Clinical and Neurochemical Effects of Transcranial Magnetic Stimulation (TMS) in Multiple Sclerosis
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 90
- 主要终点
- Comprehensive clinical assessment of the disease
研究概览
简要总结
Background: Transcranial Magnetic Stimulation (TMS) is a technique based on the principles of electromagnetic induction. It applies pulses of magnetic radiation that penetrate the brain tissue, and it is a non-invasive, painless and practically innocuous procedure. Previous studies advocate the therapeutic capacity of TMS in several neurodegenerative and psychiatric processes, both in animal models and in human studies. Its uses in Parkinson's disease, Alzheimer's disease and in Huntington's chorea have shown improvement in the symptomatology and in the molecular profile, and even in the cellular density of the brain. Consequently, the extrapolation of these TMS results in the aforementioned neurodegenerative disease to other entities with etiopathogenic and clinical analogy would raise the relevance and feasibility of its use in multiple sclerosis (MS). The overall objective will be to demonstrate the effectiveness of the TMS in terms of safety and clinical improvement, as well as to observe the molecular changes in relation to the treatment.
Methods and design: Phase I clinical trial, unicentric, controlled, randomised, single blind. A total of 90 patients diagnosed with relapsing-remitting multiple sclerosis (RRMS) who meet all the inclusion criteria and do not present any of the exclusion criteria that are established and from which clinically evaluable results can be obtained. The patients included will be assigned under the 1:1:1 randomization formula, constituting three groups for the present study: 30 patients treated with natalizumab + white (placebo) + 30 patients treated with natalizumab + TMS (1 Hertz) + 30 patients treated with natalizumab + TMS (5 Hertz).
Discussion: Results of this study will inform on the efficiency of the TMS for the treatment of MS. The expected results are that TMS is a useful therapeutic resource to improve clinical status (main parameters) and neurochemical profile (surrogate parameters); both types of parameters will be checked.
详细描述
It is based on the hypothesis that the application of transcranial magnetic stimulation (TMS) at 1 Hertz or 5 Hertz in patients with relapsing-remitting multiple sclerosis (RRMS) implies a neuroprotective effect against the progression of the disease, resulting in a clinical improvement (attenuation of symptoms and signs, as direct measures of the therapeutic effect) and a biochemistry improvement (decrease of serum oxidative stress molecules and acute phase reactants, as indirect measures).
Along with the traditional techniques for measuring biochemical magnitudes, proteomic techniques would allow the identification (and subsequent validation) of molecules that are clearly different in situations of stability-relapse, presence-absence of therapeutic response, better-worse evolution. These molecules (in isolation or considering their characteristics together) could be useful as therapeutic targets or as useful biomarkers for diagnostic or prognostic use.
The main goal is to demonstrate the therapeutic effect of TMS in patients with MS by means of measurement of clinical changes according to the Expanded Disability Status Scale (EDSS). Consequently, the specific objectives are:
- To determine the consequences of the administration of TMS (1 Hertz/5 Hertz) in patients with MS, paying special attention to its clinical impact according to the MSFC scale (Multiple Sclerosis Functional Composite).
- To assess the effect of the application of TMS (1 Hertz/5 Hertz) on fatigue in people with MS, according to the FIS scale (Fatigue Impact Scale).
- To observe the effect of the application of TMS (1 Hertz/5 Hertz) on the degree of depression, according to the Beck scale.
- To study the impact of TMS (Hertz/5 Hz) on cognitive changes in patients with MS, in relation to the BRB scale (Brief Repeatable Battery of Neuropsychological Test).
- To identify the changes induced by the application of TMS (1 Hertz/5 Hertz) on neurochemical biomarkers, oxidative damage, acute phase reactants and in differential expression proteomic profiles, in patients affected by MS.
- To establish the possible associations between the parameters studied and the likely changes that may be observed in them after TMS therapy.
DESIGN:
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, Outcomes Assessor)
盲法说明
Single-blind. Investigator who applies transcranial stimulation knows the kind of treatment (placebo, TMS 1 Hertz, TMS 5 Hertz). The patients don't know the frequency (measured Hertz) which TMS is running (0 Hertz= placebo, 1 Hertz, 5 Hertz) and the device and duration of sessions are the same.
入排标准
- 年龄范围
- 14 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with RRMS in their inflammatory forms who have completed a 14-dose treatment with natalizumab.
- •Normal analytical parameters, defined by: Leukocytes> 3000 / mcl, Neutrophils> 1500 / mcl, Platelets> 100000 / mcl, AST/ALT <2.5 IU / L, Creatinine <2.5 mg / dl.
- •Patients of both sexes aged between 18 and 60 years.
- •EDSS: between 3.0 and 6.5 points.
- •Patients who give their informed consent for participation in the clinical trial.
- •Women of childbearing potential must obtain negative results in a pregnancy test performed at the time of inclusion in the study and commit to using a medically approved method of contraception for the duration of the study.
排除标准
- •Any active or chronic infection, including HIV infection, or hepatitis B or C.
- •History of neoplasia (basal cell carcinoma of the skin and in situ carcinoma in remission are excluded for more than one year).
- •Life expectancy severely limited by other co-morbidities.
- •Endocrine disease such as diabetes, hyper or hypothyroidism.
- •Chronic inflammatory or autoimmune disease such as ulcerative colitis, Crohn's disease, systemic lupus erythematosus and any other form of connective tissue disease or chronic arthropathy.
- •Chronic obstructive pulmonary disease.
- •Severe psychiatric illnesses.
- •Hepatic, or renal, or cardiac dysfunction (including coronary heart disease and heart failure).
- •Chronic anaemia.
- •Pregnancy or risk of pregnancy (including refusal to use contraception).
- •Women in breastfeeding period.
- •Inability to undergo MRI scans.
- •Inability to grant written informed consent.
- •Taking lipid-lowering drugs and vitamin supplements.
- •Treatment with steroids and/or non-steroidal anti-inflammatories, or alcohol intake 40 hours before the blood extraction and/or development of the different tests.
- •Chronic alcoholism and/or abuse of drugs of abuse (sporadic or chronic).
- •Metallic implants in the head.
- •Cardiac pacemaker device.
研究组 & 干预措施
Placebo group
This group will be under standard therapy (natalizumab) plus Transcranial Magnetic Stimulation (TMS) without any frequency (device doesn't running; it means, device turned off) but the same duration of sessions.
干预措施: Placebos (Drug)
Group under TMS 1 Hertz treatment
1 Hertz group (1 Hertz ) will be under standard therapy (natalizumab) plus Transcranial Magnetic Stimulation (TMS) running with a frequency of 1 Hertz.
干预措施: Transcranial Magnetic Stimulation (TMS) (Device)
Group under TMS 5 Hertz treatment
5 Hertz group (5 Hertz ) will be under standard therapy (natalizumab) plus Transcranial Magnetic Stimulation (TMS) running with a frequency of 5 Hertz .
干预措施: Transcranial Magnetic Stimulation (TMS) (Device)
结局指标
主要结局
Comprehensive clinical assessment of the disease
时间窗: up 1 year
Multiple Sclerosis Functional Composite. It consists of three tests: Timed 25-Foot Walk, 9-Hole Peg Test and Paced Auditory Serial Addition Task. Score measured as a function of time. The higher, the worse the patient's condition.
Clinical activity of the disease
时间窗: up 1 year
Expanded Disability Status Scale. Score from 0 (total absence of disability) to 10 (death due to multiple sclerosis).
Cognitive function
时间窗: up 1 year
Brief Repeatable Battery of Neuropsychological Test. It consists of the selective reminding test, the 10/36 spatial recall test, the symbol digit modalities test, the paced auditory serial addition test and the word list generation test. A higher score means a better status in a person.
次要结局
- Image analysis(through study completion, an average of 1 year)
- Carbonylated proteins(through study completion, an average of 1 year)
- glucose(through study completion, an average of 1 year)
- Assessment of fatigue(up 1 year)
- Complete blood count(through study completion, an average of 1 year)
- Routine serum lipids(through study completion, an average of 1 year)
- Depression assessment(up 1 year)
- Lipoperoxidation molecules(through study completion, an average of 1 year)
- Routine serum proteins(through study completion, an average of 1 year)
- Transaminases(through study completion, an average of 1 year)
- creatine kinase (CK)(through study completion, an average of 1 year)
- lactate dehydrogenase(through study completion, an average of 1 year)
研究者
Javier Caballero-Villarraso
Professor
Maimónides Biomedical Research Institute of Córdoba