Platform Trial to Assess the Efficacy of Multiple Drugs in Amyotrophic Lateral Sclerosis (ALS)

Exclusion Criteria26

• Laboratory Criteria at baseline:
• ALT (alanine transaminase) ≥ 5 times upper limit of normal (ULN)
• AST (aspartate aminotransferase) ≥ 3 times ULN
• Bilirubin ≥ 1.5 times ULN
• Estimated glomerular filtration rate (eGFR) \< 50 mL / min / 1.73 m2 based on Cystatin C, if not available eGFR can also be calculated based on creatinine clearance.
• Platelet concentration of \< 100 x109 per L
• Absolute neutrophil count of \< 1x109 per L
• Haemoglobin \< 100 g/L (\<6.2 mmol/L)
• Amylase \& lipase ≥ 2 times ULN (suspected pancreatitis)
• Lactate ≥ 2 times ULN (suspected lactate acidosis)
• Moderate to severe hepatic impairment according to Child-Pugh classification (Class B or higher; score ≥ 7). Child-Pugh classification is based on bilirubin, albumin, International Normalized Ratio (INR) and presence of encephalopathy or ascites.
• Participation in any other investigational drug trial or using investigational drug (within 30 days prior to screening).
• Hypothyroidism unresponsive to thyroid hormone supplementation.
• Subjects using non-invasive ventilation (NIV, ≥22 h per day) or having a tracheostomy.
• Subjects taking edaravone within 30 days prior to screening. Edaravone is approved by the FDA, but remains an investigational product in Europe and Australia.
• Clinically significant history of unstable or severe cardiac (e.g. congestive heart failure, coronary insufficiency and arrhythmias), oncological, hepatic or renal disease, neuromuscular diseases, significant pulmonary disorder or other medically significant illness.
• Drug or alcohol abuse.
• Unstable psychiatric illness defined as psychosis or untreated major depression within 90 days of the screening visit. This exclusion criterion is based on a prior psychiatric diagnosis that is unstable as determined by the subject's treating Psychiatrist.
• Presence of frontotemporal dementia which prevents informed consent.
• Patients heterozygous or homozygous for the A-allele of rs12608932 (UNC13A)
• Known allergy or hypersensitivity to lithium, or its excipients, or to the components of the placebo.
• Brain injury with posttraumatic epilepsy or neurologic deficit, excluding a concussion in the medical history. Brain infarction is an exclusion criterion, a transient ischemic attack is not.
• Addison disease.
• Patients with the following co-medication: antipsychotics, digoxin and calcium antagonists, carbamazepine, methyldopa, verapamil and diltiazem.
• Brugada Syndrome or family history of Brugada Syndrome.
• Plasma sodium \<120 mmol/L