Amyotrophic Lateral SclerosisPhase 3NCT06008249
Platform Trial to Assess the Efficacy of Multiple Drugs in Amyotrophic Lateral Sclerosis (ALS)
A Phase 3 study testing Lithium Carbonate 400 MG in people with Amyotrophic Lateral Sclerosis, run by Stichting TRICALS Foundation at 13 sites in 6 countries.
Trial summary
The objective of this phase III, placebo-controlled platform study is to investigate the efficacy of drugs for patients with ALS (Amyotrophic lateral sclerosis). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Lithium Carbonate 400 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 13 sitesin 6 countries
- Study dates
- 9 Aug 2021to 1 Sep 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 18 years at the time of screening.
- Diagnosis of ALS according to the revised El Escorial criteria (possible, probable-laboratory supported, probable or definite).
- Capable of providing informed consent and complying with trial procedures, including randomization to sub-studies.
- TRICALS risk profile > -6.0 and < -2.0 **
- The use of riluzole will be permitted during the study. Subjects taking riluzole must be on a stable dose for at least 30 days prior to the baseline visit, or stopped taking riluzole at least 30 days prior to the baseline visit.
- Women of childbearing potential* must have a negative pregnancy test at baseline and be non-lactating.
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- Men must agree to practice contraception for the duration of the trial and for at least 3 months after last dose of study drug.
- Men must not plan to father a child or to provide sperm for donation for the duration of the trial and 3 months after the last dose of study drug.
- Women must not be able to become pregnant (e.g. post-menopausal***, surgically sterile or using effective birth control methods) for the duration of the study. Effective contraceptives are defined as having a failure rate of less than 1% per year when used consistently and correctly and, when applicable, in accordance with the product label, including: abstinence, hormonal contraception, intrauterine device in place for ≥ 3 months Appendix 1). Women of childbearing potential must have a negative pregnancy test at baseline, and be non-lactating. Women who are pregnant or are actively seeking to become pregnant, and women of reproductive potential who are not using effective contraceptives are excluded.
Who cannot join
- 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
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- 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.
- Lithium carbonate study-specific exclusion criteria:
- 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
Trial locations and contacts
13 sites in 6 countries.
13 sites in 6 countries
Australia6 sites
Flinders Medical Centre
Adelaide, SA 5042
Royal Brisbane and Women's Hospital
Brisbane, QLD 4029
Calvary Health Care Bethlehem
Parkdale, VIC 3195
Perron Institute
Perth, WA 6009
The University of Sydney (Royal prince Alfred hospital)
Sydney, NSW 2050
Concord hospital Sydney
Sydney, NSW 2139
United Kingdom3 sites
King's College Hospital
London, SE5 9RS
University College London Hospital NHS
London, WC1N 3BG
University Hospitals of North Midlands NHS Trust
Stoke-on-Trent, ST4 6QG
Netherlands1 site
University Medical Center Utrecht
Utrecht, Utrecht, 3584 CX
About this study
Official title: A Multi-arm, Adaptive, Group-sequential Trial NETwork to Evaluate Drug Efficacy in Patients With Amyotrophic Lateral Sclerosis (ALS)
The objective of this phase III, placebo-controlled platform study is to investigate the efficacy of drugs for patients with ALS (Amyotrophic lateral sclerosis).
Read the detailed description
This study uses an innovative multi-arm, adaptive trial design to investigate the efficacy of multiple treatments simultaneously. Currently one study-arm is active, investigating the efficacy and safety of lithium carbonate versus placebo in patients with ALS. Only patients with a specific UNC13A genotype (approximately 1 in 6 ALS patients) are eligible to participate.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Lithium Carbonate 400 MG
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lithium Carbonate 400 MGDrug
Lithium carbonate vs placebo (2:1)
| Study group | Role | What they receive |
|---|---|---|
| Lithium carbonate | Experimental | Lithium carbonate 400 mg capsules will be taken once daily, starting with one capsule (400 mg daily) initially titrated up to two or three capsules daily, depending on blood lithium levels. The target range for the lithium plasma level will be between ≥0.4 mmol/l and ≤ 0.8 mmol/l. Maximum duration is 24 months. Receives: Drug: Lithium Carbonate 400 MG |
| Placebo | Placebo comparator | Patients start with 1 capsule to be taken once daily, with subsequent sham dose adjustments made to patients on placebo to maintain blinding in clinical sites. Receives: Drug: Lithium Carbonate 400 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival, defined as time to death from any cause or respiratory insufficiency (DRI; defined as tracheostomy or the use of non-invasive ventilation for ≥22 h per day for ≥10 consecutive days)
A tracheostomy for ventilation is meant here
Measured: endpoint or 24 months
Secondary outcomes (11)
Composite endpoint evaluating daily functioning and survival based on the joint model framework of survival and longitudinal ALSFRS-R total scores
The ALSFRS-R (Amyotrophic Lateral Sclerosis Rating Scale-revised) is a 12 item participant self-report measure that monitors ALS disease progression, where a higher score reflects a better outcome.
Measured: endpoint or 24 months
Daily functioning, defined as mean change from baseline in ALSFRS-R total score.
The ALSFRS-R (Amyotrophic Lateral Sclerosis Rating Scale-revised) is a 12 item participant self-report measure that monitors ALS disease progression, where a higher score reflects a better outcome.
Measured: endpoint or 24 months
Respiratory function, defined as mean change from baseline in SVC (%predicted of normal according to the GLI-2012 reference standard)
Slow vital capacity (SVC) is measured in litres, and as a % of predicted. A higher score reflects a better outcome.
Measured: endpoint or 24 months
Quality of life, defined as change from baseline on the EQ-5D Visual Analogue Scale (single-item scale)
The EQ-5D-5L (EuroQol 5 Dimension 5 Level) questionnaire is a standardised measure of health-related Quality of Life, using a Visual Analogue Scale. A higher score relates to a better outcome
Measured: endpoint or 24 months
Quality of life, defined as change from baseline on the EQ-5D
The EQ-5D-5L (EuroQol 5 Dimension 5 Level) questionnaire is a standardised measure of health-related Quality of Life. A lower score relates to a better outcome
Measured: endpoint or 24 months
Neuropsychological status, defined as change from baseline on the ECAS
ECAS (Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen) is a multidomain assessment questionnaire used in ALS to assess cognitive and behavioural changes where a higher score relates to a better outcome.
Measured: endpoint or 24 months
Neuropsychological status, defined as change from baseline on the ALS-FTD-Q.
ALS-FTD-Q (Amyotrophic Lateral Sclerosis-Frontotemporal Dementia-Questionnaire) is a validated instrument for the screening of behavioral disturbances in ALS.
Measured: endpoint or 24 months
Clinical disease stage, defined as mean time spent in each stage of the King's and ALS Milano-Torino staging systems.
The King's Staging Scale is a clinical staging system defining four stages of ALS assessed by way of a semi-structured interview with the participant.
Measured: endpoint or 24 months
Change from baseline in laboratory parameters: Urinary P75ECD (ectodomain of neurotrophin receptor p75), Neurofilament light and heavy chain, Plasma creatinine
Plasma creatinine is assessed to monitor kidney function
Measured: endpoint or 24 months
Tolerability defined as time-to-discontinuation of assigned treatment since randomization
the number of participants who discontinue study medication will be assessed to assess tolerability
Measured: endpoint or 24 months
Safety based on the safety assessments including neurological examinations, clinical laboratory evaluations, vital signs and frequency of adverse events (AEs) or serious adverse events (SAEs).
(S)AEs will be categorized according to the Common Terminology Criteria for Adverse Events and will be rated for severity and association with study drug.
Measured: endpoint or 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2023
- Study start9 Aug 2021
- Primary completion1 Sep 2025
- Study completion1 Sep 2025
Why it stopped: The planned interim analysis showed no survival benefit of taking the drug when compared with placebo.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomised in a 2:1 ratio to receive either lithium carbonate or placebo
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stichting TRICALS Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- Fight MND, Research Foundation Flanders, MNDA, Thierry Latran Foundation, Ulla-Carin Lindquist Foundation, Luzon Foundation, Alan Davidson Foundation, My name'5 Doddie Foundation, Stichting ALS Nederland
- Responsible party
- Sponsor
- Investigators
- Leonard Van den Berg, MD, Study chair, TRICALS Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06008249
- Sponsor's protocol ID
- MAGNET
- Status last verified
- May 2026
- First submitted
- 14 Aug 2023
- Last updated
- 13 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Pending on privacy regulations.
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-arm, Adaptive, Group-sequential Trial NETwork to Evaluate Drug Efficacy in Patients With Amyotrophic Lateral Sclerosis (ALS)
- ClinicalTrials.gov ID
- NCT06008249
- Acronym / sponsor ID
- MAGNET
- Conditions
- Amyotrophic Lateral Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The planned interim analysis showed no survival benefit of taking the drug when compared with placebo.
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Stichting TRICALS FoundationUniversity, hospital or other
- Collaborators
- Fight MND, Research Foundation Flanders, MNDA, Thierry Latran Foundation, Ulla-Carin Lindquist Foundation, Luzon Foundation, Alan Davidson Foundation, My name'5 Doddie Foundation, Stichting ALS Nederland
- Study start
- 9 Aug 2021 (actual)
- Primary completion
- 1 Sep 2025 (actual)
- Study completion
- 1 Sep 2025 (actual)
- First posted
- 23 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this phase III, placebo-controlled platform study is to investigate the efficacy of drugs for patients with ALS (Amyotrophic lateral sclerosis).
Detailed description
This study uses an innovative multi-arm, adaptive trial design to investigate the efficacy of multiple treatments simultaneously. Currently one study-arm is active, investigating the efficacy and safety of lithium carbonate versus placebo in patients with ALS. Only patients with a specific UNC13A genotype (approximately 1 in 6 ALS patients) are eligible to participate.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Participants will be randomised in a 2:1 ratio to receive either lithium carbonate or placebo
| Arm | Type | Receives |
|---|---|---|
| Lithium carbonate | Experimental | Drug: Lithium Carbonate 400 MGLithium carbonate 400 mg capsules will be taken once daily, starting with one capsule (400 mg daily) initially titrated up to two or three capsules daily, depending on blood lithium levels. The target range for the lithium plasma level will be between ≥0.4 mmol/l and ≤ 0.8 mmol/l. Maximum duration is 24 months. |
| Placebo | Placebo comparator | Drug: Lithium Carbonate 400 MGPatients start with 1 capsule to be taken once daily, with subsequent sham dose adjustments made to patients on placebo to maintain blinding in clinical sites. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- ≥ 18 years at the time of screening.
- Diagnosis of ALS according to the revised El Escorial criteria (possible, probable-laboratory supported, probable or definite).
- Capable of providing informed consent and complying with trial procedures, including randomization to sub-studies.
- TRICALS risk profile > -6.0 and < -2.0 **
- The use of riluzole will be permitted during the study. Subjects taking riluzole must be on a stable dose for at least 30 days prior to the baseline visit, or stopped taking riluzole at least 30 days prior to the baseline visit.
Key exclusion criteria (27 listed)
- Laboratory Criteria at baseline:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lithium Carbonate 400 MGLithium carbonate vs placebo (2:1) | Drug | Lithium carbonate, Placebo |
Primary outcome
Overall survival, defined as time to death from any cause or respiratory insufficiency (DRI; defined as tracheostomy or the use of non-invasive ventilation for ≥22 h per day for ≥10 consecutive days)
Time frame: endpoint or 24 months
A tracheostomy for ventilation is meant here
11 secondary outcomes
Composite endpoint evaluating daily functioning and survival based on the joint model framework of survival and longitudinal ALSFRS-R total scores
Time frame: endpoint or 24 months
Daily functioning, defined as mean change from baseline in ALSFRS-R total score.
Time frame: endpoint or 24 months
Respiratory function, defined as mean change from baseline in SVC (%predicted of normal according to the GLI-2012 reference standard)
Time frame: endpoint or 24 months
Quality of life, defined as change from baseline on the EQ-5D Visual Analogue Scale (single-item scale)
Time frame: endpoint or 24 months
Quality of life, defined as change from baseline on the EQ-5D
Time frame: endpoint or 24 months
Neuropsychological status, defined as change from baseline on the ECAS
Time frame: endpoint or 24 months
Neuropsychological status, defined as change from baseline on the ALS-FTD-Q.
Time frame: endpoint or 24 months
Clinical disease stage, defined as mean time spent in each stage of the King's and ALS Milano-Torino staging systems.
Time frame: endpoint or 24 months
Change from baseline in laboratory parameters: Urinary P75ECD (ectodomain of neurotrophin receptor p75), Neurofilament light and heavy chain, Plasma creatinine
Time frame: endpoint or 24 months
Tolerability defined as time-to-discontinuation of assigned treatment since randomization
Time frame: endpoint or 24 months
Safety based on the safety assessments including neurological examinations, clinical laboratory evaluations, vital signs and frequency of adverse events (AEs) or serious adverse events (SAEs).
Time frame: endpoint or 24 months
Results and safety
The study was stopped early (reason given: The planned interim analysis showed no survival benefit of taking the drug when compared with placebo.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2026.
- Individual participant dataSharing planned: Undecided. Pending on privacy regulations.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leonard Van den Berg, MD study chair
TRICALS Foundation
13 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lithium Carbonate 400 MG in people with Amyotrophic Lateral Sclerosis, run by Stichting TRICALS Foundation at 13 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Australia, United Kingdom, Belgium, Netherlands, Spain and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The planned interim analysis showed no survival benefit of taking the drug when compared with placebo.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival, defined as time to death from any cause or respiratory insufficiency (DRI; defined as tracheostomy or the use of non-invasive ventilation for ≥22 h per day for ≥10 consecutive days) (time frame: endpoint or 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2026.