Neuromodulation of the Left Premotor Cortex With Transcranial Magnetic Stimulation to Alleviate Fatigue in Multiple Sclerosis - a Randomised Controlled Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change from baseline in patient reported fatigue severity, measured by the Fatigue Scale for Motor and Cognitive Symptoms (FSMC) from baseline to +6 days
研究概览
简要总结
The goal of this clinical trial is to learn if repetitive Transcranial Magnetic Stimulation (rTMS) of the left premotor cortex can lessen fatigue in patients with Multiple Sclerosis, and if this is a feasible intervention. It will also give further information on fatigue in Multiple Sclerosis. The main questions it aims to answer is:
- Does premotor rTMS decrease fatigue symptoms in patients with Multiple Sclerosis?
- Is the change in fatigue reflected in an altered balance between brain excitation and inhibition in the targeted premotor cortex?
Researchers will compare real rTMS with sham rTMS (which does not stimulate with a magnetic field), to see if real rTMS works to alleviate fatigue.
Participants will:
- Receive real or sham rTMS for 30 minutes, 5 days in a row
- Visit the clinic before and 6 days after for baseline and follow-up
- Fill out on-line questionnaires 1 day and 4 weeks after the end of intervention
- Undergo a total of 3 brain scans (Magnetic Resonance Imaging at ultra-high field), at baseline, end of intervention, and follow-up
- Undergo lab neurophysiological measurements before and after the first intervention session
- Keep a fatigue diary and wear an activity tracker in the period before and after the intervention
详细描述
BACKGROUND:
Multiple sclerosis (MS) is an immune mediated disease, targeting the central nervous system. Globally, the prevalence and incidence are increasing. It is a chronic condition, with no known definitive cure. Fatigue is among the most disabling MS symptoms, and is highly prevalent afflicting up to 78%-95% of patients. Fatigue in persons with MS (PwMS) is consistently associated with lower quality of life and severity of fatigue is generally associated with employment status, and may worsen over time.
PATHOPHYSIOLOGY:
The pathophysiological basis for fatigue in MS is poorly understood, with several possible contributors. However, trait fatigue in everyday life associates with task-related hyperactivation of the premotor cortex during a non-fatiguing grip force task. Patients who are able to increase premotor activity after performing a fatiguing motor task are less affected by fatigue during everyday life. Taken together, these findings support the hypothesis, that patients suffering from trait fatigue allocate their premotor "neural resources" less efficiently than patients without fatigue. This implies a mismatch in the physiological neuronal inhibition/excitation balance, and is evident as hyperactivity of the premotor cortex during "normal" motor activities, which in turn impedes an efficient upscaling of premotor activity.
CURRENT TREATMENTS:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The TMS stimulation machine (MagPro XP orange edition, MagVenture A/S, Farum, Denmark), in combination with an A/P-coil with a separate active and placebo (sham) side. The sham side is designed to deliver <5% of the magnetic field of the active side, with similar tactile and auditory input.
The coil is designed to be reversible, with no markings as to which side is which. There is an internal sensor that allows the device to determine which side is up. Masking is ensured by a pre-programmed code, unique to each participant, which is input in the device whereafter the device will indicate if the "wrong" side is being used for stimulation.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A confirmed diagnosis of relapse-remitting or secondary progressive multiple sclerosis, according to most recent McDonald's criteria (Thompson et al., 2018). This diagnosis must not be more recent than 3 months
- •Must have fatigue as a complaint, and an FSMC score corresponding to at least moderate fatigue (>53)
- •Stable MS medication for at least 3 months
排除标准
- •Pregnancy, any subject with the potential to become pregnant must ensure against this (e.g. by taking oral contraceptives, or other high efficacy method)
- •MS Relapse or steroid treatment within 3 months prior to inclusion
- •Current treatment targeted towards fatigue, or previous if discontinued within 3 months prior to inclusion
- •History of neurologic disease or other significant medical conditions, aside from MS
- •EDSS > 6.5
- •Major psychiatric disorder, including current clinical depression.
- •Intake of medication that primarily acts on CNS or neurotransmission, except SSRI or SNRI
- •Pacemaker or other implanted electronic devices
- •Any intracranial metal
- •Any metallic implant incompatible with MR scanning
- •Claustrophobia
- •Either patient or their close relatives suffering from epilepsy
- •Current Drug or alcohol abuse
研究组 & 干预措施
Active Repetitive Transcranial Magnetic Stimulation (rTMS)
Active Repetitive Transcranial Magnetic Stimulation (rTMS)
干预措施: Real Repetitive Transcranial Magnetic Stimulation (Device)
Sham Repetitive Transcranial Magnetic Stimulation
Sham Repetitive Transcranial Magnetic Stimulation
干预措施: Sham Repetitive Transcranial Magnetic Stimulation (Device)
结局指标
主要结局
Change from baseline in patient reported fatigue severity, measured by the Fatigue Scale for Motor and Cognitive Symptoms (FSMC) from baseline to +6 days
时间窗: Follow-up at 6 days post intervention. Compared to baseline
Difference in change in score in Fatigue Scale for Motor and Cognitive functions, between baseline and clinical follow-up, between real and sham group. It is a validated 20 item score, designed for fatigue in MS. It has motor and cognitive subscales. Range 20-100. Cut-off for mild, moderate and severe fatigue is 43, 53 and 63 respectively.
次要结局
- Change from baseline in regional brain tissue concentration of glutamate/glutamine in the stimulated premotor cortex, measured by single-voxel Magnetic Resonance Spectroscopy(Day 5 of intervention and 6 days post end of intervention, compared to baseline)
- Change from baseline in Brain tissue concentration of GABA in the stimulated premotor cortex, measured by single-voxel Magnetic Resonance Spectroscopy(Day 5 of intervention and 6 days post end of intervention, compared to baseline)
- Change from baseline in patient-reported fatiguability, measured by the Pittsburgh Fatiguability Score (PFS)(Follow-up at 1, 6 and 28 days post intervention. Compared to baseline.)
- Change from baseline in patient reported fatigue severity, measured by the Fatigue Scale for Motor and Cognitive Symptoms (FSMC)(Follow-up at 1 and 28 days post intervention. Compared to baseline.)
- Change from baseline in objective fatiguability, measured by the Fatiguability Index (FI)(Follow-up at 6 days post intervention. Compared to baseline.)