Please select the eligibility criteria that correspond to the clinical trial below.
Title: Repetitive Transcranial Magnetic Stimulation in Amyotrophic Lateral Sclerosis
Brief Summary: The investigators' preliminary studies demonstrated that repetitive transcranial magnetic stimulation (rTMS) of the brain may determine a slight slowing in the rate of disease progression in ALS patients (Di Lazzaro et al 2004, 2006). The aim of this study is to investigate whether rTMS of the motor cortex performed over a long period of time (12 months) in a group of patients with ALS, can have a more pronounced beneficial effect. The investigators will compare the disease progression in two groups of patients: the first group of patients will be treated with real rTMS (one week daily treatment every month) and the second group of patients will be treated with sham (placebo) rTMS.


Options:
A: Inclusion Criteria:

* patients aged 25 and 80 years
* female patients who are either postmenopausal for at least 24 month or who are willing and able to practice the methods of contraception following the Pharmion-Risk Managment Program (PRMP)
* Male patients who are willing and able to practice the methods of contraception along with their female partners of childbearing potential following the PRMP
* Clinical diagnosis of probable and definite ALS
* Sporadic or familial ALS
* Onset of pareses for no more than 4 years
* Vital capacity equal to or more than 65% of the predicted value
* Treatment with riluzole 100mg/day
* Patients who are willing to give informed consent

Exclusion Criteria:

* pregnancy or breast feeding
* female patients who are unwilling or unable to practice the methods of contraception following the Pharmion-Risk Managment Program (PRMP)
* Male patients who are willing and able to practice the methods of contraception along with their female partners of childbearing potential following the PRMP
* Patients unlikely to comply with the PRMP and other study requirements
* Patients with significant sensory abnormalities, dementia, uncompensated medical illnesses and psychiatric disorders
* Laboratory abnormalities consistent with clinically significant cardiovascular, respiratory, haematological, metabolic, hepatic and renal disease
* Infectious disease including HIV, hepatitis B and C
* monoclonal gammopathy of unknown significance (MGUS)
* History of substance abuse within the past year
* History of recurrent thrombosis
* Continuous non-invasive ventilation (ventilation-free interval equal to or less than 2 hours daily)
* Tracheotomy and invasive ventilation
* Treatment with investigational drug within 3 months prior to screening
* patients with clinically signifikant sensory polyneuropathy (inflammatory neuropathy cause and treatment sensory sum score - ISS ≥ 2)
* patients with sleep disorder (Epworth Sleeping Scale-ESS ≥ 10)
B: Inclusion Criteria:

* Eligible patients should have a diagnosis of definite ALS according to the El Escorial revised criteria with clear clinical upper and lower motor neuron signs.

Exclusion Criteria:

* Contraindications to transcranial magnetic stimulation:

  * Tracheostomy
  * Pace-maker
  * Implanted metallic devices
  * Epilepsy
C: Inclusion Criteria:

* Definite, probable, or probable-laboratory supported ALS according to the revised El Escorial World Federation of Neurology criteria.
* Intake of riluzole 50 mg twice a day (bid)
* A disease duration at inclusion of more than 6 months and less than 36 months \[inclusive\] (disease onset is defined as the date of first symptoms excluding muscle cramps and fasciculations)
* Vital capacity (VC%) ≥ 70% of normal value (slow expiration, best of a minimum of three and a maximum of five measurements, with a respiratory function validly assessable and a spontaneous, non-assisted ventilation)
* Ages 18 - 85 years (inclusive)
* Capable of thoroughly understanding the trial information given; has signed the informed consent.

Exclusion Criteria:

* Tracheostomy, tracheostomal ventilation of any type, non-invasive ventilation more than 16 hours/ day, or supplemental oxygen during the last three months prior to inclusion.
* Any medical condition or intoxication known to have an association with motor neuron dysfunction, which might confound or obscure the diagnosis of ALS.
* Presence of any concomitant life-threatening disease or any disease or impairment likely to interfere with functional assessment.
* Confirmed hepatic insufficiency or abnormal liver function (ASAT, ALAT greater than twice the upper limit of normal range).
D: Inclusion Criteria:

* Familial or sporadic ALS
* Participants diagnosed with laboratory supported probable, clinically possible, probable or definite ALS according to the World Federation of Neurology Revised El Escorial criteria
* Disease duration from symptom onset no greater than 36 months at the Screening Visit
* Age 18 years or older
* Capable of providing informed consent and complying with trial procedures
* On a stable dose of riluzole 50 milligrams (mg) twice per day(bid) for at least 30 days prior to screening
* Vital capacity (VC) equal to or more than 60% predicted normal value for gender, height and age at the Screening Visit
* Creatinine \<1.5 milligrams per deciliter (mg/dl) \[133 micromoles per liter (umol/L\]
* Participants maintained on thyroid medication must be euthyroid for at least 3 months before the Screening Visit.
* Participants with psoriasis must have inactive disease for at least 30 days before the Screening Visit.
* Women must not be able to become pregnant (e.g., post menopausal for at least one year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. Women of childbearing potential must have a negative serum pregnancy test at the Screening Visit and be non-lactating.
* Geographic accessibility to the study site

Exclusion Criteria:

* History of known sensitivity or intolerability to lithium or to any other related compound
* Prior exposure to lithium within 90 days of the Screening Visit
* Exposure to any investigational agent within 30 days of the Screening Visit
* Participants who are malnourished, dehydrated or on a sodium-free diet will be excluded due to the potential side effects of lithium carbonate
* Use of digoxin or iodide salts \[e.g. calcium iodide, hydrogen iodide (hydriodic acid), iodide, iodinated glycerol (Organidin), iodine, potassium iodide (SSKI), and sodium iodide supplementation beyond table salt\]
* Presence of any of the following clinical conditions: Substance abuse within the past year; Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active malignancy or infectious disease; autoimmune deficiency syndrome (AIDS) or AIDS-related complex; Clinically active psoriasis within 30 days of the Screening Visit; Unstable psychiatric illness defined as psychosis (hallucinations or delusions) or untreated major depression within 90 days of the Screening Visit; Screening serum creatinine greater than or equal to 1.5 mg/dL (133 umol/L), thyroid stimulating hormone (TSH) \> 20% above the upper limit; Presence of any clinically significant conduction abnormalities on electrocardiogram (ECG); or Lactating or have a positive serum pregnancy test at the Screening Visit.

Answer: B