Amyotrophic lateral sclerosis (ALS) Nervous System Diseases
Conditions
Interventions
The EXPERTS-ALS protocol describes an overarching trial design to evaluate the effect of candidate drugs on blood NFL levels in patients with ALS receiving usual standard of care. The protocol is deli
? participant randomisation between only those treatment arms that are not believed by the enrolling doctor to be contraindicated (e.g., by particular co-morbid conditions or concomitant medications)
and
? treatment arms to be added or removed according to the emerging evidence from within the trial.
The current treatment arms are metformin, nifedipine and ropinirole.
Metformin: Where possible,
Sponsors
Sheffield Teaching Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Diagnosis of ALS according to Gold Coast criteria. 2. Age at least 18 years at the time of consent. 3. ENCALS prognosis risk score of -6.0 to -2.0 as calculated from the results of the screening visit. 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 (see protocol Section 5.8 and IMP-specific appendices for details). 7. Persons of childbearing potential must have a negative pregnancy test prior to randomisation.
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 14/03/2025: 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) which is known to independently raise 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. Refer to IMP-specific appendices for details. 6. Use of non-invasive ventilation >22 hr/day or invasive ventilation. 7. Pregnant or breastfeeding 8. Unable to comply with trial procedures. _____ Previous exclusion criteria: 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) which is known to independently raise NFL levels. 3. Participation 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. Refer to IMP-specific appendices for details. 6. Use of non-invasive ventilation >22 hr/day or tracheostomy ventilation. 7. Pregnant or breastfeeding 8. Unable to comply with trial procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in blood neurofilament light chain (NFL) levels measured using automated immunoassay analysed via the SIMOA HD-X instrument (Quanterix) from baseline to weeks 18 and 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 14/03/2025: Secondary outcomes: 1. Change in daily functioning measured using the ALS revised functional rating scale (ALSFRS-R) score from baseline to weeks 12 and 24 2. Progression in the clinical stage by 1 stage or more measured using King’s staging system from baseline to week 24 3. Adverse events and serious adverse events measured using data recorded at each study visit during the trial Exploratory outcomes: 1. To explore survival at 12 months without non-invasive ventilation >22 hr/day or invasive ventilation, and compare it with the median prediction of survival without non-invasive ventilation >22 hr/day or invasive ventilation from the European Network for the Cure of ALS (ENCALS) survival prediction model. 2. Change in WHO Disability Assessment Schedule (WHODAS 2.0) and Quality of Life (WHOQOL-Bref) from baseline to 24 weeks (or early discontinuation of treatment) against a natural history cohort 3. In-person forced vital capacity (FVC) and peak cough flow (PCF), compared with remote FVC (rFVC) and remote PCF (rPCF) where readings are available within +/- 7 days of each other (FVC and PCF measured at screening, baseline, week 12 and week 24 post randomisation) _____ Previous secondary outcome measures: Secondary outcomes: 1. Change in daily functioning measured using the ALS revised functional rating scale (ALSFRS-R) score from baseline to weeks 12 and 24 2. Progression in the clinical stage by 1 stage or more measured using King’s staging system from baseline to week 24 3. Adverse events and serious adverse events measured using data recorded at each study visit during the trial Exploratory outcomes: 1. Survival without tracheostomy or non-invasive ventilation at 12 months, compared with the ENCALS median prediction of survival without tracheostomy or non-invasive ventilation 2. Change in WHO Disability Assessment Schedule (WHODAS 2.0) and Quality of Life (WHOQOL-Bref) from baseline to 24 weeks (or early | — |
Countries
England, Scotland, United Kingdom, Wales
Outcome results
None listed