A Feasibility Trial of Neuromodulation With Connectivity-Guided Intermittent Theta Burst Stimulation for Cognitive Impairment in Multiple Sclerosis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Feasibility of Trial Procedures
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Feasibility of Trial Procedures
时间窗: 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
次要结局
- The Brief Visuospatial Memory Test Revised (BVMT-R) Total learning(8 weeks)
- General Anxiety Disorder Scale(8 weeks)
- Perceived Deficits Questionnaire (PDQ)(8 weeks)
- Interviews - perceived differences(1 week)
- The Brief Visuospatial Memory Test Revised (BVMT-R) Delayed recall(8 weeks)
- The Brief Visuospatial Memory Test Revised (BVMT-R) Percent retained(8 weeks)
- Patient Health Questionnaire - Depression(8 weeks)
- The Modified Fatigue Impact Scale (MFIS)(8 weeks)
- Change in effective connectivity between left dorsolateral prefrontal cortex and left caudate nucleus(5 weeks)
- Safety outcomes of iTBS(4 weeks)
- Undesired effects of iTBS(4 weeks)
- The Brief Visuospatial Memory Test Revised (BVMT-R) Recognition response bias(8 weeks)
- The California Verbal Learning Test-II (CVLT-II)(8 weeks)
- The Symbol Digit Modalities Test (SDMT)(8 weeks)
- Digit Span Forwards (from WAIS-IV)(8 weeks)
- The Edinburgh Handedness Inventory (EHI)(1 week)
- iTBS Experience Questionnaire - Tolerability(1 week)
- Interviews - Tolerability(1 week)
- Feasibility of recruitment(1 week)
- The Brief Visuospatial Memory Test Revised (BVMT-R) Trials 1-3.(8 weeks)
- iTBS Experience Questionnaire - Blinding(1 week)
- Interviews - Acceptability(1 week)
- Interviews - Improvements(1 week)
- The Brief Visuospatial Memory Test Revised (BVMT-R) Learning(8 weeks)
- The Brief Visuospatial Memory Test Revised (BVMT-R) Recognition hits(8 weeks)
- The Brief Visuospatial Memory Test Revised (BVMT-R) Recognition false alarms(8 weeks)
- The Brief Visuospatial Memory Test Revised (BVMT-R) Recognition discrimination index(8 weeks)
- Digit Span Backwards (from WAIS-IV)(8 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)(5 weeks)
- iTBS Experience Questionnaire - Acceptability(1 week)
- Post-participation workshop(1 week)