Feasibility of Neuromodulation With Connectivity-Guided iTBS for Cognitive Impairment in MS
TMS4MS
A Feasibility Trial of Neuromodulation With Connectivity-Guided Intermittent Theta Burst Stimulation for Cognitive Impairment in Multiple Sclerosis
1 other identifier
interventional
40
1 country
1
Brief Summary
Cognitive difficulties can affect many people who live with multiple sclerosis (MS). These difficulties, such as within thinking, memory, and problem solving, can have an impact on important aspects of an individual's life, including their daily activities, work, and how they manage their condition. Previous studies have suggested that cognitive difficulties affect approximately 40-70% of people living with MS, yet there are currently no treatments to target these problems. Recent research has directed towards a non-invasive intervention which stimulates a part of the brain (called the dorsolateral prefrontal cortex, or DLPFC for short) which is reported to participate in cognitive processes, such as memory, thinking, and attention. This intervention, called "intermittent theta burst stimulation" (iTBS), involves placing a magnetic device to the skull to activate the DLPFC underneath. This technique has been used successfully in the treatment of depression and is widely considered safe and painless. Previous studies have also shown that iTBS intervention can lead to improvements in cognitive processes. Before the investigators can progress to a large trial to explore its clinical effectiveness for reducing cognitive problems for people with MS, some aspects regarding its feasibility need to be clarified, for example whether it is an acceptable and tolerable intervention for people living with MS. A single-centre, mixed methods feasibility randomised controlled trial will be conducted to compare four groups (10 participants each) of iTBS administration. At baseline, End of Intervention (EOI), and 8-week follow up, the investigators will complete outcome measures to evaluate cognition, mood and fatigue. Participants will also undergo MRI scans at baseline and EOI. Following participation, participants will be interviews and the investigators will organise a post-participation workshop to explore their experiences of the trial, including the tolerability of the protocol and acceptability of the visit schedule, and any differences in cognition.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable multiple-sclerosis
Started Jun 2022
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 8, 2021
CompletedFirst Posted
Study publicly available on registry
June 18, 2021
CompletedStudy Start
First participant enrolled
June 1, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2023
CompletedJune 12, 2023
June 1, 2023
1.2 years
June 8, 2021
June 9, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Feasibility of Trial Procedures
Number of sessions attended according to the protocol Number of missed/rescheduled appointments Reasons for non-attendance Completion of end of intervention assessments Completion of 8 weeks follow up assessments
8 weeks
Secondary Outcomes (31)
Feasibility of recruitment
1 week
The Brief Visuospatial Memory Test Revised (BVMT-R) Trials 1-3.
8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Total learning
8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Learning
8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Delayed recall
8 weeks
- +26 more secondary outcomes
Study Arms (4)
Group 1
ACTIVE COMPARATORiTBS intervention lasting 30 minutes, given 4 days a week, for 1 week
Group 2
ACTIVE COMPARATORiTBS intervention lasting 30 minutes, given 4 days a week, for 2 weeks
Group 3
ACTIVE COMPARATORiTBS intervention lasting 30 minutes, given 4 days a week, for 4 weeks
Group 4
SHAM COMPARATORSham iTBS intervention lasting 30 minutes, given 4 days a week, for 2 weeks.
Interventions
The localisation of the left dorsolateral prefrontal cortex (DLPFC) target will be identified using effective connectivity of the left caudate to identify the maximally-connected locus in the left DLFPC. Following this the iTBS will be administered to the target coordinates identified using the neuronavigation software available with the system. Connectivity-guided iTBS is then administered using a 70mm Double Air Film Coil (Magstim, Whitland, Dyfed, UK), connected to a Magstim Super Rapid-2 Plus-1 stimulator. The administration comprises bursts of 3 pulses at 50Hz with a power of 80% motor threshold at a burst frequency of 5 Hz (i.e., every 200ms) for 2 seconds, repeated every 10 seconds for a total of 190 seconds (600 pulses). Blocks are repeated a total of 3 times, with 5-minute rest intervals between blocks. During left DLPFC stimulation, the TBS coil is held by a support tangentially to the skull, with the axis of the coil angled approximately 90 degrees from the midsagittal axis.
The sham iTBS administration is performed under the same conditions and with an identical protocol and equipment to the full administration, except that it uses a commercially available sham iTBS coil designed for use in double-blind trials. This sham coil looks like the real coil and connects to the iTBS unit but delivers only a very weak and shallow stimulation thus simulating the sounds made by the real iTBS coil.
Eligibility Criteria
You may qualify if:
- Aged between 18 - 69 years.
- Received a diagnosis of MS (any type of MS) at least 12 months prior to baseline assessment.
- Report cognitive problems, as determined by a cut-off score of 55 or lower on the oral SDMT
- Ability to give informed consent
- Able to commit to regular attendance in clinic, for up to 4 times a week for 4 weeks and follow up appointment eight weeks after the end of trial procedures.
You may not qualify if:
- Diagnosed with depression or scores ≥15 on the Patient Health Questionnaire-9
- Medical history of, or self-reported, seizures
- Neurological conditions (in addition to MS), e.g., brain neoplasm, cerebrovascular events, epilepsy, prior brain injury or brain surgery
- Contraindications to MRI scanning (identified by standard MRI safety screening questionnaire).
- Contraindications to TMS, including hairstyles or piercings that would impair magnetic transmission which cannot be altered to ensure effective intervention
- Frequent panic attacks which are likely to prevent regular attendance or participation in MRI/TMS procedures
- Prior TMS intervention
- Pregnancy
- MS relapse within the preceding 6 weeks
- Significant mobility problems if they are likely to preclude regular attendance in clinic, for up to 4 times a week for 4 weeks
- Involved with any other clinical trials involving medical procedures, interventions or treatment.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Queen's Medical Centre
Nottingham, Nottinghamshire, United Kingdom
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, OUTCOMES ASSESSOR
- Masking Details
- Participants will not be told whether they have been allocated to an active iTBS or sham iTBS administration until the end of their study participation, where they will be informed whether they received active or sham iTBS administration. The two technicians (including the research fellow) administering the iTBS will not be blind to group allocation. The RA conducting the cognitive assessments and analysing these (and the questionnaires) will be blinded to group allocation. We aim to stagger the commencement of the iTBS intervention schedule per group (with those in Group C \[4-week intervention schedule\] to begin first), to avoid participants returning for their EOI assessments 1, 2, or 4 weeks later depending upon group allocation. We hope that this will minimise the chance of unblinding the RA to group allocation.
- Purpose
- OTHER
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 8, 2021
First Posted
June 18, 2021
Study Start
June 1, 2022
Primary Completion
August 1, 2023
Study Completion
December 1, 2023
Last Updated
June 12, 2023
Record last verified: 2023-06