A phase II trial is currently underway to investigate the potential benefits of repetitive transcranial magnetic stimulation (rTMS) for individuals living with multiple sclerosis (MS). The study focuses on evaluating the safety and preliminary efficacy of rTMS in improving functional outcomes and quality of life for MS patients.
Measuring Functional Outcomes with MSFC
The trial employs the Multiple Sclerosis Functional Composite (MSFC) to determine whether rTMS can lead to tangible improvements in functional abilities. The MSFC comprises three key components: the Symbol Digit Modality Test (SDMT), the 9-Hole Peg Test (9-HPT), and the Timed 25-Foot Walk (T25-FW). These tests assess cognitive function, upper extremity dexterity, and ambulation, respectively.
- Symbol Digit Modality Test (SDMT): This test measures cognitive processing speed by requiring participants to match symbols with numbers within a 90-second timeframe. The SDMT has demonstrated sensitivity in detecting changes in cognitive function and has good test-retest reliability (ICC of 0.85).
- Timed 25-Foot Walk (T25-FW): Participants are instructed to walk 25 feet as quickly and safely as possible. The average of two trials is used for analysis. The T25-FW exhibits high inter-rater and test-retest reliability (ICC=0.86, p≤0.001).
- Nine-Hole Peg Test (9-HPT): This test evaluates upper extremity function by measuring the time it takes for participants to place and remove nine pegs from a board. The 9-HPT has high inter-rater and intra-rater reliability (ICC=0.98) and is capable of detecting minor impairments in hand function. To account for practice effects, participants complete three practice sessions before baseline testing.
Assessing Patient-Reported Outcomes (PROMs)
In addition to the MSFC, the trial incorporates patient-reported outcome measures (PROMs) to capture the subjective experiences of participants. These questionnaires assess various aspects of well-being, including anxiety, depression, fatigue, quality of life, and sleep quality. The questionnaires include:
- Hospital Anxiety and Depression Scale (HADS): A 14-item self-assessment scale that measures anxiety and depression.
- Assessment of Quality of Life-8D (AQoL-8D): Assesses physical and psychosocial aspects of quality of life across eight dimensions.
- Fatigue Severity Scale (FSS): A nine-item questionnaire that measures physical and cognitive aspects of fatigue and fatigue severity.
- Pittsburgh Sleep Quality Index (PSQI): An instrument used to measure sleep quality over the past month.
Monitoring Safety and Tolerability
The trial meticulously monitors adverse events (AEs) to ensure the safety and tolerability of rTMS for individuals with MS. AEs are recorded at each intervention visit and coded using the Medical Dictionary for Regulatory Activities (MedDRA). The severity, relationship to the study intervention, and outcome of each AE are carefully assessed by blinded investigators.
Advanced MRI Analysis
Participants undergo MRI brain scans before and after the intervention period. These scans are used to assess changes in brain tissue volumes, lesion number, and lesion volume. Advanced MRI metrics, such as diffusion tensor imaging (DTI) and magnetization transfer ratio (MTR), are also employed to evaluate microstructural changes in the brain.
Data Management and Confidentiality
Data is collected and managed in accordance with Good Clinical Practice guidelines, The Privacy Act (1988), and the Australian Code for the Responsible Conduct of Research, 2018. REDCap, a secure web application, is used to manage research data. Participants' identifiable information is kept confidential, and all data is pseudonymized to protect their privacy.
This trial represents a significant effort to explore the potential of rTMS as a therapeutic intervention for multiple sclerosis. By combining objective measures of functional performance with patient-reported outcomes and advanced neuroimaging techniques, the study aims to provide a comprehensive assessment of the benefits and risks associated with rTMS treatment for MS patients.
