Inclusion & Exclusion Criteria

This page details the eligibility criteria for the study and is designed for clinical staff already working on EXPERTS-ALS. 

If you are a person with ALS looking for information about participating, please view this page instead. 

1. Diagnosis of ALS according to Gold Coast criteria.

2. Age at least 18 at the time of consent.

3. TRICALS risk profile score of -6.0 to -2.0 as calculated from the results of the screening visit. The TRICALS risk score is a prognostic summary value of seven patient characteristics used for optimal patient selection for efficient outcomes.

4. Those taking riluzole must be on a stable dose for at least 30 days prior to the baseline visit or must have chosen not to take it for the study duration.

5. Must be able to be randomised to at least two of the open arms after reviewing contraindications, current medication and the IMP-specific eligibility criteria as detailed in the IMP-specific appendices.

6. Fertile persons must use adequate contraception if required by the IMPs .

7. Persons of childbearing potential must have a negative pregnancy test prior to randomisation.

1. Clinically significant history of unstable or severe cardiac, oncological, hepatic or renal disease or other medically significant illness which, in the opinion of the local investigator, is a contraindication to participation.

2. Presence of an active disorder (other than ALS) or currently taking a drug which is known to independently alter NFL levels.

3. Treatment with IMP in any other investigational drug trial within 30 days prior to screening. 

4. Pre-existing use of current EXPERTS-ALS IMPs or drugs in the same class as current EXPERTS-ALS IMPs that would result in the patient not being able to be randomised between a minimum of two arms. 

5. Contraindications to IMPs that would result in the patient not being able to be randomised between a minimum of two arms. 

6. Use of non-invasive ventilation >22 hr/day or invasive ventilation.

7. Pregnant or breastfeeding.

8. Unable to comply with trial procedures.

Pre-existing diabetes is an exclusion for the metformin arm in this study. 

Other exclusions are as per the SmPC:

• Hypersensitivity to metformin hydrochloride or to any of the excipients

• Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis)

• Diabetic pre-coma

• Severe renal failure (eGFR <30 mL/min)

• Acute conditions with the potential to alter renal function, such as dehydration, severe infection, shock

• Disease which may cause tissue hypoxia (especially acute disease, or worsening chronic disease) such as decompensated heart failure, respiratory failure, recent myocardial infarction, shock

• Hepatic insufficiency, acute alcohol intoxication, alcoholism

There is no data regarding nifedipine administration in swallowing difficulties. Patients who are unable to swallow and cannot have medications via gastrostomy or equivalent will not be eligible for the nifedipine arm of this study.

Other exclusion criteria are as per the SmPC:

• Known hypersensitivity to nifedipine, other dihydropyridines because of the theoretical risk of cross reactivity or to any of the excipients

• Nursing individuals or those who are or may become pregnant

• Patients with clinically significant aortic stenosis, cardiogenic shock, unstable angina, or during or within one month of a myocardial infarction

• Inflammatory bowel disease, Crohn’s disease or with a history of gastrointestinal obstruction, oesophageal obstruction or with decreased diameter of the gastrointestinal lumen

• Hepatic impairment

• Malignant hypertension

• Patients with a Kock pouch (ileostomy after proctocolectomy)

• Concomitant treatment with rifampicin

• Acute porphyria

Presence or history of any psychotic disorder is an exclusion for the ropinirole arm in this study.

Other exclusion criteria are as per SmPC:

• Hypersensitivity to the active substance or to any of the excipients

• Severe renal impairment (creatinine clearance <30ml/min) without regular haemodialysis

• Hepatic impairment