Neuromuscular Magnetic Stimulation Counteracts Muscle Decline in ALS Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 22
- 主要终点
- Change from baseline to Week 2 in the muscle strength measured by Medical Research Council Muscle Scale (MRC).
研究概览
简要总结
Aim of the study is to verify whether neuromuscular magnetic stimulation can improve muscle function in spinal-onset Amyotrophic Lateral Sclerosis (ALS) patients.
详细描述
Background: Amyotrophic lateral sclerosis (ALS) is a multi-factorial and multi-systemic pathology associated with motor neuron degeneration, muscle atrophy and paralysis. Mounting evidence suggests that the earliest presymptomatic functional and pathological changes are occurring distally in axons and at the neuromuscular junction (NMJ). These changes precede, and can be independent of the loss of cell bodies or alterations in other cell types already linked to the ALS disease process. In line with these studies, we found that in human ALS muscles the acetylcholine receptors (AChRs) are less sensitive to ACh than denervated non-ALS muscles. It has been also reported that muscle specific expression of mutant superoxide dismutase (SOD1) gene induces muscle atrophy, significant reduction in muscle strength, mitochondrial dysfunction, microgliosis, and neuronal degeneration, suggesting that retrograde signals from muscle to nerve may contribute to synapse and axon damage. This suggests that skeletal muscle is an important target for therapeutic intervention. Neuromuscular system may be artificially stimulated either by an electrical stimulation (ES) or by time-varying electromagnetic fields. Neuromuscular magnetic stimulation (NMMS) has been proposed as an alternative, non-invasive, stimulation technique.
Objective
aim of the study is to verify whether neuromuscular magnetic stimulation can improve muscle function in spinal-onset Amyotrophic Lateral Sclerosis (ALS) patients. We will study if neuromuscular magnetic stimulation can counteract muscle atrophy by promoting the modulation of factors associated with muscle catabolism and/or increasing the efficacy of nicotinic acetylcholine receptors.
Methods: At the baseline visit, ALS patients will be randomized in two groups to receive daily real neuromuscular magnetic stimulation in one arm and sham neuromuscular magnetic stimulation in the opposite arm for two weeks. All patients will undergo median nerve conduction study and a clinical examination, including handgrip strength test and evaluation of upper limbs muscle strength by Medical Research Council Muscle Scale. At the end of the stimulation procedures, a needle muscle biopsy will be performed bilaterally from flexor carpi radialis muscle. Muscle samples will be used to perform histomorphometric and molecular analysis and electrophysiological recordings of acetylcholine evoked currents.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
All the electrophysiological experiments will be performed in double-blind fashion.
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •diagnosis of probable or definite ALS with spinal-onset
- •right-handed patients
- •a bilateral symmetric muscular deficit in flexor carpi radialis muscle or flexor digitorum profundus muscle (defined by a MRC Muscle Scale score of 3-4/5)
排除标准
- •history of epilepsy or severe headaches,
- •pregnancy or breast-feeding
- •patients with implanted cardiac pacemaker, neurostimulators, surgical clips or medical pumps
- •presenting any other comorbid condition affecting the possibility of completing the study
研究组 & 干预措施
Right-real NMMS Group
It will receive a real stimulation (rNMMS) of the right arm and a sham stimulation (sNMMS) of the left arm
干预措施: Neuromuscular magnetic stimulation (NMMS) (Device)
Left-real NMMS Group
It will receive a rNMMS of the left arm and a sNMMS of the right arm
干预措施: Neuromuscular magnetic stimulation (NMMS) (Device)
结局指标
主要结局
Change from baseline to Week 2 in the muscle strength measured by Medical Research Council Muscle Scale (MRC).
时间窗: Baseline to Week 2
Evaluation of the efficacy of NMMS in improving the muscular strength in ALS patients as measured by MRC-score (numeric scale, normal value: 35 for upper limbs, 40 for lower limbs).
次要结局
- Change from baseline to Week 2 in the amplitude of the ACh-evoked currents (IACh) for nicotinic acetylcholine receptors(Baseline to Week 2)
- Change from baseline to Week 2 in the Compound Muscle Action Potential (CMAP) amplitude from flexor carpi radialis(Baseline to Week 2)
- Change from baseline to Week 2 on levels of Muscle Atrophy F-box (MAFbx)/Atrogin-1 and Muscle Ring-Finger Protein 1 (MuRF-1)(Baseline to Week 2)
- Change from baseline to Week 2 in the muscle strength measured by handgrip dynamometry(Baseline to Week 2)
- Change from baseline to Week 2 on levels of insulin-like growth factor-1 (IGF-1) and Myostatin(Baseline to Week 2)
- Change from baseline to Week 2 on the diameter size of muscle fibers(Baseline to Week 2)
研究者
Maurizio Inghilleri
Associate Professor
University of Roma La Sapienza