical activity guidance with short discussions via online group meetings according to a schedule. The participants in this arm will conduct moderate-intensity exercises for at least 150 minutes per week. Brisk walks are the primary choice of activity; alternatively, swimming, cycling, or dancing to the physical exertion according to the Borg scale can be performed. |
|
| Sleep hygiene intervention | Active Comparator | 12 weeks of sleep exercises. The lifestyle intervention of sleep will be delivered via an online group, with recommended home practices between sessions. Topics covered will include sleep education, sleep hygiene, and practices to improve sleep quality. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Physical activity | Behavioral | Intervention with physical activity more than 150 minutes of medium to high intensity per week. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Myasthenia Gravis-Activities of Daily Living (MG-ADL) | Subjective assessment of MG-related fatiguability. A person's score can range from zero (normal) to 24 (most severe). | 7 months |
| Measure | Description | Time Frame |
|---|---|---|
| Fatigue Severity Scale (FSS) | The Fatigue Severity Scale (FSS) ranges from 0 (least fatigue) to 63 (maximum fatigue). | 7 months |
| Chalder Fatigue Scale | The Chalder Fatigue Scale ranges from 0 (least fatigue) to 33 (maximum fatigue) |
| Measure | Description | Time Frame |
|---|---|---|
| Heart rate variability | Heart rate variability is measured with the OURA ring. | 7 months |
| Activity pattern | Number of steps and minutes in moderate and high intensity activity is measured by the OURA ring. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anna Rostedt Punga, MD, PhD | Uppsala University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Uppsala University | Uppsala | 75185 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40675736 | Derived | Bhandage AK, Chen J, Kaminski HJ, Punga AR. Blood and digital biomarkers in MG. Int Rev Neurobiol. 2025;182:205-226. doi: 10.1016/bs.irn.2025.04.030. Epub 2025 May 9. |
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| ID | Term |
|---|---|
| D009157 | Myasthenia Gravis |
| D005221 | Fatigue |
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D020361 | Paraneoplastic Syndromes, Nervous System |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D015444 | Exercise |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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Prospective, randomized controlled trial, parallel-group design
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The statistician responsible for the outcome analysis will be blinded as to what intervention each group has had.
| Sleep hygiene | Behavioral | Intervention with sleep hygiene to optimize sleep duration and quality. |
|
| 7 months |
| 7 months |
| Percentage of deep sleep | The OURA ring measures the sleep stages, including time and percentage for deep sleep every night. | 7 months |
| Circulating miRNA in serum | Changes in miR-150-5p and miR-30e-5p in serum samples. | 7 months |
| Olink Target 96 Inflammation panel of cytokines | Changes in cytokine NPX protein values (log2 scaled) using Proximity Extension Assay (PEA) technology in serum samples | 7 months |
| D010257 | Paraneoplastic Syndromes |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D019636 | Neurodegenerative Diseases |
| D020511 | Neuromuscular Junction Diseases |
| D009468 | Neuromuscular Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001519 | Behavior |