Digital Phenotyping and Lifestyle Intervention in Patients With Myasthenia Gravis (DIG-MG)

Randomized Controlled Trial: Digital Phenotyping and Lifestyle Intervention in Patients With Myasthenia Gravis to Reduce Fatigue

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).

Study Overview

• Status: Recruiting
• Conditions: Myasthenia Gravis
• Intervention / Treatment: Behavioral: Physical activity; Behavioral: Sleep hygiene

Detailed Description

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:

• An MG diagnosis for at least six months before entry into the study.
• Both patients with ocular and generalized MG are allowed to participate.
• For practical reasons, participants need to understand Swedish.

Exclusion criteria:

• Participation in another clinical trial in the past 6 months.
• Disease duration less than 6 months.
• Contraindications to physical activity: unstable coronary syndrome or myocardial infarction within the preceding three months, respiratory failure (vital capacity < 70% predicted value) or cardiac failure (ejection fraction < 50% predicted value), concomitant neuromuscular diseases, disabling rheumatological disease (> 80% disability on the Barthel scale), chronic pain or disabling orthopedic conditions, hospitalization in the last three months for a serious medical or surgical condition, anemia (hematocrit < 30%), stroke within the previous year.
• MG patients already performing a moderate-intensity physical activity of 150min or more per week, i.e., one of the target interventions.
• Pregnancy.

Each participant is enrolled in the study for 7 months, and 26 persons are randomized to one of the following 3 groups:

• Group 1; no intervention, observation with the OURA ring.
• Group 2: 12 weeks of physical activity guidance with short discussions via digital meetings regularly. They will conduct at least 150 minutes per week of moderate-intensity exercises. 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.
• Group 3: 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.

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anna Rostedt Punga, MD, PhD; Phone Number: +46-18-4714941; Email: anna.rostedt.punga@uu.se
• Study Contact Backup: Name: Maja Norling, BSc; Phone Number: +46-18-6110000; Email: maja.norling@akademiska.se

Study Locations

• Sweden
  • Uppsala, Sweden, 75185
    • Recruiting
    • Uppsala University
    • Contact: Anna Rostedt Punga, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The MG disease status must be stable for at least six months before entry into the study; thus, the duration of the disease must be at least six months.
• Both patients with ocular and generalized MG are allowed to participate.
• For practical reasons, participants need to be able to understand fully and communicate in Swedish.

Exclusion Criteria:

• Participation in another clinical trial in the past 6 months.
• Disease duration less than 6 months.
• Contraindications to physical activity: unstable coronary syndrome or myocardial infarction within the preceding three months, respiratory failure (vital capacity < 70% predicted value) or cardiac failure (ejection fraction < 50% predicted value), concomitant neuromuscular diseases, disabling rheumatological disease (> 80% disability on the Barthel scale), chronic pain or disabling orthopedic conditions, hospitalization in the last three months for a serious medical or surgical condition, anemia (hematocrit < 30%), stroke within the previous year.
• MG patients already performing moderate-intensity physical activity of 150min or more per week, i.e., one of the target interventions.
• Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Observation; 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.
Experimental: Physical activity; 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.	Behavioral: Physical activity; Intervention with physical activity more than 150 minutes of medium to high intensity per week.
Active Comparator: Sleep hygiene intervention; 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.	Behavioral: Sleep hygiene; Intervention with sleep hygiene to optimize sleep duration and quality.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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)	7 months

Other Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Uppsala University
• Investigators: Principal Investigator: Anna Rostedt Punga, MD, PhD, Uppsala University

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: June 7, 2023
• First Submitted That Met QC Criteria: August 14, 2023
• First Posted (Actual): August 15, 2023

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: physical activity; fatigue; lifestyle intervention; OURA
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis
• Other Study ID Numbers: 2023-01455-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Not relevant.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No