Multiple SclerosisTMS4MSNCT04931953
Feasibility of Neuromodulation With Connectivity-Guided iTBS for Cognitive Impairment in MS
A study testing Intermittent theta burst stimulation (iTBS) in people with Multiple Sclerosis and Cognitive Impairment, run by University of Nottingham at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Multiple Sclerosis, Cognitive Impairment
- What is being tested?
- Intermittent theta burst stimulation (iTBS)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Jun 2022to Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Queen's Medical Centre
Nottingham, Nottinghamshire
Robert Dineen
About this study
Official title: A Feasibility Trial of Neuromodulation With Connectivity-Guided Intermittent Theta Burst Stimulation for Cognitive Impairment in Multiple Sclerosis
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.
Read the detailed description
The primary objective is to assess the feasibility of the trial procedures, in terms of their acceptability and tolerability for pwMS who have cognitive impairment. For this aim, the completion of the intervention schedule will be measured (e.g., attending all sessions per the protocol, considering any missed appointments and reasons for non-attendance where possible) including the end of intervention assessments, as well as the 8-week follow up to ascertain participant willingness to complete the full study.
Participants will be randomly allocated to one of four groups (Group 1: 4 administrations of intermittent theta burst stimulation (iTBS) over 1 week; Group 2: 8 administrations of iTBS over 2 weeks; Group 3: 16 administrations of iTBS over 4 weeks; Group 4: 8 administrations of sham iTBS over 2 weeks). Participants will not be aware whether they have been allocated to receive active or sham iTBS administration.
Intervention - Active iTBS: Active connectivity-guided iTBS will be administered to the left dorsolateral prefrontal cortex (DLPFC). 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 minutes rest intervals between blocks. (Duration and frequency: 30 min, 4 times a week for up to 4 weeks depending on group).
Sham iTBS: 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.
At baseline, End of Intervention (EOI), and 8-week follow up, outcome measures will be completed to evaluate cognition, mood and fatigue. Participants will also undergo MRI scans at baseline and EOI. The purpose of the MRI is to allow identification of the exact location over which the iTBS intervention will be applied, and it will allow measurement of brain function before iTBS intervention (or sham).
The MRI scan will include:
- High resolution T1-weighted structural brain image for image co-registration,
- Resting-state functional MRI (rs-fMRI) for connectivity-guided neuronavigation,
- Fluid attenuated inversion recovery (FLAIR)
- Diffusion tensor imaging (DTI) acquisitions to quantification spatial mapping of macro- and mircrostructural white matter injury,
- Arterial Spin Labelling (ASL) perfusion imaging to map cerebral blood flow.
- Task related functional MRI - N-Back task.
The investigators have developed a questionnaire to explore tolerability and acceptability of the procedures, and participants will also be invited to discuss their experience of participating in the trial at interview 8 weeks post-intervention.
Finally, at the end of the study, the investigators aim to host a post-participation workshop at the beginning of month 28, following collection and analysis of main outcomes. Depending on covid-safe recommendations from the government and university, this may be via video call or at a venue. All participants will be invited to discuss whether the experience of participation (varying from 1-week to 4-weeks) can inform which of intervention regime investigators should take forward into a subsequent pilot trial, to expand on the preliminary data analysis from the qualitative interviews. Investigators will explore the magnitude and nature of the effect on cognition that would be needed to be achieved to give a meaningful change to them personally, such that the iTBS interventions of different durations would be warranted. For example, participants may feel that only a major improvement in day-to-day cognition would justify a 4-week intervention, whereas others may feel that any benefit would justify this. These issues will be explored to inform future trial design.
- Conditions
- Multiple Sclerosis, Cognitive Impairment
- Being tested
- Intermittent theta burst stimulation (iTBS), Sham Intermittent theta burst stimulation (iTBS)
- Medical subject headings
- Multiple Sclerosis, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intermittent theta burst stimulation (iTBS)Other
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.
Sham Intermittent theta burst stimulation (iTBS)Other
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.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Active comparator | iTBS intervention lasting 30 minutes, given 4 days a week, for 1 week Receives: Other: Intermittent theta burst stimulation (iTBS) |
| Group 2 | Active comparator | iTBS intervention lasting 30 minutes, given 4 days a week, for 2 weeks Receives: Other: Intermittent theta burst stimulation (iTBS) |
| Group 3 | Active comparator | iTBS intervention lasting 30 minutes, given 4 days a week, for 4 weeks Receives: Other: Intermittent theta burst stimulation (iTBS) |
| Group 4 | Sham comparator | Sham iTBS intervention lasting 30 minutes, given 4 days a week, for 2 weeks. Receives: Other: Sham Intermittent theta burst stimulation (iTBS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 8 weeks
Secondary outcomes (31)
Feasibility of recruitment
Proportion of eligible and consenting participants
Measured: 1 week
The Brief Visuospatial Memory Test Revised (BVMT-R) Trials 1-3.
Raw scores range from 0 to 12 for each trial and reflect accuracy and correct placement (higher scores indicate better outcome)
Measured: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Total learning
Sum of scores across the three trials (min: 0, max: 36; higher scores indicate better outcome).
Measured: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Learning
The best of Trial 2 or 3 minus the Trial 1 score (min 0 max 23, higher scores indicate better outcome)
Measured: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Delayed recall
Raw scores range from 0 to 12 (max) and reflect recall of designs after 25-min delay. Higher scores indicate better outcome.
Measured: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Percent retained
Scores range from 1 to 100 (max) and reflect the amount originally learned that was retained across the delay. Higher scores indicate better outcome.
Measured: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Recognition hits
- Number of target figures correctly recognized; scores range from 0 to 6 (max). Higher scores indicate better outcome.
Measured: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Recognition false alarms
Number of distractors incorrectly recognized as targets; scores range from 0 to 6 (max). Higher scores indicate better outcome.
Measured: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Recognition discrimination index
Recognition hits minus recognition false alarms; scores range from -6 to 6 (max). Higher scores indicate better outcome.
Measured: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Recognition response bias
Scores range from 0.00 to 1.00 (max) and reflect the tendency (or lack of) to answer "yes" to a recognition item. Higher scores indicate better outcome.
Measured: 8 weeks
The California Verbal Learning Test-II (CVLT-II)
A computer administration and scoring system generates score, graphs a learning curve, and provides learning parameters, response errors and interference effects. Higher scores indicate better outcome.
Measured: 8 weeks
The Symbol Digit Modalities Test (SDMT)
Raw score of correct items named per 90 seconds. Minimum value: 0 Maximum value: 130. Higher scores indicate better outcome.
Measured: 8 weeks
Digit Span Forwards (from WAIS-IV)
Raw score, minimum 0, maximum 16. Higher scores indicate better outcome.
Measured: 8 weeks
Digit Span Backwards (from WAIS-IV)
Raw score, minimum 0, maximum 16. Higher scores indicate better outcome.
Measured: 8 weeks
Patient Health Questionnaire - Depression
Self-rated mood. Raw score, minimum 0, maximum 27. Lower scores indicate better outcome.
Measured: 8 weeks
General Anxiety Disorder Scale
Self-rated anxiety. Raw score, minimum 0, maximum 21. Lower scores indicate better outcome.
Measured: 8 weeks
Perceived Deficits Questionnaire (PDQ)
Self-reported cognitive impairment. Raw score, minimum 0, maximum 80. Lower scores indicate better outcome.
Measured: 8 weeks
The Modified Fatigue Impact Scale (MFIS)
Self-reported fatigue. Raw score, minimum 0, maximum 84. Lower scores indicate better outcome.
Measured: 8 weeks
The Edinburgh Handedness Inventory (EHI)
Self-rated handedness to determine whether one favours left or right-handedness. It is not scored; result will be binary (left/right).
Measured: 1 week
Change in effective connectivity between left dorsolateral prefrontal cortex and left caudate nucleus
As above
Measured: 5 weeks
Change in cerebral blood flow in the left dorsolateral prefrontal cortex and in the left caudate nucleus (normalised to whole brain cerebral blood flow)
As above
Measured: 5 weeks
Safety outcomes of iTBS
Number of participants with treatment-related adverse events and number of events each, as reported to research team
Measured: 4 weeks
Undesired effects of iTBS
Number of participants with self reported negative effects e.g., headaches, dizziness
Measured: 4 weeks
iTBS Experience Questionnaire - Tolerability
Unpleasant sensations of iTBS. Minimum score 0, maximum score 15. Higher indicates worse outcome.
Measured: 1 week
iTBS Experience Questionnaire - Acceptability
Minimum score 0, maximum score 30. Higher score indicates better outcome.
Measured: 1 week
iTBS Experience Questionnaire - Blinding
Number of participants who correctly guessed allocation to sham/active iTBS intervention
Measured: 1 week
Interviews - Tolerability
Tolerability of the trial procedures - qualitative analysis via framework method
Measured: 1 week
Interviews - Acceptability
Acceptability of the trial procedures of the trial procedures- qualitative analysis via framework method
Measured: 1 week
Interviews - perceived differences
Subjective perceived differences in cognitive abilities in daily life - qualitative analysis via framework method
Measured: 1 week
Interviews - Improvements
Suggested improvements to refine trial procedures - qualitative analysis via framework method
Measured: 1 week
Post-participation workshop
A semi-structured focus group schedule will explore qualitative data regarding meaningful changes to cognition/mood and how much change would be expected given the requirements of the intervention at the post-participation workshop. This will be analysed using framework analysis.
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2021
- Study start1 Jun 2022
- Primary completionAug 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04931953
- Sponsor's protocol ID
- 21038
- Acronym
- TMS4MS
- Status last verified
- Jun 2023
- First submitted
- 8 Jun 2021
- Last updated
- 12 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Feasibility Trial of Neuromodulation With Connectivity-Guided Intermittent Theta Burst Stimulation for Cognitive Impairment in Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT04931953
- Acronym / sponsor ID
- TMS4MS / 21038
- Conditions
- Multiple Sclerosis, Cognitive Impairment
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- 1 Jun 2022 (actual)
- Primary completion
- Aug 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 18 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The primary objective is to assess the feasibility of the trial procedures, in terms of their acceptability and tolerability for pwMS who have cognitive impairment. For this aim, the completion of the intervention schedule will be measured (e.g., attending all sessions per the protocol, considering any missed appointments and reasons for non-attendance where possible) including the end of intervention assessments, as well as the 8-week follow up to ascertain participant willingness to complete the full study.
Participants will be randomly allocated to one of four groups (Group 1: 4 administrations of intermittent theta burst stimulation (iTBS) over 1 week; Group 2: 8 administrations of iTBS over 2 weeks; Group 3: 16 administrations of iTBS over 4 weeks; Group 4: 8 administrations of sham iTBS over 2 weeks). Participants will not be aware whether they have been allocated to receive active or sham iTBS administration.
Intervention - Active iTBS: Active connectivity-guided iTBS will be administered to the left dorsolateral prefrontal cortex (DLPFC). 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 minutes rest intervals between blocks. (Duration and frequency: 30 min, 4 times a week for up to 4 weeks depending on group).
Sham iTBS: 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.
At baseline, End of Intervention (EOI), and 8-week follow up, outcome measures will be completed to evaluate cognition, mood and fatigue. Participants will also undergo MRI scans at baseline and EOI. The purpose of the MRI is to allow identification of the exact location over which the iTBS intervention will be applied, and it will allow measurement of brain function before iTBS intervention (or sham).
The MRI scan will include:
- High resolution T1-weighted structural brain image for image co-registration,
- Resting-state functional MRI (rs-fMRI) for connectivity-guided neuronavigation,
- Fluid attenuated inversion recovery (FLAIR)
- Diffusion tensor imaging (DTI) acquisitions to quantification spatial mapping of macro- and mircrostructural white matter injury,
- Arterial Spin Labelling (ASL) perfusion imaging to map cerebral blood flow.
- Task related functional MRI - N-Back task.
The investigators have developed a questionnaire to explore tolerability and acceptability of the procedures, and participants will also be invited to discuss their experience of participating in the trial at interview 8 weeks post-intervention.
Finally, at the end of the study, the investigators aim to host a post-participation workshop at the beginning of month 28, following collection and analysis of main outcomes. Depending on covid-safe recommendations from the government and university, this may be via video call or at a venue. All participants will be invited to discuss whether the experience of participation (varying from 1-week to 4-weeks) can inform which of intervention regime investigators should take forward into a subsequent pilot trial, to expand on the preliminary data analysis from the qualitative interviews. Investigators will explore the magnitude and nature of the effect on cognition that would be needed to be achieved to give a meaningful change to them personally, such that the iTBS interventions of different durations would be warranted. For example, participants may feel that only a major improvement in day-to-day cognition would justify a 4-week intervention, whereas others may feel that any benefit would justify this. These issues will be explored to inform future trial design.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Active comparator | Other: Intermittent theta burst stimulation (iTBS)iTBS intervention lasting 30 minutes, given 4 days a week, for 1 week |
| Group 2 | Active comparator | Other: Intermittent theta burst stimulation (iTBS)iTBS intervention lasting 30 minutes, given 4 days a week, for 2 weeks |
| Group 3 | Active comparator | Other: Intermittent theta burst stimulation (iTBS)iTBS intervention lasting 30 minutes, given 4 days a week, for 4 weeks |
| Group 4 | Sham comparator | Other: Sham Intermittent theta burst stimulation (iTBS)Sham iTBS intervention lasting 30 minutes, given 4 days a week, for 2 weeks. |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intermittent theta burst stimulation (iTBS)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. | Other | Group 1, Group 2, Group 3 |
| Sham Intermittent theta burst stimulation (iTBS)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. | Other | Group 4 |
Primary outcome
Feasibility of Trial Procedures
Time frame: 8 weeks
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
31 secondary outcomes
Feasibility of recruitment
Time frame: 1 week
The Brief Visuospatial Memory Test Revised (BVMT-R) Trials 1-3.
Time frame: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Total learning
Time frame: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Learning
Time frame: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Delayed recall
Time frame: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Percent retained
Time frame: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Recognition hits
Time frame: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Recognition false alarms
Time frame: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Recognition discrimination index
Time frame: 8 weeks
The Brief Visuospatial Memory Test Revised (BVMT-R) Recognition response bias
Time frame: 8 weeks
The California Verbal Learning Test-II (CVLT-II)
Time frame: 8 weeks
The Symbol Digit Modalities Test (SDMT)
Time frame: 8 weeks
Digit Span Forwards (from WAIS-IV)
Time frame: 8 weeks
Digit Span Backwards (from WAIS-IV)
Time frame: 8 weeks
Patient Health Questionnaire - Depression
Time frame: 8 weeks
General Anxiety Disorder Scale
Time frame: 8 weeks
Perceived Deficits Questionnaire (PDQ)
Time frame: 8 weeks
The Modified Fatigue Impact Scale (MFIS)
Time frame: 8 weeks
The Edinburgh Handedness Inventory (EHI)
Time frame: 1 week
Change in effective connectivity between left dorsolateral prefrontal cortex and left caudate nucleus
Time frame: 5 weeks
Change in cerebral blood flow in the left dorsolateral prefrontal cortex and in the left caudate nucleus (normalised to whole brain cerebral blood flow)
Time frame: 5 weeks
Safety outcomes of iTBS
Time frame: 4 weeks
Undesired effects of iTBS
Time frame: 4 weeks
iTBS Experience Questionnaire - Tolerability
Time frame: 1 week
iTBS Experience Questionnaire - Acceptability
Time frame: 1 week
iTBS Experience Questionnaire - Blinding
Time frame: 1 week
Interviews - Tolerability
Time frame: 1 week
Interviews - Acceptability
Time frame: 1 week
Interviews - perceived differences
Time frame: 1 week
Interviews - Improvements
Time frame: 1 week
Post-participation workshop
Time frame: 1 week
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intermittent theta burst stimulation (iTBS) in people with Multiple Sclerosis and Cognitive Impairment, run by University of Nottingham at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Robert A Dineen (01158231173, Rob.Dineen@nottingham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of Trial Procedures (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2023.