Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Double-Blind, Placebo-Controlled, Study to Investigate the Safety and Efficacy of Lithium in Combination With Riluzole in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
Brief Summary: The purpose of this study is to compare the effectiveness of lithium combined with riluzole to riluzole combined with placebo in people with amyotrophic lateral sclerosis.


Options:
A: 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.
B: 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)
C: 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
D: To be eligible for enrollment in this study, subjects must meet the following eligibility criteria within fourteen days prior to randomization:

Inclusion criteria:

* A clinical diagnosis of laboratory-supported probable, probable or definite ALS, according to modified EL Escorial criteria.
* FVC greater or equal to 75% of predicted.
* Onset of weakness within 3 years prior to enrollment.
* If patients are receiving riluzole they must be on a stable dose for at least the past thirty days.
* Women of childbearing age must be non-lactating and surgically sterile or using an effective method of birth control and have a negative pregnancy test (adequate birth control includes use of intra-uterine device or oral contraceptives plus a barrier method, e.g. condom, diaphragm).
* Willing and able to give signed informed consent that has been approved by your Institutional Review Board (IRB).

Exclusion criteria:

* Requirement for tracheotomy ventilation (or non-invasive ventilation \> 23 hours/day).
* Diagnosis of other neurodegenerative diseases (Parkinson's disease, Alzheimer's disease, etc).
* FVC \< 75% of predicted.
* A clinically significant history of unstable medical illness (unstable angina, advanced cancer, etc) over the last 30 days.
* History of renal disease (screening creatinine greater than 1.5).
* History of liver disease (screening alanine aminotransferase greater than 3 times the upper limit of normal).
* History of hematologic disease (screening white blood cell count less than 3,800/mm3).
* History of system lupus erythematosis (or screening ANA of 1:160 or greater).
* Treatment with any medications that may cause lupus-like symptoms within 4 weeks of baseline visit (e.g. procainamide, hydralazine).
* History of vestibular disease (excluding benign position vertigo).
* Pregnancy or lactation.
* Allergy to tetracycline antibiotics.
* Use of minocycline within thirty days of enrollment (baseline visit).
* Use of anti-epileptic medications other than gabapentin.
* Limited mental capacity rendering the subject unable to provide written informed consent or comply with evaluation procedures.
* History of recent alcohol or drug abuse or noncompliance with treatment or other experimental protocols.
* Use of any investigational drug within the past 30 days (Creatine, Vioxx, Celebrex, Topiramate).
* Women with the potential to become pregnant who are not practicing effective birth control.

Answer: A